[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"National Institute of Allergy and Infectious Diseases (NIAID)\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":645},{"pageToken":4,"total":5,"offset":6,"count":7,"results":8},null,168,0,25,[9,50,89,119,149,173,198,227,249,273,294,319,343,366,388,415,440,462,487,512,543,563,583,603,625],{"id":10,"slug":11,"hasResults":12,"nctId":13,"briefTitle":14,"officialTitle":15,"acronym":4,"eligibilityCriteria":16,"healthyVolunteers":12,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":27,"conditions":28,"keywords":34,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":39,"startDateStruct":42,"completionDateStruct":44,"leadSponsor":46,"locationsCount":49},"100652704","phase-1-base-edited-hematopoietic-stemprogenitor-cell-gene-therapy-for-treatment-of-cxcr4-whim-100652704",false,"NCT07775313","Base-Edited Hematopoietic Stem\u002FProgenitor Cell Gene Therapy for Treatment of CXCR4-WHIM","Phase 1\u002F2 Base-Edited Hematopoietic Stem\u002FProgenitor Cell Gene Therapy for Treatment of CXCR4-WHIM","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Aged \\>= 3 years and weighing \\>=15 kg.\n* Confirmed CXCR c.1000C\\>T, pR334X mutation.\n* Ability to undergo apheresis for stem cell collection.\n* Medical lab data (historical) of neutropenia, or B cell dysfunction (low or absent IgG levels, or on IV gamma globulin.\n* Expected survival of at least 120 days.\n* Must be willing to have blood and tissue samples stored.\n* Participants of reproductive potential must agree to consistently use effective contraception from start of busulfan conditioning through at least one-year post-treatment. Acceptable forms of contraception are:\n\n  * Hormonal contraception in continuously effective use.\n  * Male or female condom with spermicide as indicated.\n  * Diaphragm or cervical cap in consistent and effective pattern of use with a spermicide.\n  * Intrauterine device in-situ\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Acute onset infection as indicated by symptoms such as persistent fevers, or imaging (new pneumonia on CT for example), isolated pathogen and requiring medical intervention.\n* Severe liver dysfunction with transaminases \\> 6 fold upper limit will be excluded until approval by hepatology consult who will provide mitigating plans for liver protection.\n* Renal dysfunction-serum creatinine \\>3.0 x ULN.\n* Coagulation dysfunction- Prothrombin INR or Partial thromboplastin time \\>2 x ULN (patients on controlled anticoagulation agents will not be excluded for therapeutic levels).\n* Known hypersensitivity to busulfan or any component of the product.\n* Contraindications for administration of busulfan, including but not limited to: hypersensitivity, chronic lymphocytic leukemia, acute leukemia in blastic crisis, pregnancy, or lactation.\n* Childhood malignancy (occurring before 18 years of age) in the participant or a first degree relative, or previously diagnosed known genotype of the participant conferring a predisposition to cancer unless approved by the with appropriate consultants and approved by the study PI (no DNA or other testing for cancer predisposition genes will be performed as part of the screen for this protocol).\n* Any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the participant, or would preclude the participant from successful study completion.","ALL","3 Years","75 Years",{"count":21,"type":22},10,"ESTIMATED","INTERVENTIONAL",[25,26],"PHASE1","PHASE2","Background:\n\nWarts, hypogammaglobulinemia, infections and myelokathexis syndrome (WHIMs) is a rare disorder that affects the immune system. People with WHIMs can have severe infections all over their body. WHIMs is caused by a mutation in the CXCR4 gene. Treatment with drugs can help control the infections but does not cure the disorder. Researchers want to try a treatment where they collect stem cells from a person with WHIMS, use base-editing to replace the bad gene with a healthy version, and return the new cells to the person. This could cure WHIMs.\n\nObjective:\n\nTo test a treatment using base-edited stem cells in people with WHIMs.\n\nEligibility:\n\nPeople aged 3 years and older with WHIMs.\n\nDesign:\n\nThe study has 4 stages.\n\nStage 1: Screening. Participants will be screened at 1 or more visits. They will have a physical exam with blood tests. A sample of tissue and fluid (biopsy) will be taken from the bone marrow in the hip.\n\nStage 2: Apheresis. Blood will be taken from the body through a needle; the blood will pass through a machine that separates out the stem cells. The remaining blood will be returned to the body through a different needle. The collected stem cells will undergo gene editing.\n\nStage 3: Treatment. Participants will stay in the hospital for about 4 weeks. They will receive 3 drugs to prepare their body for the procedure. Then the edited stem cells will be returned to their bloodstream. They will stay in the hospital until they recover.\n\nStage 4: Follow-up. Participants will have 8 follow-up visits over 5 years. Long-term visits will continue for 15 years.",[29,30,31,32,33],"WHIM","Warts","Hypogammaglobulinemia","Immunodeficiency","Myelokathexis",[35,36],"Gene Editing","base editing","NOT_YET_RECRUITING","2026-08-20",{"date":40,"type":41},"2026-08-21","ACTUAL",{"date":43,"type":22},"2026-08-26",{"date":45,"type":22},"2033-12-31",{"name":47,"class":48},"National Institute of Allergy and Infectious Diseases (NIAID)","NIH",1,{"id":51,"slug":52,"hasResults":12,"nctId":53,"briefTitle":54,"officialTitle":55,"acronym":4,"eligibilityCriteria":56,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":59,"enrollmentInfo":60,"targetDuration":4,"studyType":23,"phases":62,"briefSummary":63,"conditions":64,"keywords":66,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":83,"startDateStruct":84,"completionDateStruct":86,"leadSponsor":88,"locationsCount":49},"100645476","phase-1-safety-and-immunogenicity-of-chimeric-hemagglutinin-mrna-vaccine-candidates-100645476","NCT07703514","Safety and Immunogenicity of Chimeric Hemagglutinin mRNA Vaccine Candidates","A Phase 1, Randomized, Controlled, Dose-Ranging Study to Evaluate the Safety and Immunogenicity of Influenza A Group 1 and Influenza A Group 2 mRNA Chimeric Hemagglutinin Vaccine Candidates Alone and in Combination in Healthy Adults.","Inclusion Criteria:\n\n1. Provision of signed and dated informed consent form before the initiation of any study procedures.\n2. Stated willingness to comply with all study procedures and availability for the duration of the study.\n3. Non-pregnant healthy adults, aged 18 to 59 years of age, inclusive, at the time of enrollment.\n4. In good general health as evidenced by medical history or diagnosed with stable chronic medical or psychiatric diagnoses or conditions.\\*\n\n   \\*As determined by medical history, medications use, and physical examination to evaluate ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would not affect the assessment of the safety of participants or the immunogenicity of study products. These medical diagnoses or conditions should be stable for the last 60 days (no hospitalizations, emergency room \\[ER\\] or urgent care for the condition \\[excluding musculoskeletal conditions\\], or invasive medical procedure and no adverse symptoms that need medical intervention such as medication change\u002Fsupplemental oxygen). This includes no change in chronic prescription medication or dose as a result of new symptoms or deterioration of the condition or disease being treated in the 30 days prior to enrollment. Any prescription change that is due to a change of health care provider, insurance company, etc., or that is done for financial reasons, as long as in the same class of medication, will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as-needed (prn) medications if, in the opinion of the site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity, and do not indicate a worsening or treatment of continued symptoms of medical diagnosis or condition. Note: Low-dose topical corticosteroids as outlined in the Exclusion Criteria as well as herbals, vitamins, and supplements are permitted.\n5. Oral temperature is less than 100.4 degrees Fahrenheit\\*.\n\n   \\*Inclusion requirement at enrollment and prior to study product administration.\n6. Heart rate (HR) is 55 to 100 beats per minute, inclusive\\*. \\*Screening heart rate values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.\n7. Systolic blood pressure is 90 to 140 mmHg, inclusive\\*.\n\n   \\*Screening systolic blood pressure values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.\n8. Diastolic blood pressure is 55 to 90 mmHg, inclusive\\*. \\*Screening diastolic blood pressure values in the normal range or with grade 1 abnormalities deemed not clinically significant by the site PI or designated clinician licensed to make medical diagnoses and listed on Form FDA 1572 are considered acceptable.\n9. BMI between 18 kilograms\u002Fsquare meter (kg\u002Fm\\^2) (inclusive) and \\\u003C35 kg\u002Fm\\^2 at screening\n10. Females of childbearing potential\\* must agree to true abstinence\\*\\* or use at least 1 acceptable primary form of contraception\\*\\*\\*,\\*\\*\\*\\*\n\n    * Not of childbearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, salpingectomy, or Essure® placement with history of documented radiological confirmation test at least 90 days after the procedure).\n\n      \\*\\*True abstinence is 100% of the time, no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, post-ovulation methods\\] and withdrawal are not acceptable methods of contraception).\n\n      \\*\\*\\*Acceptable forms of primary contraception include monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the study product, tubal ligation, intrauterine devices, birth control pills, and injectable\u002Fimplantable\u002Finsertable hormonal birth control products\n\n      \\*\\*\\*\\*Must use at least one acceptable primary form of contraception for at least 30 days before screening and agreement to use such a method during study participation and for an additional 30 days after the end of last study product administration.\n11. Females of reproductive potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test within 24 hours before the study product administration.\n12. Must agree to have samples collected for secondary research.\n\nExclusion Criteria:\n\n1. A history of any medical disease or condition that, in the opinion of the site PI or appropriate sub-investigator, is a contraindication to study participation\\*.\n\n   \\*Including acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial.\n2. A history of any known or suspected immunosuppressive condition, acquired or congenital, or autoimmune conditions as determined by history and\u002For physical examination.\n3. A history of known active or recently active (12 months) neoplastic disease or a history of any hematologic malignancy. (Non-melanoma, treated, skin cancers are permitted.)\n4. A history of myocarditis or pericarditis.\n5. A history of Guillain-Barré Syndrome.\n6. Receipt of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years before study product administration.\n7. Current pregnancy or breastfeeding.\n8. Known allergic reactions to components of the investigational products or seasonal influenza vaccine.\n9. Febrile illness or other acute illness\\* within 72 hours before the first study product administration.\n\n   \\*An acute illness that is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.\n10. Receipt of another experimental agent\\* or other intervention within 60 days before the first study product administration\\*\\*.\n\n    \\*Including vaccine, drug, biologic, device, blood product, or medication.\n\n    \\*\\*Other than from participation in this trial\n11. Any condition that, in the judgment of the investigator, precludes participation because it could affect participant safety.\n12. Has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody\\*, or HIV type 1 or 2 antibodies at screening.\n\n    \\*Persons testing positive for hepatitis C virus antibody with a history of treatment and a negative HCV viral load may be acceptable in the opinion of the PI or appropriate Sub-Investigator.\n13. Currently enrolled in or plans to participate in another clinical trial with an investigational agent\\*that will be received during the study-reporting period\\*\\*.\n\n    \\*Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or medication.\n\n    \\*\\*Approximately 10 months after the first study product administration.\n14. Has a history of hypersensitivity or severe allergic reaction\\* to any previous licensed or unlicensed influenza, mRNA, or LNP-containing vaccines.\n\n    \\*For example, anaphylaxis, generalized urticaria, angioedema, or other significant reactions.\n15. Chronic use (more than 14 continuous days) of any medications that may be associated with impaired immune responsiveness\\*.\n\n    \\*Including, but not limited to, systemic corticosteroids exceeding 10 mg\u002Fday of prednisone equivalent, allergy injections, immunoglobulin, interferon, immunomodulators, cytotoxic drugs, or other similar or toxic drugs during the preceding 6-month period before study product administration (Day 1). The use of low-dose topical, ophthalmic, inhaled, and intranasal steroid preparations will be permitted.\n16. Anticipating the need for immunosuppressive treatment within the next 6 months.\n17. Received immunoglobulins and\u002For any blood or blood products (except Rho D immunoglobulin) within the 4 months before the first study product administration.\n18. Plans to donate blood or blood products from screening through 90 days after dosing.\n19. Has any blood dyscrasias or significant disorder of coagulation.\n20. Has any chronic liver disease, including fatty liver.\n21. Has a history of alcohol abuse or other recreational drug (excluding cannabis) use within 6 months before the first study product administration.\n22. Has any abnormality or permanent body art (e.g., tattoo) that would interfere with the ability to observe local reactions at the injection site.\n23. Received or plans to receive a licensed, live vaccine within 4 weeks before first study product administration through 4 weeks after last study product administration.\n24. Received or plans to receive a licensed, inactivated vaccine within 2 weeks before first study product administration through 2 weeks after last study product administration.\n25. Received or plans to receive a seasonal influenza vaccine within 90 days before first study product administration through 90 days after last study product administration.\n26. Have a known history of confirmed influenza virus infection within the past 90 days.\n27. Have screening clinical laboratory examinations of grade 1 or above\\*.\n\n    \\*Grade 1 criteria for clinical laboratory (WBC count, hemoglobin, platelet count, creatinine, ALT, total bilirubin) may be acceptable if deemed not clinically significant by the site principal investigator (PI) or the study clinician listed on the delegation log.\n28. Has had a positive SARS-CoV-2 test (home or laboratory-based) within 7 days before the screening visit or during the period between screening and enrollment visits.",true,"18 Years","59 Years",{"count":61,"type":22},60,[25],"This is a Phase 1, randomized, controlled, dose-ranging clinical trial to assess the safety and immunogenicity of novel influenza A Group 1 and influenza A Group 2 mRNA chimeric hemagglutinin (HA) vaccine candidates given as intramuscular injections alone and in combination. A total of 60 healthy men and non-pregnant, non-breastfeeding women aged 18 through 59 years will be enrolled in one of 6 study arms. The 6 arms will consist of: 1) Sequential influenza A Group 1 mRNA chimeric hemagglutinin: cH8\u002F1 (25 µg) followed by cH5\u002F1 (25 µg), 2) Sequential influenza A Group 2 mRNA chimeric hemagglutinin: cH15\u002F3 (25 µg) followed by cH4\u002F3 (25 µg), 3) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8\u002F1 + cH15\u002F3 (25 µg) followed by cH5\u002F1 + cH4\u002F3 (25 µg), 4) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8\u002F1 + cH15\u002F3 (50 µg) followed by placebo, 5) A single dose of combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH5\u002F1 + cH4\u002F3 (50 µg) followed by placebo, 6) Sequential combined influenza A Group 1 and Group 2 mRNA chimeric hemagglutinin: cH8\u002F1 + cH15\u002F3 (50 µg) followed by cH5\u002F1 + cH4\u002F3 (50 µg). The primary objectives are to evaluate safety and immunogenicity: 1) To assess the safety and reactogenicity of one or two doses of monovalent or bivalent Group 1 and 2 study products and 2) To describe the Group 1 and 2 anti-HA stalk IgG antibody responses of one or two doses of monovalent or bivalent Group 1 and 2 study products by ELISA.",[65],"Influenza",[67,68,69,70,71,72,73,74,75,65,76,77,78,79,80,81,82],"cH15\u002F3 (WA79\u002FHK14)","cH4\u002F3 (CZ56\u002FHK14)","cH5\u002F1 (VN04\u002FCA09)","cH8\u002F1 (SW02\u002FCA09)","Chimeric Hemagglutinin","Double Blinded","Flu-CHAMPs","Healthy adults","Immunogenicity","Influenza A","mRNA","Phase 1","Placebo","Randomized","Safety","Vaccine",{"date":40,"type":41},{"date":85,"type":22},"2026-08-07",{"date":87,"type":22},"2027-04-12",{"name":47,"class":48},{"id":90,"slug":91,"hasResults":12,"nctId":92,"briefTitle":93,"officialTitle":93,"acronym":4,"eligibilityCriteria":94,"healthyVolunteers":12,"sex":17,"minAge":95,"maxAge":96,"enrollmentInfo":97,"targetDuration":4,"studyType":99,"phases":4,"briefSummary":100,"conditions":101,"keywords":105,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":114,"startDateStruct":115,"completionDateStruct":116,"leadSponsor":118,"locationsCount":49},"100645474","natural-history-of-trisomy-8-associated-autoinflammatory-disease-triad-and-related-disorders-100645474","NCT07683104","Natural History of Trisomy 8-Associated Autoinflammatory Disease (TRIAD) and Related Disorders","* INCLUSION CRITERIA:\n\nTo be eligible to participate in this study, an individual must meet the following criteria:\n\n1. Stated willingness to comply with study requirements.\n2. Aged \\\u003C= 99 (ability to be seen at NIH vs. remote visit may be determined by age and location).\n3. Willingness to allow storage of data and specimens for future research.\n\nAdditional Inclusion Criteria for Affected Participants\n\n1. Must have one of the following:\n\n   1. Trisomy 8 mosaicism verified by genetic testing (including but not limited to karyotype, fluorescence in situ hybridization \\[FISH\\], whole genome sequencing \\[WGS\\], whole exome sequencing \\[WES\\], or microarray), or\n   2. Inflammatory mucosal ulcerative disease clinically similar to TRIAD at the discretion of the principal investigator.\n2. Ability of participant or LAR to provide informed consent.\n\nAdditional Inclusion Criteria for Biological Relatives\n\n1. Be an unaffected biological relative of an affected participant.\n2. Ability to provide informed consent.\n3. Willingness to provide at least one biospecimen.\n\nEXCLUSION CRITERIA:\n\nIndividuals with any condition or who are taking any medications that, in the opinion of the investigator, contraindicates participation in the study will be excluded.\n\nCo-enrollment guidelines: Enrollment in this protocol does not preclude individuals from enrolling or participating in any other NIH protocols, including studies of investigational agents. Participants will be asked about their participation in other studies to ensure that blood draws do not exceed NIH limits for research protocols.","1 Day","99 Years",{"count":98,"type":22},750,"OBSERVATIONAL","Background:\n\nTrisomy 8 mosaicism is a genetic disorder that can increase inflammation in the body. Symptoms include fevers; sores or ulcers in the mouth, digestive tract, or genital area; skin rashes; problems in organs or tissues; and changes in bone marrow cells. Researchers want to conduct a natural history study to learn more about these symptoms and what causes them.\n\nObjective:\n\nTo gather data and samples from people with and without the trisomy 8 mosaicism.\n\nEligibility:\n\nPeople of any age with the trisomy 8 gene mosaicism. Their healthy relatives are also needed.\n\nDesign:\n\nAffected participants will have visits every 1 to 2 years for 30 years at NIH. Each visit will take 1 to 5 days and may be in-person or remote. With remote visits, participants may have a video call with the study team and samples may be sent to researchers by mail.\n\nParticipants may have these procedures:\n\nPhysical exam, with blood tests.\n\nTests of brain function and motor skills.\n\nSensory tests. Researchers will see how participants respond to sensations such as pinpricks, heat, cold, and pressure.\n\nMagnetic resonance imaging (MRI) scan of the brain and\u002For spine.\n\nX-ray of the spine.\n\nUltrasound test of heart function (echocardiogram).\n\nTissues samples (biopsies) collected from the skin, inside of the mouth, and bone marrow.\n\nSwabs to collect cells from the mouth, skin, and vagina.\n\nCollection of blood, stool, urine, saliva, hair, and fingernail samples.\n\nX-rays, MRI, and heart tests will be done only once. Other procedures may be repeated at each visit. All tests and procedures are voluntary.\n\nHealthy relatives who enroll will have a baseline visit and then follow-up visits as needed. They will have a physical exam. The inside of their mouth may be swabbed. Samples of blood, stool, urine, and saliva may be taken.",[102,103,104],"Trisomy 8 Mosaicism","Trisomy 8 Associated Autoinflammatory Disease","Mucosal Ulcerations",[106,107,108,109,110,111,112],"Genital Ulcers","Myelodysplastic Syndromes","Mucosal ulcerations","Recurrent fever","Oral aphthous ulcers","Autoinflammatory disease","Trisomy 8 mosaicism","RECRUITING",{"date":40,"type":41},{"date":43,"type":22},{"date":117,"type":22},"2056-06-01",{"name":47,"class":48},{"id":120,"slug":121,"hasResults":12,"nctId":122,"briefTitle":123,"officialTitle":124,"acronym":4,"eligibilityCriteria":125,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":126,"enrollmentInfo":127,"targetDuration":4,"studyType":23,"phases":129,"briefSummary":130,"conditions":131,"keywords":133,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":142,"startDateStruct":143,"completionDateStruct":145,"leadSponsor":147,"locationsCount":148},"100645446","phase-1-a-safety-reactogenicity-and-immunogenicity-trial-of-rvx-scpd9-booster-intranasal-covid-19-vaccine-100645446","NCT07703475","A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine","A Phase 1, Open-Label, Safety, Reactogenicity, and Immunogenicity Trial of RVX-sCPD9, a Live-Attenuated SARS-CoV-2, as a Booster Vaccine, Via the Intranasal Route in Previously Vaccinated Adults","Inclusion Criteria:\n\n1. Provides written informed consent before initiation of any study procedures.\n2. Able to understand and agree to comply with planned study procedures and be available for all study visits.\n3. Non-pregnant adults, 18 through 64 years of age at the time of study product administration.\n4. Participants of childbearing potential\\* must agree to use or have practiced true abstinence\\*\\* or use at least one acceptable primary form of contraception\\*\\*\\*.\n\n   \\*These criteria apply to females who are in a heterosexual relationship who are of childbearing potential. Not of childbearing potential include post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation\u002Fsalpingectomy).\n\n   \\*\\*True abstinence is 100% of the time, no sexual intercourse (penis enters the vagina). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods.\n\n   \\*\\*\\*Acceptable forms of primary contraception include a monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more before the participant's study product administration, intrauterine devices, birth control pills, and injectable\u002Fimplantable\u002Finsertable\u002Ftransdermal hormonal birth control products. Must have used at least one acceptable primary form of contraception for at least 30 days before study product administration and agree to continue at least one acceptable primary form of contraception through 60 days after study product administration.\n5. Participants of childbearing potential must have a negative urine pregnancy test at screening and within 24 hours before study product administration.\n6. In general good health\\*.\n\n   \\*As determined by medical history and physical examination, including vital signs, to evaluate acute or ongoing chronic medical diagnoses\u002Fconditions that have been present for at least 90 days, which would affect the assessment of the safety of participants. Chronic medical diagnoses\u002F conditions should be stable for the last 30 days (i.e., no hospitalizations, ER, or urgent care for the condition). This includes no change in chronic prescription medication, dose, or frequency due to deterioration of the chronic medical diagnosis\u002Fcondition 30 days before the study product administration. Any prescription change due to a change of health care provider, insurance company, etc., or done for financial reasons and in the same class of medication will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as-needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity.\n7. Receipt of a complete primary authorized or approved COVID-19 vaccine series and at least one booster\\* with the last vaccination at least 16 weeks before study product administration.\n\n   \\*Booster may be either homologous or heterologous to the primary vaccine series. It must be an FDA-authorized\u002Flicensed vaccine, though doses may have been received during a clinical trial (see MOP for further details).\n8. Clinical screening laboratory evaluations are within normal reference ranges or grade 1 with no clinical significance (NCS) per the investigator's discretion\\*.\n\n   \\*Laboratory evaluations include White Blood Cells \\[WBCs\\] with differential, hemoglobin \\[Hgb\\], platelets \\[PLTs\\], Alanine Transaminase \\[ALT\\], Aspartate Transaminase \\[AST\\], Creatinine \\[Cr\\], Alkaline Phosphatase \\[ALP\\], and Total Bilirubin \\[T. Bili\\]). Clinical laboratory evaluations that are below the site reference range, but not graded by the toxicology table, are not exclusionary unless deemed clinically significant by an investigator.\n9. Must agree to have samples stored for secondary research.\n\nExclusion Criteria:\n\n1. Positive SARS-CoV-2 PCR at screening.\n2. Abnormal vital signs (Grade 1 or higher)\\*.\n\n   \\*Grade 1 or higher is equivalent to: Systolic blood pressure (SBP) \\>\u002F= 141 mmHg or \\\u003C\u002F= 89 mmHg. Diastolic blood pressure (DBP) \\>\u002F= 91 mmHg. Heart rate (HR) is \\>\u002F= 101 beats per minute or \\\u003C\u002F= 54 beats per minute. Oral temperature \\>\u002F= 38.0 degrees Celsius (100.4 degrees Fahrenheit).\n3. Self-reported or medically documented SARS-CoV-2 infection (regardless of whether symptomatic or asymptomatic) within 16 weeks prior to study product administration.\n4. Participant who is pregnant or breastfeeding.\n5. Blood or plasma donation within 4 weeks before study product administration.\n6. Receipt of antibody or blood-derived products within 90 days before study product administration.\n7. Any self-reported or documented significant medical or psychiatric diseases\\* or any other condition that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation.\n\n   \\*Significant medical or psychiatric conditions include but are not limited to drug or alcohol abuse within 6 months of enrollment, significant kidney disease, liver disease, ongoing malignancy, or recent diagnosis of malignancy in the last five years, excluding treated basal and squamous cell carcinoma of the skin and cervical carcinoma in situ, which are allowed.\n8. Neurological conditions\\*.\n\n   \\*Including history of Bell's palsy, history of four or more migraine headaches in the past 12 months that interfered with normal daily activity or any migraine headache in the past 5 years that required emergency or inpatient medical care, epilepsy, seizures in the last 5 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease.\n9. History of significant respiratory disease currently requiring daily medications, history of asthma in the past 5 years, or any treatment of respiratory disease exacerbations in the last 5 years.\n10. History of cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), including any history of myocarditis, pericarditis, or uncontrolled cardiac arrhythmia.\n11. Any autoimmune disease, including hypothyroidism, without a defined non-autoimmune cause.\n12. Has an acute illness determined by the site PI or appropriate sub-investigator within 72 hours before study product administration\\*.\n\n    \\*An acute illness that is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.\n13. Has a positive test result for hepatitis B surface antigen, hepatitis C virus RNA (by reflex testing), or human immunodeficiency virus (HIV) antigen\u002Fantibody test at screening.\n14. Has any confirmed or suspected immunosuppressive or immunodeficient state such as asplenia, recurrent severe infections, and chronic\\* immunosuppressant medication within the past 6 months\\*\\*.\n\n    \\*Chronic means more than 14 continuous days.\n\n    \\*\\*Ophthalmic and topical steroids are allowed. See exclusion 19 for intranasal steroids.\n15. Has received any investigational study product within 60 days, or 5 half-lives, whichever is longer, before study product administration or is planning to receive one during the study.\n16. Has a history of hypersensitivity or severe allergic reaction\\* to any previous licensed or unlicensed vaccines or the candidate study product components\\*\\*.\n\n    \\*(e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction).\n    * See IB for study product formulation.\n17. Received or plans to receive licensed inactivated\u002Fsubunit vaccine within 14 days of study product administration or live vaccine within 28 days of study product administration.\n18. Plan to receive a COVID-19 booster vaccine within the 180 days following study product administration.\n19. Regular use of intranasal medications, including steroids, and sinus rinsing treatments\\*.\n\n    \\*Participants must have had no intranasal medication use for 30 days before study product administration and do not plan to use intranasal medications for 30 days after study product administration for medications other than steroids and for 6 months after study product administration for intranasal steroids (including over the counter (OTC) fluticasone). Participants should not use nasal irrigation or sinus rinsing treatments (e.g., Neti pots or saline washes) for 28 days after the study product administration and 7 days before study visits for the duration of the trial.\n20. Use of illicit intranasal drugs in the 5 years before study product administration or plans to use during the study.\n21. Current smoker (including cigarettes, marijuana, and vaping) or smoking within the prior 3 months.\n22. Planned international travel between study product administration and Day 29 visit.\n23. Any significant nasal or upper airway disease\\*.\n\n    \\*Including, but not limited to, being prone to epistaxis, has a history of inflammatory rhinitis (including allergic rhinitis) that requires daily medications, cochlear implants, head\u002Fneck radiation history, anosmia\u002Fdysosmia, and certain ear, nose and throat (ENT) conditions, including major anatomic nasopharyngeal abnormality or sinus polyp disease due to chronic sinusitis.\n24. Living with a person who has a condition that predisposes to high risk of severe COVID-19 or \\>\u002F=2 conditions that predisposes to increased risk of COVID-19 per IDSA guidelines.\n25. Healthcare workers with patient-facing responsibilities.\n26. Resides in or works in a nursing home or other skilled nursing facility.\n27. Allergy or contraindications to nirmatrelvir, ritonavir, or remdesivir.","64 Years",{"count":128,"type":22},80,[25],"This phase 1 clinical trial will evaluate the safety, reactogenicity, and immunogenicity of RVX-sCPD9, given Intranasally (IN), as a booster dose to previously vaccinated healthy adults. The study is designed as a non-randomized, open-label, dose-escalation clinical trial evaluating four dose levels of RVX-sCPD9 administered IN (10\\^2, 10\\^3, 10\\^4, 5 x 10\\^4 FFU). A sample size of 80 participants (20 participants in each cohort).\n\nThe primary objective is to evaluate the safety and reactogenicity of a single IN administration of 4 ascending dosages of RVX-sCPD9 in previously vaccinated healthy adults.",[132],"COVID -19",[134,135,136,137,138,139,78,140,141,82],"Boost","Boster","Coronavirus","COVID","Intranasal","Next Generation","RVX-sCPD9","SARS-CoV-2",{"date":40,"type":41},{"date":144,"type":22},"2026-08-15",{"date":146,"type":22},"2027-11-15",{"name":47,"class":48},4,{"id":150,"slug":151,"hasResults":12,"nctId":152,"briefTitle":153,"officialTitle":154,"acronym":4,"eligibilityCriteria":155,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":19,"enrollmentInfo":156,"targetDuration":4,"studyType":23,"phases":158,"briefSummary":159,"conditions":160,"keywords":162,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":167,"startDateStruct":168,"completionDateStruct":170,"leadSponsor":172,"locationsCount":4},"100641268","phase-1-a-safety-trial-to-evaluate-an-orally-ingested-yeast-modified-to-express-a-tetra-specific-anti-toxin-for-clostridioides-difficile-100641268","NCT07649096","A Safety Trial to Evaluate an Orally Ingested Yeast Modified to Express a Tetra-specific Anti-toxin for Clostridioides Difficile","A Phase 1 Trial to Evaluate an Orally Ingested Probiotic Yeast Genetically Modified to Express a Tetra-specific Anti-toxin for Clostridioides Difficile","Inclusion Criteria:\n\nTo be eligible to participate in Part A of this trial, an individual must meet all of the following criteria:\n\n1. Provides written informed consent prior to the initiation of any trial procedures.\n2. Is able to understand and agrees to comply with all planned trial procedures and be available for all study visits, including:\n\n   1. Receiving 28 days of blinded oral study product\n   2. Providing blood and self-collected stool samples\n3. Is a non-pregnant individual, aged 18-75 years, inclusive, at the time of enrollment.\n4. Has no more than 1 single Grade 1 screening laboratory abnormality that is not clinically significant. If the participant has more than 1 Grade 1 abnormality, it must be approved by the Division of Microbiology and Infectious Diseases \\[DMID\\] Medical Monitor (MM).\n5. Participants of childbearing potential: use of adequate contraception for at least 4 weeks prior to enrollment and agreement to use such a method during trial participation and for an additional 4 weeks after the last dose of blinded study product. Note: Definitions of participants of childbearing potential and adequate contraception are provided in Section 13.1.\n6. Agrees to refrain from ingestion of probiotics\\* or fermented foods\\*\\* from 7 days prior to study product administration, while on blinded study product, and through Day 36 (Visit 6).\n\n   \\*E.g., probiotic nutritional Lactobacillus or Bifidobacterium supplements, yogurt, kefir, any \"live and active culture\" nutritional product, etc.\n\n   \\*\\*E.g., kombucha, fermented pickled vegetables, etc.\n7. Has good health by medical history, vital signs, physical examination, and concomitant medication review\\*. Participants should be stable based on their condition over the last 3 months prior to enrollment.\n\n   \\*As defined by not requiring a change in therapy (including dose or frequency) or medical care for worsening disease for at least 3 months prior to enrollment. Vital signs must not meet Grade 1 or higher.\n8. Not using medications daily that may affect gut motility, gastric acidity, or baseline gut function\\* within 3 months of enrollment and through Day 36 (Visit 6).\n\n   \\*E.g., proton pump inhibitors, opioids, anti-diarrheal agents, anti-constipation agents, daily Over-the-counter \\[OTC\\] \"heartburn\" relief medications.\n9. Not using glucagon-like peptide-1 (GLP-1) receptor agonists within 6 weeks of enrollment.\n10. Any elective surgery (including dental) that required preoperative or postoperative antibiotics must have been completed at least 3 months prior to enrollment.\n11. No history of Clostridioides difficile infection \\[CDI\\] (suspected or proven), no recent hospital admissions (within 3 years), and no receipt of systemic antibiotics known to increase risk of CDI\\* (within 6 months).\n\n    \\*Systemic antibiotics that are known to increase the risk of CDI include lincosamides (e.g., clindamycin), monobactams (e.g., aztreonam), extended-spectrum penicillin combinations with beta-lactamase inhibitors (e.g., piperacillin-tazobactam), carbapenems (e.g., imipenem, meropenem, ertapenem), third generation or higher cephalosporins, and fluoroquinolones. Common oral antibiotics that would be allowable or are not known to significantly increase risk of CDI include amoxicillin, azithromycin, cephalexin, doxycycline, metronidazole, and trimethoprim\u002Fsulfamethoxazole.\n12. No history of other enteric infections or diarrheal illness within 3 months of enrollment.\n\nIn order to be eligible to participate in Part B of this trial, an individual must meet all of the following criteria:\n\n1. Provides written informed consent prior to the initiation of any trial procedures.\n2. Is able to understand and agrees to comply with all planned trial procedures and be available for all study visits, including:\n\n   1. Receiving 28 days of blinded oral study product\n   2. Providing blood and self-collected stool samples\n3. Is non-pregnant individual, aged 18-75 years, inclusive, at the time of enrollment.\n4. Has no more than 1 single Grade 1 hematology result and no more than 1 Grade 1 metabolic panel result. If the participant has more than 1 Grade 1 abnormality, it must be approved by the MM.\n5. Participants of childbearing potential: use of adequate contraception for at least 4 weeks prior to enrollment through 4 weeks after the last dose of blinded study product. Note: Definitions of participants of childbearing potential and adequate contraception are provided in Section 13.1.\n6. To rule out live microbial products and factors that may actively modulate the gut microbiome, participant agrees to refrain from ingestion of probiotics\\* or fermented foods\\*\\* from 7 days prior to study product administration, while on blinded study product, and through Day 36 (Visit 6).\n\n   \\* E.g., probiotic nutritional Lactobacillus or Bifidobacterium supplements, yogurt, kefir, any \"live and active culture\" nutritional product, etc.\n\n   \\*\\* E.g., kombucha, fermented pickled vegetables, etc.\n7. Stable health by medical history, vital signs, physical examination, concomitant medication review, not requiring a change in therapy or medical care for worsening disease within 1 month of enrollment.\n8. Not using medications daily that may affect gut motility, gastric acidity, or baseline gut function\\* within 1 month of enrollment.\n\n   \\*E.g., proton pump inhibitors, opioids, anti-diarrheal agents, anti-constipation agents, daily OTC \"heartburn\" relief medications.\n9. Not using GLP-1 receptor agonists within 6 weeks of enrollment.\n10. Any elective surgery (including dental) that required preoperative or postoperative antibiotics must have been completed at least 1 month prior to enrollment.\n11. Must have had at least 1 of these 3 conditions:\n\n    1. History of CDI (suspected or proven) within the past 3 years, with \"cure\" or no symptoms for at least 1 month prior to enrollment\n    2. History of a hospitalization within the past 3 years, but discharge not sooner than 1 month prior to enrollment\n    3. History of receiving systemic antibiotics known to increase the risk of CDI\\* within the past 3 years, but last dose not sooner than 1 month prior to enrollment \\*Systemic antibiotics that are known to increase risk of CDI include lincosamides (e.g., clindamycin), monobactams (e.g., aztreonam), extended-spectrum penicillin combinations with beta-lactamase inhibitors (e.g., piperacillin-tazobactam), carbapenems (e.g., imipenem, meropenem, ertapenem), third generation or higher cephalosporins, and fluoroquinolones. Common oral antibiotics that would be allowable or are not known to significantly increase the risk of CDI include amoxicillin, azithromycin, cephalexin, doxycycline, metronidazole, and trimethoprim\u002Fsulfamethoxazole.\n12. No history of other enteric infections or diarrheal illness within 1 month of enrollment.\n\nExclusion Criteria:\n\n1. Dwells in a long-term care or skilled nursing facility (living independently with limited nursing care is allowable).\n2. Known to be pregnant or has a positive pregnancy test at screening or enrollment.\n3. Currently breastfeeding a child.\n4. Known to have significant hypersensitivity to any components of the study product; including S. boulardii (or any S. boulardii-based nutritional supplement), hydroxypropyl methylcellulose, and Microcrystalline cellulose \\[MCC\\].\n\n   Hydroxypropyl methylcellulose is the major component of the capsule shell and MCC is the placebo component.\n5. Known to have significant hypersensitivity to a first-line antifungal therapy (i.e., fluconazole or amphotericin B) against Saccharomyces.\n6. Known to be immunocompromised or have known or suspected congenital or acquired immunodeficiency, as determined by the investigator.\n7. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 3 years of enrollment.\n8. Receipt of chronic (\\>\u002F=14 days) immunosuppressive corticosteroids at a dose of \\>\u002F=20 mg prednisone daily or prednisone equivalent within 30 days of enrollment, including oral, parenteral, or high-dose inhaled\\* corticosteroids.\n\n   \\*High-dose inhaled corticosteroid is defined as \\>800 mcg\u002Fday of beclomethasone dipropionate CFC or equivalent. Intra-articular, intranasal, and topical steroids are allowable.\n9. Active malignancy or history of malignancy in the past 3 years (non-melanoma, excised, cured skin cancers are allowed).\n10. History of or testing positive for human immunodeficiency virus (HIV), hepatitis B, or active hepatitis C at screening (positive hepatitis C antibody and detectable hepatitis C virus RNA).\n11. Anticipated or current receipt of kidney dialysis treatment.\n12. Concurrent, acutely life-threatening disease or condition, or any unstable medical history, as determined by the investigator.\n13. Significant chronic gastrointestinal \\[GI\\] condition(s) or disease\\*.\n\n    \\*Includes diagnosis of inflammatory bowel disease or active Rome IV irritable bowel syndrome, poorly controlled Celiac disease, active gastroparesis, toxic megacolon, colostomy, intestinal resection (except uncomplicated appendectomy), ileus, short gut syndrome, or recent (within 6 months of enrollment) diverticular bleeding requiring surgical intervention or transfusion.\n14. Recent (within 6 months of enrollment) history of difficulty with swallowing food, liquids, or pills.\n15. Prosthetic heart valve or indwelling foreign structure within vascular supply (e.g., no central line or indwelling catheter) or known to have moderate to severe valvular disease.\n16. History of alcohol abuse or drug addiction within 5 years of enrollment or that might interfere with the ability to comply with trial procedures.\n17. Diagnosis of schizophrenia, bipolar disease, or other significant psychiatric disease in the opinion of the investigator that may interfere with or pose a problem with compliance with the study or the welfare of the participant.\n18. Presence of mild, acute, or self-limited condition, such as fever or cough or other symptoms of upper respiratory tract infection within 7 days prior to planned randomization.\n19. Any chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion or participant safety.\n20. Identified as a study site or contract research organization employee or family member who is involved in the protocol and may have direct access to trial-related data.\n21. Participating in another clinical trial investigating a vaccine, drug, medical device, or medical procedure within 4 weeks of enrollment through the last visit of the study.",{"count":157,"type":22},86,[25],"This is a Phase 1, first-in-human, double-blind, placebo-controlled, adaptive-design, single-site study, involving dose exploration cohorts.\n\nDuring Part A, up to 4 cohorts, each consisting of approximately 14 healthy adult study participants, will be randomly allocated to receive either FZ002 or placebo. Part A is designed to begin with Cohort 1 evaluating the highest proposed dose of study product. This is intended to represent the \"ceiling\" (highest level) of the ranges of doses to be evaluated in the study. In the event of a safety or tolerability concern in Cohort 1, a dose de-escalation will be evaluated in Cohorts 2-4 until a safe and well-tolerated dose is identified. If no safety or tolerability concerns are identified at the completion of a cohort, the study will proceed to Part B with the approval of the independent Safety Monitoring Committee (SMC). This adaptive design allows for the progression of the study from Part A to Part B without necessarily progressing through all 4 cohorts in Part A if there is a lack of safety or tolerability concerns.\n\nDuring Part B, an initial 'sentinel' Cohort 5 \"some-risk\" adult study participants will be randomly allocated to receive a single daily dose of FZ002 or placebo for 28 consecutive days. This is intended to represent the \"floor\" (lowest level) of doses to be evaluated in the study. A Protocol Safety Review Team (PSRT) will review the available safety data from the first 7 days of Cohort 5. If there is a lack of safety or tolerability concerns over the first 7-days of dosing for Cohort 5, then Cohort 6 will be opened for enrollment. Cohort 6 \"some-risk\" adult study participants will evaluate the \"floor\" and \"ceiling\" dose of FZ002 versus placebo.\n\nThe primary objective is to evaluate safety and clinical tolerability of oral doses of FZ002 or placebo when taken for up to 28 days.",[161],"Clostridium Difficile Infection",[163,164,78,165,166],"Clostridioides difficile","Clostridium difficile","Probiotic Yeast","Tetra-specific Anti-toxin",{"date":40,"type":41},{"date":169,"type":22},"2026-07-27",{"date":171,"type":22},"2028-09-22",{"name":47,"class":48},{"id":174,"slug":175,"hasResults":12,"nctId":176,"briefTitle":177,"officialTitle":178,"acronym":4,"eligibilityCriteria":179,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":126,"enrollmentInfo":180,"targetDuration":4,"studyType":23,"phases":181,"briefSummary":182,"conditions":183,"keywords":185,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":191,"startDateStruct":192,"completionDateStruct":194,"leadSponsor":196,"locationsCount":197},"100634178","phase-1-a-safety-and-immunogenicity-trial-of-ocu500-chad36-vector-encoding-sars-cov-2-spike-vaccine-via-intranasal-and-inhalational-routes-in-previously-vaccinated-adults-100634178","NCT07536308","A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults","A Phase 1 Open-Label Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike, A Next-Generation SARS-CoV-2 Booster Vaccine Via Intranasal and Inhalational Routes, in Previously Vaccinated Adults","Inclusion Criteria:\n\n1. Provides written informed consent before initiation of any study procedures.\n2. Able to understand and agree to comply with planned study procedures and be available for all study visits.\n3. Non-pregnant adults, 18 through 64 years of age at the time of study product administration.\n4. Participants of childbearing potential\\* must agree to use or have practiced true abstinence\\*\\* or use at least one acceptable primary form of contraception.\\*\\*\\*\n\n   \\*These criteria apply to females who are in a heterosexual relationship and are of childbearing potential. Not of childbearing potential include post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, or tubal ligation\u002Fsalpingectomy).\n\n   \\*\\*True abstinence is 100 percent of the time, no sexual intercourse (penis enters the vagina). Periodic abstinence \\[e.g., calendar, ovulation, symptothermal, post-ovulation methods\\] and withdrawal are not acceptable methods.\n\n   \\*\\*\\*Acceptable forms of primary contraception include a monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more before the participant's study product administration, a copper intrauterine device, a levonorgestrel-releasing intrauterine device, a progestin-only oral contraceptive pill, a depot medroxyprogesterone injection, or a progestin implant. Combined hormonal contraceptives containing estrogen, including combined oral contraceptive pills, transdermal patches, and vaginal rings, are not acceptable for this trial. Must have used at least one acceptable primary form of contraception for at least 30 days before study product administration and agree to continue at least one acceptable primary form of contraception through 60 days after study product administration.\n5. Participants of childbearing potential must have a negative urine pregnancy test at screening and within 24 hours before study product administration.\n6. In general, good health.\\*\n\n   \\*As determined by medical history and physical examination, including vital signs, to evaluate acute or ongoing chronic medical diagnoses\u002Fconditions that have been present for at least 90 days, which would affect the assessment of participant safety. Chronic medical diagnoses\u002F conditions should be stable for the last 30 days (i.e., no hospitalization, ER, or urgent care for the condition). This includes no change in chronic prescription medication, dose, or frequency due to deterioration of the chronic medical diagnosis or condition within the 30 days preceding the study product administration. Any prescription change that is due to a change of health care provider, insurance company, etc., or done for financial reasons, and in the same class of medication, will not be considered a deviation of this inclusion criterion. Participants may be on chronic or as-needed (prn) medications if, in the opinion of the participating site PI or appropriate sub-investigator, they pose no additional risk to participant safety or assessment of reactogenicity and immunogenicity.\n7. Receipt of a complete primary COVID-19 vaccine series and at least one booster\\* with last vaccination at least 16 weeks before study product administration.\n\n   \\*Booster may be either homologous or heterologous to the primary vaccine series. It must be an FDA-authorized\u002Flicensed vaccine, though doses may have been received as part of a clinical trial.\n8. Clinical screening laboratory evaluations are within normal reference ranges or grade 1 with no clinical significance (NCS) per investigator discretion.\\*\n\n   \\*(White Blood Cells \\[WBCs\\] with differential \\[diff\\], hemoglobin \\[Hgb\\], platelets \\[PLTs\\], PTT, PT, Alanine Transaminase \\[ALT\\], Aspartate Transaminase \\[AST\\], Creatinine \\[Cr\\], Alkaline Phosphatase \\[ALP\\], Total Bilirubin \\[T. Bili\\]). ALT, AST, ALP, T. Bili, and creatinine values that are below the reference range will not be exclusionary, as these values below the reference range are clinically insignificant.\n9. Must agree to have samples stored for secondary research.\n10. Must complete a Test of Understanding (ToU) before enrollment by answering 90 percent of questions correctly at least once in 3 attempts.\n\nExclusion Criteria:\n\n1. Positive SARS-CoV-2 PCR at screening.\n2. Abnormal vital signs (Grade 1 or higher).\\*\n\n   \\*Grade 1 or higher is equivalent to: Systolic blood pressure (SBP) = 141 mmHg or = 89 mmHg Diastolic blood pressure (DBP) = 91 mmHg Heart rate (HR) is = 101 beats per minute or = 54 beats per minute Oral temperature = 38.0 degrees Celsius (100.4 degrees Fahrenheit)\n3. History of SARS-CoV-2 infection within the prior 16 weeks OR receipt of any COVID-19 vaccine within the prior 16 weeks before study product administration.\n4. Participant who is pregnant or breastfeeding or less than 12 weeks post partum at the time of study product administration.\n5. Participant has donated blood or plasma within 4 weeks prior to study product administration, or does not agree to refrain from blood or plasma donation until Day 181.\n6. Receipt of antibody or blood-derived products within 90 days before study product administration.\n7. Any significant medical or psychiatric diseases or any other condition that, in the opinion of the site PI or appropriate sub-investigator, precludes study participation.\\*\n\n   \\*Significant self-reported or medically reported medical or psychiatric conditions include, but are not limited to drug or alcohol abuse within 6 months of enrollment, significant kidney disease, liver disease, history of hematologic malignancies, ongoing malignancy or recent diagnosis of malignancy in the last five years, excluding treated basal cell and squamous cell carcinoma of the skin, and cervical carcinoma in situ, which are allowed.\n8. Any respiratory disease, including but not limited to chronic obstructive pulmonary disease (COPD), asthma, interstitial lung disease, bronchiectasis, etc.\n9. Neurological or neurodevelopmental conditions.\\*\n\n   \\*These conditions include: history of Bell's palsy, history of four or more migraine headaches in the past 12 months that interfered with normal daily activity or any migraine headache in the past 5 years that required emergency or inpatient medical care, epilepsy, seizures in the last 5 years, encephalopathy, focal neurologic deficits, Guillain-Barré syndrome, myelopathy, peripheral neuropathy, encephalomyelitis, transverse myelitis, stroke or transient ischemic attack, multiple sclerosis, Parkinson's disease, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, or Alzheimer's disease.\n10. Cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease), including any history of myocarditis or pericarditis, or uncontrolled cardiac arrhythmia.\n11. Any autoimmune disease, including hypothyroidism without a defined non-autoimmune cause.\n12. Any significant nasal or upper airway disease.\\*\n\n    \\*Including, but not limited to, being prone to epistaxis, a history of inflammatory rhinitis (including allergic rhinitis) that requires daily medications, cochlear implants, head\u002Fneck radiation history, anosmia\u002Fdysosmia, conditions that require prescription or over the counter intranasal medication (intermittent use will be allowed if no use occurred for 30 days before study product administration and participant agrees to not use intranasal medication (other than steroids) for 30 days after study product administration and to not use intranasal steroids for 6 months after study product administration), and certain ear, nose and throat (ENT) conditions, including significant upper airway\u002Fnasopharyngeal disease or abnormal anatomy such as CSF leak.\n13. Has an acute illness, as determined by the site Principal Investigator or appropriate sub-investigator within 72 hours before study product administration.\\*\n\n    \\*An acute illness which is nearly resolved with only minor residual symptoms remaining is allowable if, in the opinion of the participating site PI or appropriate sub-investigator, the residual symptoms will not interfere with the ability to assess safety parameters as required by the protocol.\n14. Has a positive test result for hepatitis B surface antigen, hepatitis C virus RNA (by reflex testing), or human immunodeficiency virus (HIV) antigen\u002Fantibody test at screening.\n15. Has any confirmed or suspected immunosuppressive or immunodeficient state, such as asplenia, recurrent severe infections, and chronic\\* immunosuppressant medication within the past 6 months.\\*\\*\n\n    \\*Chronic meaning more than 14 continuous days.\n\n    \\*\\*Ophthalmic and topical steroids are allowed, see exclusions 12 and 21 for intranasal steroids.\n16. Has received any investigational product within 60 days, or 5 half-lives, whichever is longer, before study product administration; or is planning to receive one during the study.\n17. Has a history of hypersensitivity or severe allergic reaction\\* to any previous licensed or unlicensed vaccine or to the candidate vaccine components.\n\n    \\*e.g., anaphylaxis, generalized urticaria, angioedema, other significant reaction\n18. History of chronic idiopathic urticaria.\n19. Received or plans to receive licensed inactivated\u002Fsubunit vaccine within 14 days of study product administration or live vaccine within 28 days of study product administration.\n20. Plan to receive a COVID-19 vaccine within the 180 days following study product administration.\n21. Regular use of intranasal medications, including steroids.\\*\n\n    \\*Participant must have had no intranasal medication use for 30 days before study product administration and plans not to use intranasal medications for 30 days after study product administration for medications other than steroids, and for 6 months after study product administration for intranasal steroids (including over-the-counter fluticasone).\n22. History of smoking within three months before enrollment.\\*\n\n    \\*Including cigarettes, smokeless and other tobacco products, e-cigarettes (to include vaping and Juuling products), marijuana, nicotine gum, and nicotine lozenges.\n23. Use of intranasal illicit drugs in the 5 years before study product administration or plans to use during the study.\n24. Planned international travel between study product administration and Day 29.\n25. Previous receipt of any adenovirus-vector vaccine by the intranasal or aerosol routes.\n26. Bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following Intramuscular injections or venipuncture.\n27. Recent (within 3 months of study product administration): major surgery, \\>=3 days immobility, chronic infection, or head trauma that may increase thrombosis risk.\\*\n\n    \\*Major surgery is either abdominal or vascular, or orthopedic surgery, and immobility implies bed rest.\n28. History of venous or arterial thrombosis or any known thrombophilic condition, including heparin-induced thrombocytopenia (HIT) or thrombosis.\n29. BMI \\>\u002F= 40kg\u002Fm\\^2\n30. Current\u002Fplanned systemic estrogen therapy, except stable transdermal estradiol, from 30 days pre-dose through end of study participation. Low-dose vaginal estrogen is permitted.",{"count":128,"type":22},[25],"This phase 1 randomized, open-label, dose-escalation clinical trial evaluates the safety and immunogenicity of OCU500, a ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine, in healthy adults aged 18-64 who previously completed a primary COVID-19 vaccination series and at least one booster. The study evaluates two dose levels (1×10\\^10 viral particles (VP) and 5×10\\^10 VP) and two routes of administration (intranasal and inhaled). The trial includes 80 participants across four study arms (20 per arm). The primary objective is to evaluate the safety and reactogenicity of a single dose of OCU500 administered in previously vaccinated healthy adults.",[184],"COVID-19",[186,137,139,187,188,189,190],"coronavirus","OCU500","Open-label","Phase I","vaccine",{"date":40,"type":41},{"date":193,"type":41},"2026-05-26",{"date":195,"type":22},"2027-11-01",{"name":47,"class":48},6,{"id":199,"slug":200,"hasResults":12,"nctId":201,"briefTitle":202,"officialTitle":203,"acronym":4,"eligibilityCriteria":204,"healthyVolunteers":12,"sex":17,"minAge":205,"maxAge":206,"enrollmentInfo":207,"targetDuration":4,"studyType":23,"phases":209,"briefSummary":210,"conditions":211,"keywords":217,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":222,"startDateStruct":223,"completionDateStruct":224,"leadSponsor":226,"locationsCount":49},"100613161","evaluating-the-safety-and-tolerability-of-baricitinib-in-patients-with-job-syndrome-with-lupus-like-disease-andor-atopic-dermatitis-100613161","NCT07262983","Evaluating the Safety and Tolerability of Baricitinib in Patients With Job Syndrome With Lupus-Like Disease and\u002For Atopic Dermatitis","A Pilot Study to Evaluate the Safety and Tolerability of Baricitinib in Patients With Job s Syndrome With Lupus-like Disease and\u002For Atopic Dermatitis","* INCLUSION CRITERIA:\n\nTo be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. Must be able to understand and provide informed consent or assent.\n2. Aged \\>=12 years.\n3. Documented STAT3 variant causing hyper-IgE syndrome.\n4. Enrollment in NIH protocol 00-I-0159, Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES).\n\n   a. Presence of SLE and\u002For AD as follows: SLE patients should meet either Systemic Lupus International Collaborating Clinics (SLICC) or 2019 American College of Rheumatology (ACR)\u002FEuropean League Against Rheumatism (EULAR) SLE classification criteria. AD is defined as EASI tool score \\>=16 and body surface area tool score of 10% at screening.\n5. Ability to take oral medication and be willing to adhere to the study intervention regimen.\n6. For individuals on glucocorticoids, the dose must be less than 10 mg daily and stable for the 30 days prior to Day 0.\n7. For individuals on hydroxychloroquine or other antimalarials such as chloroquine or quinacrine, the dose must have been stable for 90 days prior to Day 0. The maximum allowed dose is hydroxychloroquine 400 mg\u002Fday or 6.5 mg\u002Fkg\u002Fday, whichever is greater. The maximum allowed dose for chloroquine phosphate is 500 mg daily, and for quinacrine is 100 mg daily.\n8. Individuals may be on lipid-lowering medications if initiated at least 90 days prior to Day 0, and the dose must be stable for 30 days prior to Day 0.\n9. Individuals of reproductive potential must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy while on study drug. Acceptable methods of contraception include:\n\n   * Intrauterine device (IUD)\n   * Bilateral tubal ligation\n   * Abstinence\n   * Vasectomized partner\n   * Hormonal contraception used in combination with barrier method: progestogen containing (oral, intravaginal, transdermal) or progestogen-only (oral, injectable, implantable) starting 30 days prior to initiation of baricitinib\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Known history of hypersensitivity to baricitinib or other JAK inhibitors.\n2. Current or recent use of any investigational drug\u002Fintervention (within 6 months or 5 half-lives, whichever is longer, prior to Day 0) except for COVID-19 vaccines or therapies that have been granted an FDA emergency authorization.\n3. Scheduled to participate in another clinical study involving an investigational drug during the course of this study.\n4. Use of systemic immunosuppressive or immune-modulating agents within 90 days prior to Day 0, except systemic steroids \\\u003C=10 mg of prednisone equivalent per day.\n5. Current or prior treatment with rituximab in the 6 months prior to Day 0.\n6. Current treatment with methotrexate, mycophenolate mofetil, other less common immunomodulatory drugs such as those falling into the class of disease-modifying antirheumatic drugs (DMARDs), belimumab, and other immunosuppressive biologics not otherwise specified herein. Participants previously on methotrexate, mycophenolate mofetil, azathioprine, tacrolimus, cyclosporine, or belimumab, other immunosuppressive biologics, or DMARDs should have been withdrawn from the drug for at least 90 days prior to Day 0.\n7. Treatment with cyclophosphamide and pulse methylprednisolone within 6 months prior to Day 0.\n8. Hypercholesterolemia: Values after 8- to 12-hour fasting blood specimen: total cholesterol \\>250 mg\u002FdL or LDL \\>180 mg\u002FdL or hypertriglyceridemia (triglyceride \\>300 mg\u002FdL) within 90 days prior to Day 0.\n9. History of alcohol or drug abuse within 6 months prior to Day 0.\n10. Presence of 1 or more of the following clinically significant laboratory abnormalities:\n\n    1. Serum ALT \\>=3 times ULN.\n    2. Serum total bilirubin \\>=2 times ULN.\n    3. ANC \\\u003C=750 cells\u002FmicroL.\n    4. Hemoglobin \\\u003C=9.0 g\u002FdL.\n    5. Platelet count \\\u003C=100,000\u002FmicroL.\n    6. Serum creatinine \\>=2 times ULN.\n11. Planned or anticipated major surgical procedure during the study.\n12. Plans to receive any live vaccines within 1 month of the anticipated first dose of baricitinib.\n13. Known or suspected immune-dysregulatory disorders besides Job s syndrome, lupus-like disease, and\u002For AD.\n14. Active invasive opportunistic infections (eg, non-TB mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis pneumonia, aspergillosis) despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged infections suggesting an immune-compromised status as judged by the investigator.\n15. Known active TB. Participants with treated LTB will be eligible to participate. Participants with untreated LTB will not be excluded but will be evaluated by an infectious disease consultant and may become eligible for trial based on infectious disease consultant recommendations.\n16. Infection with HIV.\n17. Untreated infection with hepatitis B or C.\n18. Unwillingness to receive prophylactic entecavir (or similar), only for individuals with evidence of clearance of hepatitis B with positive hepatitis B core and surface antibody and negative hepatitis B surface antigen and PCR.\n19. BK or JC viremia at screening visit.\n20. Active infection that requires the use of oral or intravenous antimicrobials that remains unresolved at least 14 days prior to the administration of the first dose of study medication.\n21. Individuals with active renal or central nervous system disease or a high activity level in any organ system (except articular) that requires immediate immunosuppressive therapy as determined by the investigator.\n22. History of cancer, with the exceptions of basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix, provided the participant is in remission and curative therapy was completed at least 12 months prior to screening. History of other malignancies are also permitted provided that the individual is in remission and curative therapy was completed at least 5 years prior to screening.\n23. Planned or anticipated use of any prohibited medications and procedures during the study.\n24. Pregnancy or current breastfeeding.\n25. Currently receiving hemodialysis or peritoneal dialysis.\n26. Past or current medical problems or findings from physical examination, electrocardiogram, or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risk from participation in the study, may interfere with the individual s ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. These may include, but are not limited to:\n\n    1. Known coronary artery aneurysm.\n    2. Known history of arterial or venous thrombosis or at high risk for clotting disorder.\n    3. Known history of PE or DVT in the past.\n    4. Psychiatric illness or history of medical non-compliance that the study team feels will make the individual unlikely to complete the study.\n    5. Significant impairment of major organ function (lung, heart, liver, kidney) or any condition that, in the opinion of the investigator, would jeopardize the individual s safety following exposure to the study drug.\n27. Individuals with known increased risk factors for MACE including a history of:\n\n    1. Ischemic heart disease (eg, history of acute myocardial infarction).\n    2. Heart failure.\n    3. Cardiomyopathy.\n    4. Severe valvular heart disease.\n    5. Significant arrhythmias.\n    6. Chronic renal failure.\n    7. Cerebrovascular accident or transient ischemic attack.\n    8. Uncontrolled diabetes mellitus.\n    9. Uncontrolled hypertension.\n    10. Current smokers or former smokers with less than 3 years since complete cessation and\u002For \\>20 pack-years of smoking history.\n28. History of idiopathic GI perforation or diverticulitis with high risk of perforation.\n29. Treatment with strong organic anion transporter 3 inhibitors (OAT3) (eg, probenecid) due to drug interactions.\n30. Uncontrolled thyroid disease as per principal investigator or medically responsible investigator.","12 Years","120 Years",{"count":208,"type":22},20,[25],"Background:\n\nAutosomal dominant hyper-IgE syndrome (HIES), also called Job syndrome, is a genetic disorder that affects the immune system. It can cause skin and lung infections and problems with blood vessels, connective tissues, and bones. People with HIES often have lupus-like disease or atopic dermatitis (skin rash). Researchers want to know if a drug approved to treat other immune system diseases (baricitinib) can help people with HIES.\n\nObjective:\n\nTo test baricitinib in people with HIES with lupus-like disease or skin rash.\n\nEligibility:\n\nPeople aged 12 years and older with HIES with lupus-like disease or skin rash.\n\nDesign:\n\nParticipants will have 5 clinic visits, 4 remote visits, and 2 phone visits in 9 months.\n\nParticipants will be screened. They will have a physical exam with blood and urine tests. They will have tests of the speed and pressure of blood flow through their body: Blood pressure cuffs will be placed on each arm and leg; electrodes will be placed on the wrists and a microphone on the chest.\n\nThe study has a 3-month lead-in period. Participants will not take the study drug during this time. They will continue with their usual medical care. They will have 2 phone calls with the study team.\n\nBaricitinib is a tablet taken by mouth. Participants will take 1 or 2 tablets by mouth every day for 6 months. They will start with a low dose and may increase to a higher dose.\n\nBlood and urine tests will be repeated during each study visit. Other tests may also be repeated during some visits. A skin sample may also be taken....",[212,213,214,215,216],"Hyper IgE Syndrome From STAT3 Mutation","Job s Syndrome","HIES","Lupus","Atopic Dermatitis",[212,218,214,215,216,219,220,221],"Job s syndrome","Lupus-like Disease","JAK Inhibition","Janus Kinases",{"date":40,"type":41},{"date":43,"type":22},{"date":225,"type":22},"2030-10-01",{"name":47,"class":48},{"id":228,"slug":229,"hasResults":12,"nctId":230,"briefTitle":231,"officialTitle":232,"acronym":4,"eligibilityCriteria":233,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":234,"enrollmentInfo":235,"targetDuration":4,"studyType":23,"phases":237,"briefSummary":238,"conditions":239,"keywords":241,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":243,"startDateStruct":244,"completionDateStruct":245,"leadSponsor":247,"locationsCount":248},"100609536","bpl-1357-against-h1n1-influenza-virus-challenge-100609536","NCT07215858","BPL-1357 Against H1N1 Influenza Virus Challenge","Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study of the Safety and Efficacy of BPL-1357 Against H1N1 Influenza Virus Challenge","* INCLUSION CRITERIA:\n\nIndividuals must meet all of the following criteria to be eligible for study participation:\n\n1. Adults \\>=18 and \\\u003C= 55 years of age at the time of consent.\n2. Able to provide written informed consent.\n3. Non-smoker (i.e., tobacco and cannabis) and does not use vape or e-cigarette products currently. Also, must not have used any of these products extensively in the past (regular use more than 5 times per week, more than 6 months lifetime total).\n4. Has not received influenza vaccination of any type within 6 months prior to enrollment and consents to not receive influenza vaccination of any type until after the end of study participation (PBD63).\n5. Has not received any other vaccination of any type within 4 weeks prior to enrollment and consents to not receive any unlicensed vaccine until after the end of the study (PBD63).\n6. Has not received any broadly protective influenza vaccine in the past.\n7. Participants of childbearing potential must meet one of the following criteria through the end of study participation (PBD63):\n\n   1. Is infertile, including postmenopausal status (as defined by age \\>=45 years plus no menses for \\>= 1 year without an alternative medical cause) or history of hysterectomy or bilateral oophorectomy.\n   2. Agrees that, when engaging in intercourse that can result in pregnancy, they will use an acceptable or highly effective form of contraception, and their male partner will use a condom with spermicide. Acceptable methods of female contraception include\n\n   the following:\n   * Bilateral tubal ligation\n   * Implant of levonorgestrel\n   * Injectable progestogen\n   * Oral contraceptive pills\n   * Diaphragm with spermicide\n   * Intrauterine device (IUD)\n   * Sexual abstinence\n   * Vasectomized partner\n8. Able to speak and understand English.\n9. A negative HIV test within 6 months before enrollment.\n10. Has not used IN medications (including but not limited to nasal sprays, sinus rinses), and has not routinely used over-the-counter medications (including but not limited to aspirin, decongestants, antihistamines, and other nonsteroidal anti-inflammatory drugs), and herbal medications (including but not limited to herbal tea or St. John's Wort) within 14 days (about 2 weeks) prior to study enrollment and agrees not to use these medications until after the end of study participation (PBD63), unless approved by the investigator.\n11. Agrees not to donate blood or blood products from enrollment through the final study visit (PBD63).\n12. Not planning on cohabitating with any high-risk individuals (e.g., infants, elderly, those with high-risk conditions (e.g., pregnancy, medical conditions such as those outlined in exclusion criterion 1) for at least 2 weeks after discharge from the inpatient portion of this study.\n13. Participant is willing and able to comply with all trial procedures.\n\nEXCLUSION CRITERIA\n\nIndividuals meeting any of the following criteria will be excluded from study participation:\n\n1. Current medical conditions (self-reported or medically documented) including but not limited to:\n\n   1. Chronic pulmonary disease (e.g., asthma, emphysema).\n   2. Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).\n   3. Chronic medical conditions requiring close medical follow-up or hospitalization (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).\n   4. Immunosuppression, immune deficiency, or ongoing malignancy.\n   5. Neurological and neurodevelopmental condition (e.g., Bell s palsy, cerebral palsy, epilepsy, seizures).\n2. Body mass index (BMI) \\\u003C18 and \\>35.\n3. Pregnant or breastfeeding.\n4. History of postinfectious or postvaccine neurological sequelae including GBS.\n5. History of stroke within the past 5 years.\n6. Acute illness within 7 days prior to enrollment (PAD0).\n7. Known allergy to influenza vaccination or components contained in the influenza vaccine being used.\n8. Known allergy to influenza treatments (including oseltamivir or nonsteroidal anti-inflammatory medications).\n9. Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides).\n10. Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.\n11. Receipt of any unlicensed drug or investigational agent within 3 months or 5.5 half-life (whichever is greater) prior to enrollment.\n12. Receipt of any unlicensed vaccine within 6 months prior to enrollment.\n13. Self-reported or known history of alcoholism or drug abuse or use within 6 months prior to enrollment, or positive urine test for illicit drugs (i.e., amphetamines, cocaine metabolites, benzodiazepines, opiates, but not tetrahydrocannabinol) prior to vaccination on PAD0.\n14. Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the PI to be a contraindication to protocol participation.\n15. History of angioedema or anaphylaxis.\n16. Study site staff who directly report to the study or site PI are excluded from participation.\n17. Any condition, event or lab value that, in the judgment of the investigator, is a contraindication to protocol participation or would place the participant at increased risk for participation.\n18. Any condition or event that, in the judgment of the investigator, impairs the participant's ability to give informed consent.\n\nIndividuals meeting any of the following criteria will be excluded from participation in Phase B:\n\n1. Positive urine test for illicit drugs (i.e., amphetamines, cocaine metabolites, benzodiazepines, opiates, but not tetrahydrocannabinol) prior to inoculation (PBD0).\n2. Acute illness within 7 days prior to inoculation with the human challenge virus (PBD0).\n3. Grade 3 or greater sign, symptom, or lab abnormality that is clinically significant and (in the opinion of the site PI) puts the participant at higher risk of adverse effects with influenza challenge.\n4. Pregnant or breastfeeding.\n5. Positive test for influenza within 8 weeks prior to challenge.","55 Years",{"count":236,"type":22},129,[26],"Background:\n\nInfluenza (flu) infections are a serious global health threat. Each year, between 3 and 5 million people get the flu, and up to 500,000 die from it. Current vaccines protect against seasonal flus, but broader vaccines are needed to protect against potential flu pandemics.\n\nObjective:\n\nTo test an experimental flu vaccine.\n\nEligibility:\n\nHealthy people aged 18 to 55 years.\n\nDesign:\n\nThe study will last 5 to 8 months and has 2 phases, A and B.\n\nThe study vaccine will be given either as a shot in the arm or as a nasal spray. Participants will receive 1 of 3 combinations: (1) study vaccine in the nose and placebo in the arm; (2) placebo in the nose and study vaccine in the arm; or (3) placebo in the nose and placebo in the arm. A placebo is just like the real vaccine but contains no active ingredients.\n\nPhase A: Participants will have 5 clinic visits over 56 days. They will receive a shot and a nasal spray at 2 of the visits, 28 days apart. At each visit, they will have a physical exam, with tests of their blood, urine, and nasal secretions. They will check their temperature at home and record any symptoms for 7 days after each vaccine.\n\nPhase B: Participants will stay in the hospital for at least 9 days. They will be infected with a flu virus. They will provide blood, urine, and nasal fluid samples. They will have tests of their heart function. They will remain in the hospital until they test negative for the flu 2 days in a row.\n\nThey will have 2 follow-up visits, 4 and 8 weeks after leaving the hospital.\n\n...",[65,240],"Human",[65,82,242],"Human Challenge",{"date":40,"type":41},{"date":43,"type":22},{"date":246,"type":22},"2028-03-01",{"name":47,"class":48},2,{"id":250,"slug":251,"hasResults":12,"nctId":252,"briefTitle":253,"officialTitle":254,"acronym":4,"eligibilityCriteria":255,"healthyVolunteers":12,"sex":17,"minAge":58,"maxAge":256,"enrollmentInfo":257,"targetDuration":4,"studyType":23,"phases":259,"briefSummary":261,"conditions":262,"keywords":265,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":267,"startDateStruct":268,"completionDateStruct":269,"leadSponsor":271,"locationsCount":272},"100595082","the-esophageal-string-test-as-a-diagnostic-screening-tool-for-eosinophilic-esophagitis-among-africans-with-dysphagia-in-mali-and-the-united-states-100595082","NCT07027826","The Esophageal String Test as a Diagnostic Screening Tool for Eosinophilic Esophagitis Among Africans With Dysphagia in Mali and the United States","Use of the Esophageal String Test as a Diagnostic Screening Tool for Eosinophilic Esophagitis Among Africans With Dysphagia in Mali and the United States","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n1. Able to provide informed consent.\n2. Aged 18 to 65 years.\n3. Born in the African continent or their parents were born in Africa,\n4. Exhibiting symptoms of dysphagia and\u002For prior history of food impaction.\n5. Undergoing clinically indicated endoscopy at the NIH Clinical Center (U.S.), Centre Hospitalier Universitaire Gabriel Tour(SqrRoot)(Copyright) (Mali), or other local clinics (Mali) and willing to provide research samples and data.\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Recent steroid use (systemic or swallowed\u002Ftopical corticosteroid) within 4 weeks prior to endoscopy.\n2. Recent use of dupilumab (Dupixent) within the last 6 months.\n3. Recent use of other biologic medications (within either 6 months or 5 half-lives, whichever is longer). Examples of biologic medications include:\n\n3a. mepolizumab (Nucala)\n\n3b. reslizumab (Cinqair, Cinqaero)\n\n3c. benralizumab (Fasenra)\n\n3d. cendakimab\n\n3e. tezepelumab (Tezspire)\n\n3f. barzolvolimab\n\n4\\. Individuals suffering from a bleeding diathesis (e.g., hemophilia, severe thrombocytopenia).\n\n5\\. Current use of anticoagulant medications.\n\n6\\. Pregnancy.\n\n7\\. Treatment with another investigational drug or other investigational intervention within 6 months or 5 half-lives whichever is longer.\n\n8\\. Individuals with a known history of any of the following:\n\n8a. eosinophilic esophagitis\n\n8b. esophageal stricture unable to be passed with an upper endoscope\n\n8c. esophageal cancer\n\n8d. esophageal motility disorder (e.g., achalasia)\n\n8e. esophageal varices\n\n8f. esophageal or gastric surgery including fundoplication\n\n8g. neurologic cause of dysphagia (e.g., stroke, Parkinson s disease, etc.)\n\n8h. allergy to gelatin\n\n8i. inability to swallow pills\n\n9\\. Any condition that, in the investigator s opinion, places the individual at undue risk by participating in the study.\n\nCo-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the principal investigator in consultation with the medical monitor. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the principal investigator.","65 Years",{"count":258,"type":22},70,[260],"NA","Background:\n\nEosinophilic esophagitis (EoE) is a disease that causes inflammation in the esophagus. The esophagus is the tube that moves food from the mouth to the stomach. Diagnosing EoE currently requires a specialized tool called an endoscope. The esophageal string test (EST) is another test; the EST collects fluid from the upper digestive tract. An EST is simpler and cheaper than an endoscopy. Researchers want to know if an EST can diagnose EoE.\n\nObjective:\n\nTo test if the EST can diagnose EoE in people who have trouble swallowing.\n\nEligibility:\n\nAdults aged 18 to 65 years with trouble swallowing. They must have been born in the African continent or their parents were born in Africa.\n\nDesign:\n\nParticipants will be screened. They will give blood, stool, urine, and skin swab samples. They will complete surveys about their medical history, diet, symptoms, and home environment. They will bring a sample of their drinking water for testing.\n\nParticipants will have an EST. They will swallow a pill capsule that contains a nylon string. One end of the string will be taped to their cheek. The string will unravel down the esophagus and into the stomach. It will be pulled out after 1 hour. Fluids that soaked into the string will be tested.\n\nAt a different visit, participants will have an endoscopic exam. An endoscope is a flexible tube that is inserted down the mouth; it can be used to take tissue samples from the esophagus, stomach, and small intestine.\n\nParticipants will have a final visit in person, online, or by phone. They will take a survey and talk about their test results.",[263,264],"Dysphagia","Eosinophilic Esophagitis",[264,263,266],"Esophageal string test",{"date":40,"type":41},{"date":43,"type":22},{"date":270,"type":22},"2027-08-31",{"name":47,"class":48},3,{"id":274,"slug":275,"hasResults":12,"nctId":276,"briefTitle":277,"officialTitle":277,"acronym":4,"eligibilityCriteria":278,"healthyVolunteers":12,"sex":17,"minAge":279,"maxAge":206,"enrollmentInfo":280,"targetDuration":4,"studyType":99,"phases":4,"briefSummary":282,"conditions":283,"keywords":285,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":289,"startDateStruct":290,"completionDateStruct":291,"leadSponsor":293,"locationsCount":248},"100552957","modeling-host-pathogen-interaction-using-lymphoid-organoids-100552957","NCT06479837","Modeling Host-Pathogen Interaction Using Lymphoid Organoids","* INCLUSION CRITERIA:\n\nTo be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Aged \\>=2 yrs.\n* Undergoing tonsillectomy as part of their clinical care.\n* Able to provide informed consent (for ages \\>=18 years) or has a parent or guardian who can provide informed consent on their behalf (for ages \\\u003C18 yrs).\n* Willing to allow samples and data to be stored and shared for future secondary research.\n* Willing to allow future genetic testing on their biospecimens.\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Active infection.\n* Active tonsilitis.\n* Pregnant.\n* Diagnosed with an immunosuppressive condition or currently taking immunosuppressive medications.\n* Current or past intravenous drug use.\n* Any condition that, in the judgment of the investigator, may put the participant at undue risk or make them unsuitable for participation in the study","2 Years",{"count":281,"type":22},500,"Background:\n\nStaphylococcus aureus (S.aureus) are bacteria that can make people sick. Sometimes, an S. aureus infection can develop inside the spine; these infections can lead to paralysis and death. Researchers do not know how S. aureus interacts with a person s cells to cause infections in the spine.\n\nObjective:\n\nTo learn how S. aureus interacts with cells in the body using tissues from tonsils discarded after standard surgery to remove them.\n\nEligibility:\n\nPeople aged 2 years and older who are scheduled to have their tonsils removed.\n\nDesign:\n\nResearchers will select participants for the study based on review of their existing medical records, including results of blood tests; any imaging scans, including x-rays; and reports about tissue specimens.\n\nParticipants will answer questionnaires about their health and past infections. They can do this online or on paper.\n\nParticipants will collect a nasal swab 1 week before their surgery. They will be given a tool that looks like a long cotton swab. They will twirl it around inside their nose. The swab will pick up cells and fluids that will be used for research.\n\nAfter their surgery, the participant s surgeon will save samples of tonsil tissue. The surgeon will send these tissue samples and the nasal swab to researchers at the NIH.\n\nThese tissues and the swab will be used in studies to help researchers understand how S. aureus interacts with cells in the body. They hope these studies will help them find better ways to treat S. aureus infections.",[284],"Staphylococcal Infections",[286,287,288],"Organoid","Staphylococcus","Host-pathogen Interactions",{"date":40,"type":41},{"date":43,"type":22},{"date":292,"type":22},"2044-12-01",{"name":47,"class":48},{"id":295,"slug":296,"hasResults":12,"nctId":297,"briefTitle":298,"officialTitle":298,"acronym":4,"eligibilityCriteria":299,"healthyVolunteers":57,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":300,"targetDuration":4,"studyType":99,"phases":4,"briefSummary":302,"conditions":303,"keywords":308,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":313,"startDateStruct":314,"completionDateStruct":316,"leadSponsor":318,"locationsCount":49},"100489688","a-repository-to-study-host-microbiome-interactions-in-health-and-disease-100489688","NCT05656378","A Repository to Study Host-Microbiome Interactions in Health and Disease","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Aged \\>0 years. Only participants \\>3 years old will be seen at the NIH CC.\n* Willing to allow biological samples and data to be stored for future research.\n* Willing to provide at least one of the requested biospecimens.\n\nEXCLUSION CRITERIA:\n\n* An individual who has any condition that, in the judgment of the investigator, may put them at undue risk or make them unsuitable for participation in the study will be excluded.\n* For additional gastrointestinal and skin biopsies only, individuals on blood thinners unless they have already been stopped for the procedure, and children aged younger than 3 years.\n* For additional gastrointestinal biopsies only, individuals who have a history of gastrointestinal perforation with endoscopic biopsies will be excluded from the collection of additional gastrointestinal biopsies for the repository.\n* For additional gastrointestinal biopsies only, healthy children (\\\u003C18 years old).\n* For skin biopsies only, individuals who have a history of keloid formation.\n* For vaginal swabs and vaginal fluid only, individuals who have not started menses.\n* For breast milk only, non-lactating individuals.",{"count":301,"type":22},600,"Background:\n\nThe microbiome is the bacteria and other microorganisms that live inside and on the body. The microbiome is important for our health. Researchers study how the microbiome help people stay healthy. They study how the microbiome affects the body when people get sick. To do this research, they need samples of the microbiome living on the bodies of many people. The purpose of this natural history study is to collect microbiome samples in a repository. These samples will be used for future research.\n\nObjective:\n\nTo collect microbiome samples from the body that can be used for future research.\n\nEligibility:\n\nPeople of any age. Only those older than 3 years will be seen at the NIH clinic.\n\nDesign:\n\nParticipants will fill out a questionnaire. Topics will include their medical history and foods they eat.\n\nParticipants will be asked to give 1 or more of the following:\n\nStool, urine, saliva, vaginal fluid, and breastmilk. These samples can be collected at home and sent to the researchers.\n\nCells from participants cheek, nose, mouth, skin, rectum, and\u002For vagina. The cells may be collected by rubbing the area with a sterile cotton swab. These procedures can also be done at home.\n\nBlood. Blood may be drawn using a needle inserted into a vein in the arm. For young children, blood may be collected by a prick on the heel or finger.\n\nIntestinal tissue samples. These may be collected from participants who are having an endoscopy or colonoscopy for other reasons.\n\nSkin tissue samples. These may be collected from participants who are having biopsies for other reasons.",[304,305,306,307],"Healthy Controls","Pregnancy","Pediatric Illnesses","Inflammatory Diseases",[309,310,311,305,312],"Microbiome","Host Response","Children","Natural History",{"date":40,"type":41},{"date":315,"type":41},"2023-03-09",{"date":317,"type":22},"2032-01-01",{"name":47,"class":48},{"id":320,"slug":321,"hasResults":12,"nctId":322,"briefTitle":323,"officialTitle":324,"acronym":4,"eligibilityCriteria":325,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":234,"enrollmentInfo":326,"targetDuration":4,"studyType":23,"phases":328,"briefSummary":329,"conditions":330,"keywords":335,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":338,"startDateStruct":339,"completionDateStruct":340,"leadSponsor":342,"locationsCount":49},"100489389","early-metabolic-effects-of-antiretroviral-drugs-in-healthy-volunteers-a-phase-2-randomized-study-100489389","NCT05652478","Early Metabolic Effects of Antiretroviral Drugs in Healthy volUnteers: a Phase 2 Randomized Study","Early Metabolic Effects of Antiretroviral Drugs in Healthy Volunteers: A Phase 2 Randomized Study","* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\n* Aged 18 to 55 years.\n* Able to provide informed consent.\n* Willing to allow samples and data to be stored and shared for future research.\n* Agrees to use a barrier method of contraception or abstain from sexual activity starting at screening though the end of study participation.\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Current infection with HIV or hepatitis A, B, or C.\n* Body mass index (BMI) \\\u003C18.5 kg\u002Fm\\^2 or \\>30.0 kg\u002Fm\\^2.\n* Weight change \\>5% in the past 6 months.\n* History of or current cardiovascular disease such as congestive heart failure, heart block, or clinically relevant abnormal ECG as determined by investigators.\n* History of or current liver disease or alanine transaminase serum level \\>2x upper limit of normal.\n* History of or current kidney disease or renal insufficiency, or estimated creatinine clearance \\\u003C=80 mL\u002Fmin (Modification of Diet in Renal Disease equation).\n* Current cancer or history of cancer within 5 years of screening, with the exception of squamous cell carcinoma or basal cell carcinoma that is localized and does not require systemic therapy.\n* History of bariatric surgery.\n* Diabetes mellitus as defined by a prior diagnosis or a hemoglobin A1c of \\>6.4 percent on screening labs.\n* Fasting serum glucose \\>126 mg\u002FdL.\n* History of or current hypo- or hyper-thyroid or abnormal TSH, except minor deviations deemed to be of no clinical significance by the investigator.\n* History of chronic obstructive pulmonary disease.\n* Psychological conditions by self-report, such as (but not limited to) clinical depression, or bipolar disorders, which would be incompatible with safe and successful participation in this study.\n* Pregnancy or within 1 year post-partum.\n* Breastfeeding.\n* Blood pressure \\>140\u002F90 mm Hg or current antihypertensive therapy.\n* Hemoglobin that is either 10 percent below the lower limit or 10 percent above the upper limit of the normal range for the Clinical Center Laboratory (acceptable ranges: females 10.08-17.27 g\u002FdL, males 12.33-19.25 g\u002FdL).\n* History of illicit drug, opioid, or alcohol abuse within the last 5 years; current use of illicit drugs or opioids (by history) or excessive alcohol (CAGE assessment score \\>=2).\n* Current use of the following prescription or over-the-counter medications and supplements:\n\n  * Carbamazepine\n  * Oxcarbazepine\n  * Phenobarbital\n  * Phenytoin\n  * Primidone\n  * Rifabutin\n  * Rifampin\n  * Rifapentine\n  * St. John's wort (Hypericum perforatum)\n  * Cation-containing antacids or laxatives\n  * Sucralfate\n  * Buffered medications\n  * Oral calcium, iron, magnesium, or zinc supplements, including multivitamins containing these polyvalent cations\n  * Dalfampridine\n  * Metformin\n  * Dofetilide\n  * Thyroid medications\n  * Corticosteroids\n  * Weight loss medications, including prescription drugs (eg, semaglutide and tirzepatide) and over-the-counter diet pills\n* Use of TAF, TDF, and\u002For FTC for the purpose of HIV PrEP or in a research study within the past 6 months.\n* Any history of exposure to cabotegravir or lenacapavir (eg, as HIV PrEP or as a participant in a research study for these drugs).\n* Current use of prescription or nonprescriptive medications that may have interactions with study drugs or confound the study measurements as determined by the investigators.\n* History of adverse or allergic reactions to the study drugs.\n* Daily caffeine intake \\>500 mg (about 4 cups of coffee).\n* Current smoker or user of tobacco products.\n* A change in the participant's diet and\u002For exercise regimen in the past 3 months or during the timeframe of the study period that, in the opinion of the investigator, would compromise the integrity of the data.\n* High-risk sexual activity as determined by the investigators, and\u002For inability or unwillingness to use barrier contraception during the protocol.\n* Any other condition, medication, or dietary pattern that, in the opinion of the investigators, increases risk to the participant, prevents the participant from complying with study procedures, prevents the participant from completing the study, or interferes with the interpretation of study results.",{"count":327,"type":22},120,[26],"Background:\n\nPeople with HIV take drugs to keep the amount of virus in their body low. One type of these drugs, called integrase strand transfer inhibitors (INSTIs), can cause weight gain over time. Weight gain can cause diabetes, heart disease, and other serious issues. Researchers want to understand how INSTIs cause weight changes.\n\nObjective:\n\nTo characterize the change in plasma metabolite profile that 4 weeks of each treatment may induce in the absence of HIV infection\n\nEligibility:\n\nHealthy people aged 18 to 55.\n\nDesign:\n\nParticipants will be screened in the outpatient clinic. They will have a physical exam and blood tests. They will have a nutritional assessment and tests of their heart function.\n\nParticipants will be randomized to one of four oral treatments: Tenofovir Disoproxil Fumarate TDF, Tenovovir Alafenamide TAF\u002FVemlidy, Dolutegravir DTG\u002FTivicay, or both TAF and DTG taken together for 4 weeks.\n\nParticipants will have a Day 0 visit for the Lead-In Baseline visit for an exam and blood tests and continuous glucose monitor placement.\n\nParticipants will return in 2wks or Day 14\u002FWk 2 for a DEXA (dual-energy X-ray absorptiometry). DEXA is a kind of X-ray that measures body fat and bone density. Optional adiopse (fat) tissue biopsy in the abdomen, and optional microbiome specimen collections. Continuous glucose monitor changed. Oral once a day dose medication will be started with education.\n\nParticipants will return in 2wks or Day 28\u002FWk 4 for exam, labs, and continuous glucose monitor changed.\n\nParticipants will return in 2wks or Day 42\u002FWk 6 for final exam, labs, repeat DEXA scan, repeat adipose tissue biopsy, and microbiome specimen collections.",[331,332,333,334],"Healthy Volunteer","Weight Gain","Metabolic Effects","Integrase Strand Transfer Inhibitors",[336,337,334],"Metabolism","HIV",{"date":40,"type":41},{"date":43,"type":22},{"date":341,"type":22},"2030-01-31",{"name":47,"class":48},{"id":344,"slug":345,"hasResults":12,"nctId":346,"briefTitle":347,"officialTitle":347,"acronym":4,"eligibilityCriteria":348,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":349,"enrollmentInfo":350,"targetDuration":4,"studyType":99,"phases":4,"briefSummary":352,"conditions":353,"keywords":358,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":38,"lastUpdatePostDateStruct":360,"startDateStruct":361,"completionDateStruct":363,"leadSponsor":365,"locationsCount":49},"100357727","collection-of-human-biospecimens-for-basic-and-clinical-research-into-globin-variants-100357727","NCT03937817","Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants","* PARTICIPANT INCLUSION CRITERIA:\n\n  1. Aged 18-70 years.\n  2. Able to provide informed consent.\n  3. Willing to allow biological samples to be stored for future research.\n  4. Willing to provide one or more of the following tissues: saliva, urine, blood, blood waste products, adipose tissue, bronchial brushing, and\u002For BAL samples.\n  5. Willing to allow genetic testing on collected biological samples.\n\n     PARTICIPANT EXCLUSION CRITERIA:\n* Exclusion Criteria for All Participants\n\nThe following exclusion criteria apply to all participants who will provide any of the following samples in-person at the NIH CC: saliva, urine, blood, blood waste products, adipose tissue, bronchial brushing, and\u002For BAL samples:\n\n1. Pregnancy.\n2. Positive testing for hepatitis B virus, hepatitis C virus, or HIV (as determined by serum screening tests or relevant viral quantitative studies.)\n3. Any condition that requires active medical intervention or monitoring to avert serious danger to the individual s health or wellbeing.\n4. Any condition that, in the opinion of the PI, contraindicates participation in this study.\n\n   * Additional Exclusion Criteria for Individuals Giving Blood for Research\n\n1\\. Hemoglobin \\\u003C 10 g\u002FdL for healthy female volunteers, \\\u003C 12 g\u002FdL for healthy male volunteers, or \\\u003C 6 g\u002FdL for participants with sickle cell disease or other chronic anemias.\n\n-Additional Exclusion Criteria for Adipose Tissue Biopsy\n\nIndividuals meeting any of the following criteria will be excluded from undergoing adipose tissue biopsy. If the participant no longer meets any of these criteria at a later time, then they will be allowed to undergo this procedure.\n\n1. Currently taking anticoagulation medication.\n2. Platelets \\\u003C 100,000\u002FmicroL.\n3. History of keloid formation (or irregular fibrous tissue formed at the site of a scar or injury).\n4. History of adverse reactions to lidocaine or other local anesthetics.\n5. Any condition that, in the opinion of the PI, contraindicates this procedure.\n\nUse of aspirin (or acetylsalicylic acid) and nonsteroidal anti-inflammatory drugs (NSAIDs) are permitted.\n\n-Additional Exclusion Criteria for Bronchoscopy\n\nIndividuals meeting any of the following criteria will be excluded from undergoing bronchoscopy. If the participant no longer meets any of these criteria at a later time, then they will be allowed to undergo this procedure.\n\n1. Prothrombin time (PT) \\> 1 second above the upper limit of normal (ULN) or international normalized ratio \\> 1.3.\n2. Partial thromboplastin time (PTT) \\> 1 second above ULN.\n3. Platelets \\\u003C 150,000\u002FmicroL.\n4. Currently taking anticoagulation medication.\n5. Use of aspirin within 2 weeks of the bronchoscopy or NSAIDs within 2 days of the bronchoscopy.\n6. Diagnosis of a pulmonary disorder (eg, asthma, chronic bronchitis, cystic fibrosis, or bronchiectasis).\n7. Respiratory tract infection within the last 4 weeks.\n8. History of adverse reactions to systemic and\u002For local anesthetics that will be used for this procedure.\n9. History of cigarette smoking within the past 3 months.\n10. History of chronic opioid use.\n11. History of drug or alcohol abuse.\n12. Post-bronchodilator forced expiratory volume in 1 second (FEV1) \\\u003C 40% of predicted or pre-bronchodilator FEV1 \\\u003C 35% of predicted.\n13. Active bronchospasm on physical examination.\n14. History of lidocaine allergy.\n15. Any condition that, in the opinion of the PI, contraindicates this procedure.\n\nCo-enrollment guidelines: Participants may be co-enrolled in other studies. However, the PI must be notified of co-enrollment.","70 Years",{"count":351,"type":22},300,"Background:\n\nBlood disorders like sickle cell disease and malaria affect many people around the world. Researchers want to learn more about blood disorders. To do this, they need to collect biological samples from people with blood disorders. They also need to collect samples from healthy people.\n\nObjective:\n\nTo collect samples to use for research on blood disorders.\n\nEligibility:\n\nPeople ages 18-70 who have blood disorders. Healthy volunteers without blood disorders are also needed.\n\nDesign:\n\nParticipants will be screened with a medical history, physical exam, and blood and urine tests.\n\nParticipants will give one or more samples. They will give them over 5 years. They can choose not to give any of the samples:\n\nSaliva: Participants will spit into a tube. They may also have the inside of their mouth swabbed.\n\nUrine: Participants will urinate into a cup.\n\nBlood and blood waste products: Blood will be taken through a needle in the participant s arm.\n\nFat samples: An area on the participant s belly or buttock will be numbed. A small cut will be made into the skin and a small piece of fat removed.\n\nMucus and cells from the lungs: The participant will be sedated. A flexible tube will be inserted through the nose or mouth into the lung airways. These participants will also have a physical exam, chest x-ray, and heart tests after the procedure.\n\n...",[354,355,356,357],"Alpha and Beta Thalassemia","Sickle Cell Disease","Malaria","Human Physiology",[359,356,355,354,312],"Assay Development",{"date":40,"type":41},{"date":362,"type":41},"2019-09-25",{"date":364,"type":22},"2029-03-31",{"name":47,"class":48},{"id":367,"slug":368,"hasResults":12,"nctId":369,"briefTitle":370,"officialTitle":371,"acronym":4,"eligibilityCriteria":372,"healthyVolunteers":12,"sex":17,"minAge":58,"maxAge":4,"enrollmentInfo":373,"targetDuration":4,"studyType":99,"phases":4,"briefSummary":374,"conditions":375,"keywords":378,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":381,"lastUpdatePostDateStruct":382,"startDateStruct":383,"completionDateStruct":385,"leadSponsor":387,"locationsCount":248},"100652880","expanding-hope-liver-100652880","NCT07778459","Expanding HOPE Liver","HOPE in Action Liver Transplantation From Donors With HIV: Impact on Opportunistic Infections, Cancer, and Long-Term Outcomes (Expanding HOPE Liver) (RTB-024)","Inclusion Criteria:\n\nRecipient Inclusion Criteria\n\n1. Participant meets local criteria for liver or simultaneous liver kidney (SLK) transplant\n2. Participant or legally authorized representative (in accordance with Johns Hopkins Medicine Institutional Review Board (IRB) and local IRB policy) is able to understand and provide informed consent\n3. Participant has documented HIV infection by any licensed assay or documented history of detectable Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA)\n4. Participant is ≥ 18 years old\n5. Most recent HIV-1 RNA \\\u003C= 50 copies RNA\u002FmL. Viral blips between 50-400 copies will be allowed as long as there are not consecutive measurements \\> 200 copies\u002FmL. Organ recipients who are unable to tolerate ART due to organ failure or recently started ART may have detectable viral load and still be eligible if a safe and effective antiretroviral regimen to be used by the recipient after transplantation is described\n\nDeceased Donor Criteria\n\n1. Donation after brain death or cardiac death\n2. Donors with HIV have confirmed or suspected HIV infection (by medical record history and licensed HIV test). If HIV infection is diagnosed during the donor evaluation process, a second confirmatory test will be required. Organs from donors with suspected false positive HIV screening tests can be used under this protocol\n3. Donor has no active opportunistic infections, neoplasms, and\u002For severe acute retroviral syndrome; if previous history of an opportunistic infection, donor has received appropriate treatment\n4. Donor may have any HIV-1 RNA viral load provided a safe, tolerable, and effective post-transplant antiretroviral regimen to be prescribed for the recipient is anticipated, described, and justified\n5. Donors with active hepatitis C virus infection (detectable HCV nucleic acid by licensed assay in a Clinical Laboratory Improvement Amendments (CLIA)-certified lab) are acceptable based on local site practice\n\nExclusion Criteria:\n\nRecipient\n\n1. Participant has prior progressive multifocal leukoencephalopathy (PML), cryptosporidiosis of \\> 1 month, or primary Central Nervous System (CNS) lymphoma\n2. Participant is pregnant or breastfeeding. Note: Participants who become pregnant post-transplant will be followed on study and managed per local site practice\n3. Past or current medical problems or findings from medical history, physical examination, or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study",{"count":128,"type":22},"This is a prospective, multicenter clinical study. The objective is to determine whether a liver transplant from a deceased donor with HIV is associated with an increased risk of opportunistic infection and cancer. Adults with Human Immunodeficiency Virus (HIV) in need of a liver or simultaneous liver-kidney (SLK) transplant who meet study-specified criteria will be offered enrollment in the study. The analytic plan includes an observational cohort of liver and SLK transplant recipients from prior HOPE in Action studies.",[376,377],"HIV Infection","Liver Transplant",[337,379,380],"Liver transplant","Deceased donor","2026-08-19",{"date":40,"type":41},{"date":384,"type":22},"2026-10-15",{"date":386,"type":22},"2030-08-31",{"name":47,"class":48},{"id":389,"slug":390,"hasResults":12,"nctId":391,"briefTitle":392,"officialTitle":393,"acronym":4,"eligibilityCriteria":394,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":395,"enrollmentInfo":396,"targetDuration":4,"studyType":23,"phases":398,"briefSummary":399,"conditions":400,"keywords":403,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":381,"lastUpdatePostDateStruct":409,"startDateStruct":410,"completionDateStruct":412,"leadSponsor":414,"locationsCount":49},"100601483","phase-1-quadrivalent-influenza-ha-stem-vaccine-vrc-flumos0122-00-vp-stemos1-with-and-without-alfq-adjuvant-in-healthy-adults-100601483","NCT07111078","Quadrivalent Influenza HA Stem Vaccine VRC-FLUMOS0122-00-VP (SteMos1) With and Without ALFQ Adjuvant in Healthy Adults","VRC 329: A Phase I Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Quadrivalent Influenza HA Stem Vaccine VRC-FLUMOS0122-00-VP (STEMos1) With and Without ALFQ Adjuvant in Healthy Adults","* INCLUSION CRITERIA:\n\nA participant must meet all of the following criteria:\n\n* Healthy adults between the ages of 18-50 years, inclusive\n* Based on history and physical examination, be in good general health and without a history of any of the conditions listed in the exclusion criteria\n* Received at least one licensed influenza vaccine from the 2020-2021 influenza season through the 2024-2025 influenza season\n* Able and willing to complete the informed consent process\n* The ability to read and comprehend English as all consent and recruitment materials are in English.\n* Available for clinic visits for 68 weeks after the first dose, including through the 2025-2026 influenza season\n* Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process\n* Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) \\\u003C= 35 within the 56 days before enrollment\n* Agrees to not receive any licensed influenza vaccination during study participation due to potential confounding of study results\n* Willing to have blood and mucosal samples collected, stored indefinitely, and used for research purposes.\n\nLaboratory Criteria within 56 days before enrollment:\n\n* WBC and differential within institutional normal range or accompanied by approval of the site Principal Investigator (PI) or designee\n* Total lymphocyte count \\>= 800 cells\u002Fmicroliter\n* Platelets = 125,000-400,000 cells\u002Fmircoliter\n* Hemoglobin within institutional normal range or accompanied by approval of the PI or designee\n* Alanine aminotransferase (ALT) \\\u003C= 1.25 x institutional upper limit of normal (ULN)\n* Aspartate aminotransferase (AST) \\\u003C= 1.25 x institutional ULN\n* Alkaline phosphatase (ALP) \\\u003C 1.1 x institutional ULN\n* Total bilirubin within institutional normal range or accompanied by approval of the PI or designee\n* Serum creatinine \\\u003C= 1.1 x institutional ULN\n* Negative for HIV infection by an FDA-approved method of detection\n\nCriteria applicable to women of childbearing potential:\n\n* Negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test (urine or serum) on the day of enrollment\n* Agrees to use an effective means of birth control from at least 21 days prior to enrollment through the end of the study\n\nEXCLUSION CRITERIA:\n\nParticipant will be excluded if one or more of the following conditions apply:\n\n-Women who are breast-feeding or planning to become pregnant during the study\n\nA participant has received any of the following substances:\n\n* Receipt of any licensed influenza vaccine or lab-confirmed influenza infection within 6 months prior to enrollment.\n* Plan to or are required to receive the 2025-2026 or 2026-2027 licensed influenza vaccines\n* Live attenuated vaccines within 4 weeks prior to enrollment\n* Inactivated vaccines within 2 weeks prior to enrollment\n* mRNA vaccines within 4 weeks prior to enrollment\n* Receipt of the HA ferritin influenza vaccine VRC-FLUNPF081-00-VP alone or in prime-boost regimens with VRC-FLUDNA082-00-VP (HA-F A\u002FSing, DNA A\u002FSing, VRC 316).\n* Receipt of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1, VRC 325)\n* Receipt of the mosaic hexavalent influenza vaccine VRC-FLUMOS0116-00-VP (FluMos-v2, VRC 326)\n* More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment\n* Blood products within 16 weeks prior to enrollment\n* Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study\n* Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule\n* Current anti-TB prophylaxis or therapy\n\nParticipant has a history of any of the following clinically significant conditions:\n\n* Serious reactions to vaccines that preclude receipt of the study vaccinations as determined by the PI or designee\n* Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema\n* Asthma that is not well controlled\n* Diabetes mellitus (type I or II), except for gestational diabetes\n* Thyroid disease that is not well controlled\n* Idiopathic urticaria within the past year\n* Immune-mediated diseases, such as autoimmune or autoinflammatory diseases, or immunodeficiencies\n* Hypertension that is not well controlled\n* Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws\n* Malignancy that is active or history of malignancy that is likely to recur during the period of the study\n* Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years\n* Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen\n* Guillain-Barr(SqrRoot)(Copyright) Syndrome\n* Any medical, social condition, occupational reason, or other reason that, in the judgment of the PI or designee, is a contraindication to protocol participation or impairs a participant's ability to give informed consent, including but not limited to clinically significant forms of infectious diseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, or heart disease.","50 Years",{"count":397,"type":22},56,[25],"Background:\n\nInfluenza (flu) is a contagious respiratory illness caused by viruses. Flu symptoms can range from mild to severe, and the illness can be fatal. Vaccines help the body learn to prevent or fight infections such as flu. Some vaccines are combined with adjuvants. Adjuvants are special salts or fats that help vaccines work better. Researchers are looking for ways to make flu vaccines more effective.\n\nObjective:\n\nTo test a new flu vaccine with and without a new adjuvant.\n\nEligibility:\n\nHealthy adults aged 18 to 50. They must have had at least 1 flu vaccine since 2020.\n\nDesign:\n\nParticipants will have 12 clinic visits over 15 months.\n\nThe vaccine is given as an injection into the muscle of the upper arm. Participants will be vaccinated during 2 visits spaced 4 months apart. Half will receive just the vaccine; half will receive the vaccine plus the adjuvant. They will be monitored for at least 30 minutes after each shot.\n\nParticipants will keep a diary for 7 days after each shot. They check their temperature every day and record any symptoms.\n\nParticipants will have 10 follow-up clinic visits plus 4 phone calls. They will have 4 to 10 tablespoons of blood drawn at each clinic visit. Fluid samples will be collected from their nose and mouth. They will be checked for any health changes.\n\nParticipants may opt to undergo apheresis: Blood will be taken from the body through a needle inserted into a vein. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be returned to the body through a different needle.",[401,402],"Influenza Prevention","Pandemic Influenza Prevention",[404,405,406,407,408,81],"Dose-Escalation","INFLUENZA VIRUS","Immune Response","Respiratory Illness","Experimental Vaccine",{"date":38,"type":41},{"date":411,"type":41},"2025-08-27",{"date":413,"type":22},"2027-08-18",{"name":47,"class":48},{"id":416,"slug":417,"hasResults":12,"nctId":418,"briefTitle":419,"officialTitle":420,"acronym":421,"eligibilityCriteria":422,"healthyVolunteers":57,"sex":17,"minAge":4,"maxAge":4,"enrollmentInfo":423,"targetDuration":425,"studyType":99,"phases":4,"briefSummary":426,"conditions":427,"keywords":429,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":381,"lastUpdatePostDateStruct":433,"startDateStruct":434,"completionDateStruct":436,"leadSponsor":438,"locationsCount":439},"100460178","registry-of-asthma-characterization-and-recruitment-3-racr3-100460178","NCT05272241","Registry of Asthma Characterization and Recruitment 3 (RACR3)","Registry of Asthma Characterization and Recruitment 3 (RACR3) (CAUSE-02)","RACR3","Inclusion Criteria:\n\n1. Participant is either:\n\n   1. At least 18 years old, willing and able to provide informed consent at the time of enrollment\n   2. Under the age of 18, accompanied by a legal guardian who is willing and able to provide informed consent at the time of enrollment\n2. Participant has a primary place of residence within the Office of Management and Budget (OMB)-defined Metropolitan Statistical Area (MSA)\n\nExclusion Criteria:\n\n1. Participant does not speak English or Spanish and\u002For guardian does not speak English or Spanish\n2. Participant does not have access to a phone, either personal or public, with regularity that could be used for scheduling and safety follow-up\n3. Past or current medical problems or findings from physical examination or laboratory testing, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may affect the quality or interpretation of the data obtained from the study\n\nParticipants who are pregnant or lactating will not be excluded or discontinued from the study, but will not undergo any procedures that are prohibited during pregnancy per the Childhood Asthma in Urban Settings 02 (CAUSE-02) Registry for Asthma Characterization and Recruitment 3 (RACR3) Manual of Procedures (MOP)(e.g., allergen skin testing, spirometry) during the pregnancy.\n\nPotential participants may be reassessed as outlined in the Protocol CAUSE-02 MOP.",{"count":424,"type":22},1500,"7 Years","This is a multi-center, non-interventional registry to create and maintain a database of participants to serve as a recruitment source for current and future DAIT NIAID-sponsored Childhood Asthma in Urban Settings (CAUSE) studies.",[428],"Asthma",[428,430,431,432],"Allergy","CAUSE","RACR",{"date":40,"type":41},{"date":435,"type":41},"2022-05-06",{"date":437,"type":22},"2027-05",{"name":47,"class":48},7,{"id":441,"slug":442,"hasResults":12,"nctId":443,"briefTitle":444,"officialTitle":445,"acronym":4,"eligibilityCriteria":446,"healthyVolunteers":12,"sex":17,"minAge":58,"maxAge":447,"enrollmentInfo":448,"targetDuration":4,"studyType":99,"phases":4,"briefSummary":449,"conditions":450,"keywords":452,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":381,"lastUpdatePostDateStruct":456,"startDateStruct":457,"completionDateStruct":459,"leadSponsor":461,"locationsCount":49},"100220464","pet-imaging-and-lymph-node-assessment-of-iris-in-people-with-aids-100220464","NCT02147405","PET Imaging and Lymph Node Assessment of IRIS in People With AIDS","PET Imaging and Lymph Node Assessment of IRIS in Persons With AIDS","* ELIGIBILITY CRITERIA:\n\nART NAIVE ARM INCLUSION CRITERIA:\n\n1. Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.\n2. No recent (within the past two years) treatment with combination anti-retroviral therapy (ART). Patients with limited (no more than 2-3 weeks) recent use of potent combination ART may be eligible for study participation if, the opinion of the investigator, the ART usage will not impact the scientific validity of the protocol\n3. Documented CD4+ cell count \\\u003C=100 cells\u002Fmm\\^3 within the past 8 weeks.\n4. Residence within the wider Washington D.C. area (within a 100-mile radius from the NIH Bethesda campus) and plans to stay in the area for 48 weeks\n5. Men or women age \\>=18 years.\n6. Ability and willingness of subject (or legal guardian\u002Frepresentative) to understand study requirements and give informed consent\\*.\n7. Willingness to allow storage of blood or tissue samples for future research\n8. Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, optional FDG-PET\u002FCT and lymph node biopsy)\n9. Willingness to have genetic testing\n10. Participants should have a primary care physician or will need to agree to have one established by 24 weeks on study.\n\n    * Potential participants who lack decision-making capacity to consent to research participation may enroll in this study at the discretion of the investigator if this incapacity is expected to last for a short period of time.\n\nIRIS ARM INCLUSION CRITERIA:\n\n1. Documentation of HIV-1 infection. Results from outside facilities will be accepted for enrollment.\n2. Meet criteria suspicious for IRIS (Must meet 4\u002F5 following criteria):\n\n   1. Initiation (reintroduction or change) in antiretroviral therapy\u002Fregimen\n   2. Evidence of:\n\n   i. an increase in CD4+ cell count defined as \\>= 50cell\u002Fmm\\^3 or a \\>= 2 fold rise in CD4+ cell count, and\u002For\n\n   ii. decrease in the HIV-1 viral load of \\>=0.5 log10\n\n   c. Symptoms and\u002For signs consistent with an infectious\u002Finflammatory condition.\n\n   d. These symptoms and\u002For signs cannot be explained by a newly acquired infection, the expected clinical course of a previously recognized infectious agent, or the side effects of antiretroviral therapy itself.\n\n   e. The infectious\u002Finflammatory condition must be attributable to a specific pathogen or condition.\n\n   Criteria d or e may not be met for suspected IRIS definition.\n3. Residence within the wider Washington D.C. area (within a 100-mile radius from the NIH Bethesda campus) \\*\\*Participants from outside of the 100 mile radius may be enrolled on a case by case basis to diagnose or manage IRIS.\n4. Men or women age \\>=18 years.\n5. Ability and willingness of subject to understand study requirements and give informed consent\\*.\n6. Willingness to allow storage of blood or tissue samples for future research\n7. Willingness at time of screening to undergo study procedures (phlebotomy, apheresis, an optional FDG-PET\u002FCT, and lymph node biopsy)\n8. Willingness to have genetic testing\n9. Participants should have a primary care physician who will initiate the referral.\n\n   * Potential participants who lack decision-making capacity to consent to research participation may enroll in this study at the discretion of the investigator if this incapacity is expected to last for a short period of time.\n\nSUBJECT EXCLUSION CRITERIA:\n\n1. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.\n2. Pregnancy will be an exclusion criterion for study entry given the intense nature of the protocol regarding blood draws, apheresis, biopsies and FDG-PET\u002FCT imaging.\n3. Inadequate venous access for phlebotomy and apheresis procedures as assessed by the study team.\n4. Women who are breastfeeding.\n5. A life-threatening underlying illness that according to the study team requires immediate intervention such as PML requiring initiation of ARVs or lymphomas requiring chemotherapy initiation.\n6. An inability to consent that is estimated by the study team to be irreversible.\n7. History of significant medical non-adherence which would, in the opinion of the investigator, interfere with study participation.","100 Years",{"count":351,"type":22},"Background:\n\n\\- Sometimes people with HIV, the virus that causes AIDS, can have new or worsening symptoms soon after starting HIV medications. Often these symptoms are caused by immune reconstitution inflammatory syndrome (IRIS). Researchers want to study why and how people develop IRIS and how best to prevent and treat it.\n\nObjectives:\n\n\\- To learn the causes and effects of IRIS, and how to best manage it.\n\nEligibility:\n\n\\- Adults 18 and older with HIV and low CD4 counts,, about to start HIV medicines; or those already taking HIV medicines with symptoms thought to be related to IRIS.\n\nDesign:\n\n* Participants not on ART will have screening blood tests for CD4 count, HIV viral load and genetic testing.\n* After the screening blood tests and before starting HIV medicines., participants will return for more than 1 visit for the following:\n* review of medical history\\\u003CTAB\\>\n* physical and eye exams\n* blood, urine, and tuberculosis (TB) tests\n* electrocardiogram (EKG)\n* chest x-ray\n* apheresis: a blood drawing procedure where blood is removed from a vein, white blood cells are separated and collected, and the rest of the blood is returned to the person using another vein\n* \\- PET scan - a procedure where a small amount of radioactive material is injected in a vein. The participant then lies on a table that slides into a scanner which takes images of the body.\n* lymph node biopsy\n* stool collection by swab\n* After completion of the above, HIV medicines will be started.\n* Follow-up visits will be at 2, 4, 8, and 12 weeks after starting ART, then every 12 weeks. Some of the tests above may be repeated.\n* Participants already on HIV medicines who may have IRIS will be screened over a 4 week time period to see if they really are experiencing IRIS. The screening process will include all of the items listed above. Follow-up visits will be at Weeks, 4, 8, 12 and then every 12 weeks.\n* The study will last 1 year for both groups but may be extended to 2 years (3 additional appointments) for some participants....",[451],"Immune Reconstitution Inflammatory Syndrome",[453,454,455,312],"FDG PET\u002FCT Scan","Lymph Node Biopsy","Apheresis",{"date":38,"type":41},{"date":458,"type":41},"2014-05-30",{"date":460,"type":22},"2030-04-30",{"name":47,"class":48},{"id":463,"slug":464,"hasResults":12,"nctId":465,"briefTitle":466,"officialTitle":467,"acronym":4,"eligibilityCriteria":468,"healthyVolunteers":12,"sex":17,"minAge":58,"maxAge":96,"enrollmentInfo":469,"targetDuration":4,"studyType":23,"phases":471,"briefSummary":472,"conditions":473,"keywords":475,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":480,"lastUpdatePostDateStruct":481,"startDateStruct":482,"completionDateStruct":484,"leadSponsor":486,"locationsCount":49},"100552789","phase-2-dupilumab-as-add-on-therapy-for-hypereosinophilic-syndrome-with-partial-clinical-response-to-eosinophil-depleting-biologic-agents-100552789","NCT06477653","Dupilumab as Add-On Therapy for Hypereosinophilic Syndrome With Partial Clinical Response to Eosinophil-Depleting Biologic Agents","A Pilot Phase 2 Study of the Safety and Efficacy of Dupilumab as Add-on Therapy for Hypereosinophilic Syndrome With Partial Clinical Response to Eosinophil-Depleting Biologic Agents","* INCLUSION CRITERIA:\n\nTo be eligible to participate in this study, an individual must meet all the following criteria:\n\n1. Age \\>=18 years\n2. Documented diagnosis of HES with historic AEC\\>1.5x10\\^9\u002FL on two occasions, no secondary etiology for the eosinophilia despite careful clinical evaluation, and evidence of end organ damage (histologic evidence of tissue infiltration by eosinophils and\u002For objective evidence of clinical pathology in any organ system that is temporally associated with eosinophilia and not clearly attributable to another cause)\n3. Currently receiving treatment with an eosinophil-lowering biologic (mepolizumab, reslizumab, or benralizumab) for a minimum of 24 weeks\n4. AEC\\\u003C0.5x10\\^9\u002FL\n5. Residual symptoms after a minimum of 24 weeks of eosinophil-lowering biologic therapy with at least 1 most bothersome symptom of moderate severity (HES-SI score \\>=2) consistent with \\>=1 of the following diagnoses:\n\n   a. asthma, defined as physician-documented asthma requiring medium to high dose inhaled corticosteroids + long-acting beta agonist b. atopic dermatitis, defined as physician-documented chronic or recurrent inflammatory skin disease\n\n   c. CRSwNP, defined as evidence of rhinosinusitis and nasal polyposis on physical examination or imaging\n\n   d. EoE, defined as biopsy-proven esophageal eosinophilia \\>15 eosinophils\u002Fhigh power field\n6. For participants who can become pregnant: sexual abstinence or use of highly effective contraception (i.e., partner vasectomy, bilateral tubal ligation, IUD, progestin implants, and other hormonal methods) starting 4 weeks prior to study drug initiation and agreement to use such a method during study participation and for an additional 12 weeks after the end of study drug administration\n7. Participation in NIH protocol 94-I-0079 (Activation and function of eosinophils in conditions with blood or tissue eosinophilia)\n8. Ability of subject to understand and the willingness to sign a written informed consent document\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n1. Pregnancy or lactation\n2. Known allergic reaction to dupilumab or any of the excipients in Dupixent(TM)\n3. Febrile illness within 7 days of enrollment\n4. Treatment with an investigational drug or other intervention other than mepolizumab, reslizumab, or benralizumab within 12 weeks or 4 half-lives of the investigational agent (whichever is longer).\n5. Known or suspected acquired or inborn immunodeficiency disorder, including HIV infection\n6. Known diagnosis of eosinophilic granulomatosis with polyangiitis\n7. Change in eosinophil-active therapy within the past 6 weeks, including but not limited to topical corticosteroids, leukotriene inhibitors, initiation or change of a food-elimination diet regimen or re-introduction of a previously eliminated food (in patients with gastrointestinal involvement), and proton pump inhibitors (in patients with gastrointestinal involvement)\n8. Planned or anticipated major surgical procedure during the study\n9. Active parasitic infection\n10. History of malignancy within 5 years, excluding completely treated in situ carcinoma of the cervix, or squamous or basal cell carcinoma of the skin\n11. Any condition that, in the investigator s opinion, places the patient at undue risk by participating in the study\n\nFor patients with eosinophilic gastrointestinal disease only:\n\n1. Active infection with Helicobacter pylori\n2. History of achalasia, Crohn s disease, ulcerative colitis, celiac disease, or prior esophageal surgery\n3. Any esophageal stricture unable to be passed with a standard, diagnostic, 9 to 10 mm upper endoscope",{"count":470,"type":22},30,[26],"Background:\n\nHypereosinophilic syndrome (HES) is a blood disorder that causes high levels of white blood cells called eosinophils. HES can damage the lungs and airways, intestines, skin, and other organs. The current primary treatment for HES can cause serious side effects. Secondary treatments do not work in all people.\n\nObjective:\n\nTo test an approved drug (dupilumab), combined with other drugs, in people with HES.\n\nEligibility:\n\nPeople aged 18 years and older who take drugs (mepolizumab, reslizumab, or benralizumab) to treat HES.\n\nDesign:\n\nParticipants will have up to 6 clinic visits and 7 remote visits in up to 48 weeks.\n\nParticipants will be screened. They will have blood and urine tests. They will have a test of their heart function. They will take surveys about how HES affects their daily life. Some participants may have a bone marrow biopsy: A sample of tissue and fluid from inside a bone will be removed with a large needle.\n\nParticipants will have other tests specific to their symptoms. For example, those with symptoms affecting their lungs will have breathing tests. Others may have tests that target symptoms in their sinuses, gastrointestinal tract, or skin.\n\nDupilumab is injected under the skin once every 1 or 2 weeks. Dose and timing will vary among participants. They will be taught how to inject themselves at home between clinic visits. They will take dupilumab plus their current medications for 24 weeks. If the drug is helping them, they will continue taking it for another 24 weeks.\n\nParticipants will have a final visit 12 weeks after their last dose.",[474],"Hypereosinophilic Syndrome",[474,476,477,478,479],"Eosinophil","Monoclonal Antibody","Clinical Trial","Treatment","2026-08-18",{"date":381,"type":41},{"date":483,"type":41},"2025-02-05",{"date":485,"type":22},"2027-03-30",{"name":47,"class":48},{"id":488,"slug":489,"hasResults":12,"nctId":490,"briefTitle":491,"officialTitle":491,"acronym":4,"eligibilityCriteria":492,"healthyVolunteers":57,"sex":17,"minAge":58,"maxAge":349,"enrollmentInfo":493,"targetDuration":4,"studyType":99,"phases":4,"briefSummary":495,"conditions":496,"keywords":502,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":480,"lastUpdatePostDateStruct":508,"startDateStruct":509,"completionDateStruct":4,"leadSponsor":511,"locationsCount":49},"100054446","recruitment-and-apheresis-collection-of-peripheral-blood-hematopoietic-stem-cells-mononuclear-cells-and-granulocytes-100054446","NCT00001405","Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells, Mononuclear Cells and Granulocytes","* ELIGIBILITY CRITERIA:\n\nPatients (Patients with a genetically defined PID or other blood disorder or clinical history consistent with PID or other blood disorder)\n\n1. Patients will have a genetically defined PID or have a clinical history of recurrent infections or other problems suggestive of PID or other blood disorder, must be 18-70 years of age,\n2. Some patients may have active bacterial or fungal infection at the time of study entry.\n3. Preserved renal function (creatinine less than or equal to 2.5 mg\u002FdL; less than or equal to 3+ proteinuria); preserved hepatic function (bilirubin less than or equal to 2.0 mg\u002Fdl); preserved hematologic function (WBC greater than or equal to1000\u002Fmm\\^3;granulocytes greater than or equal to 500\u002Fmm\\^3; platelets greater than or equal to 100,000; hematocrit greater than or equal to 25). Of note, patients with PID often have associated chronic thrombocytopenia. Patients with stable chronic thrombocytopenia will be eligible for collection, at the investigator s discretion, with the caveat that patients with platelet count \\\u003C40,000 the day prior to collection will be transfused with platelets on the morning of collection. Platelets may also be given to these patients following the collection if medically indicated..\n4. Patients of childbearing potential may be entered if using effective contraception and having a negative serum or urine pregnancy test within one week of beginning G-CSF administration.\n5. Patients may remain on their regimen of prophylactic treatments as deemed necessary by the investigator.\n6. Willingness to allow blood cell samples to be stored\n7. Willingness to allow blood and\u002For bone marrow samples to be modified to iPS cells\n\nHealthy Adult Volunteers\n\n1. Healthy adults aged 18-65 without active current infection or history of recurrent infection,\n2. Weighs at least 50kg.\n3. Normal renal function (creatinine less than or equal to 1.5 mg\u002FdL; less than or equal to 1+ proteinuria); normal hepatic function (bilirubin less than or equal to 1.5 mg\u002FdL); normal hematologic function (WBC greater than or equal to 2500\u002Fmm\\^3; granulocytes greater than or equal to 1200\u002Fmm\\^3; platelets greater than or equal to 120,000; hematocrit greater than or equal to 38).\n4. Normal female volunteers of childbearing potential may be entered if using effective contraception and having a negative serum or urine pregnancy test within one week of beginning GCSF administration.\n5. Willingness to allow blood cell samples to be stored\n6. Willingness to allow blood and\u002For bone marrow samples to be modified to iPS cells\n\nFor PBMCs and grans collections, adult subjects with known genetic mutations may participate as healthy volunteers for research purposes as long as the other criteria listed above are fulfilled.\n\nEXCLUSIONS:\n\nPatients\n\n1. Patients who are hemodynamically unstable (systolic or diastolic blood pressure fall of 20 mm Hg from the stable patient s baseline measurement) or requiring mechanical respiratory assistance are excluded.\n2. Female patients who are pregnant or lactating as determined by history and\u002For positive pregnancy test are excluded.\n3. Must be negative by routine blood donor eligibility testing criteria including tests for syphilis (RPR) and TTV Donor Transplant Panel testing (list is modified periodically, but may include hepatitis B and C, HIV and HTLV, T. cruzi). This does not apply to leukapheresis patients, as these tests are not required by DTM.\n\n   1. XSCID patients do not make antibodies and false positives may occur because they receive periodic infusions of pooled donations of IVIG. We have observed positive anti-HBc testing in these patients. If this occurs, more specific DNA or antigen testing will be done and must be negative.\n   2. Patients with CGD and other patients with autoimmunity as part of their PID phenotype may have false positive antibody tests and if this occurs more specific DNA or antigen testing will be done and must be negative.\n   3. Autologous HSC Transplant patients - may be positive for Hepatitis B and C if the investigator deems it necessary to be collected and used as a safety back-up\n\nHealthy Volunteers\n\n1. Active bacterial, fungal or viral infection as evidenced by history, physical exam (temperature \\>38 degress C), or WBC \\>9000 are excluded.\n2. Females who are pregnant or lactating as determined by history and\u002For pregnancy test are excluded.\n3. Must be negative by routine blood donor eligibility testing criteria, including tests for syphilis (RPR) and TTV Recipient Transplant Panel (list is modified periodically, but may include hepatitis B and C, HIV and HTLV, T. cruzi) This does not apply to leukaphersis patients, as these tests are not required by DTM policy.\n4. Someone without peripheral venous access in arm veins adequate for apheresis (healthy volunteers only).\n5. If in the opinion of the investigator participation in this study places the healthy adult volunteer at undue risk.\n\nPatients being considered for clinical scale bone marrow harvesting\n\n1. Who are unable to lie prone during the bone marrow harvesting procedure.\n2. Who are unable to tolerate general anesthesia during the bone marrow harvesting procedure.",{"count":494,"type":22},850,"The research goal of this study is to obtain CD34+ hematopoietic stem cells (HSC) from peripheral blood and\u002For bone marrow, and Mononuclear Cells (lymphocytes and monocytes), and granulocytes (grans) from peripheral blood that will be used in the laboratory and\u002For in the clinic to develop new cell therapies for patients with inherited or acquired disorders of immunity or blood cells. Development of novel cellular therapies requires access to HSC, Mononuclear Cells and\u002For granulocytes as the essential starting materials for the pre-clinical laboratory development of gene therapies and other engineered cell products. HSC or blood cells from healthy adult volunteers serve both as necessary experimental controls and also as surrogates for patient cells for clinical scale-up development. HSC or blood cells from patients serve both as the necessary experimental substrate for novel gene therapy and cellular engineering development for specific disorders and as pre-clinical scale up of cellular therapies. Collection of cells from adult patients collected in the NIH Department of Transfusion Medicine (DTM) under conditions conforming to accepted blood banking clinical practice may also be used directly in or cryopreserved for future use in other NIH protocols that have all required regulatory approvals allowing such use. In summary, the research goal of this protocol is the collection of HSC or blood cells that may be used for both laboratory research and\u002For for clinical treatment in other approved protocols.",[497,498,499,500,501],"Granuloma","Granulomatous Disease, Chronic","Leukocyte Disease","Genetic Disease, X-Linked","Genetic Disease, Inborn",[503,504,505,506,331,312,507],"Chronic Granulomatous Disease","CD34 Cells","Infection","Nadph Oxidase","Normal Volunteer",{"date":381,"type":41},{"date":510,"type":41},"1994-02-27",{"name":47,"class":48},{"id":513,"slug":514,"hasResults":12,"nctId":515,"briefTitle":516,"officialTitle":517,"acronym":4,"eligibilityCriteria":518,"healthyVolunteers":12,"sex":17,"minAge":519,"maxAge":4,"enrollmentInfo":520,"targetDuration":4,"studyType":23,"phases":522,"briefSummary":523,"conditions":524,"keywords":526,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":535,"lastUpdatePostDateStruct":536,"startDateStruct":537,"completionDateStruct":539,"leadSponsor":541,"locationsCount":542},"100641915","phase-2-a-trial-of-stratified-patient-centered-treatment-regimens-for-active-tb-spectra-tb-100641915","NCT07595042","A Trial of Stratified Patient-Centered Treatment Regimens for Active TB (SPECTRA-TB)","A Phase 2C Trial of Stratified Patient-Centered Treatment Regimens for Active TB","Inclusion Criteria:\n\n* Has pulmonary tuberculosis (TB) that is likely to respond to standard TB medicines (drug-susceptible TB), based on sputum testing done within 7 days before entering the study. The test must show Mycobacterium tuberculosis is present, with no rifamycin resistance detected and no known resistance to isoniazid or fluoroquinolones.\n* Has a SPECTRA-TB risk score and risk group assigned during screening using the study-specific calculator.\n* Has a Karnofsky performance score of 50 or higher within 30 days before entering the study.\n* Has documented HIV-1 status (either with HIV or without HIV) based on acceptable testing.\n* If living with HIV, has a CD4+ cell count of at least 50 cells\u002Fmm3 within 60 days before study entry.\n* If living with HIV, is currently receiving or plans to start an efavirenz-based or dolutegravir-based antiretroviral therapy regimen by study week 8.\n* Has laboratory test results within 7 days before study entry that meet all of the following:\n\n  * alanine aminotransferase (ALT) no more than 3 times the upper limit of normal\n  * total bilirubin no more than 2.5 times the upper limit of normal\n  * creatinine no more than 2 times the upper limit of normal\n  * potassium between 3.5 and 5.5 mEq\u002FL\n  * absolute neutrophil count at least 1000\u002Fmm3\n  * hemoglobin at least 7.0 g\u002FdL\n  * platelet count at least 100,000\u002Fmm3\n* If able to become pregnant, has a negative blood or urine pregnancy test within 7 days before study entry.\n* If able to become pregnant and sexually active in a way that could lead to pregnancy, agrees not to try to become pregnant and agrees to use at least 1 reliable non-hormonal birth control method during study treatment and for 30 days after stopping study drugs. Acceptable methods include:\n\n  * condoms\n  * intrauterine device (IUD) or intrauterine system (IUS)\n  * cervical cap with spermicide\n  * diaphragm with spermicide\n* If not able to become pregnant, has a history or documentation of menopause, hysterectomy, bilateral removal of the ovaries, or bilateral tubal ligation.\n* Has a verifiable address or place of residence and is willing to tell the study team about any change of address during treatment and follow-up.\n* Is willing and able to give informed consent, or assent with permission from a parent or legal guardian if required.\n\nExclusion Criteria:\n\n* TB bacteria are known to be resistant to 1 or more of the following medicines: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.\n* Received more than 5 days of treatment for active TB within the 24 weeks before study entry.\n* Received more than 5 days of treatment within the 30 days before study entry with certain TB medicines or related antibiotics, including isoniazid, rifampin, rifapentine, ethambutol, moxifloxacin, pyrazinamide, aminoglycosides, fluoroquinolones, linezolid, bedaquiline, pretomanid, and other specified anti-TB drugs.\n* Has suspected or confirmed TB involving the brain or central nervous system, bones, joints, heart lining (pericardium), or miliary TB.\n* Has a past history of suspected or confirmed drug-resistant TB of any type.\n* Is currently pregnant or breastfeeding.\n* Cannot take medicines by mouth.\n* Has an HIV\u002FAIDS-related opportunistic infection at study entry.\n* Has acute or chronic hepatitis B, unless the hepatitis B infection has cleared.\n* Has acute or chronic hepatitis C, unless the hepatitis C infection has cleared or has been successfully treated.\n* Has alcohol-related liver disease.\n* Has liver cirrhosis.\n* Has a history of aortic aneurysm or aortic dissection.\n* Has a known history of long QT syndrome, a first-degree relative with long QT syndrome, or a screening ECG showing QTcF greater than 470 ms that does not correct with treatment of contributing factors.\n* Is taking other medicines that can prolong the QT interval and cannot safely switch to an alternative medicine.\n* Has a known history of acute intermittent porphyria.\n* Weighs less than 30 kg.\n* Is currently using, or is expected to need within 24 weeks after enrollment, 1 or more medicines that are not allowed during the study.\n* Has a known allergy, sensitivity, or hypersensitivity to any of the study drugs or their ingredients.\n* Has active drug or alcohol use, dependence, mental illness, or another serious infection that, in the opinion of the site investigator, could make it hard to follow the study requirements.\n* Is currently taking part in another interventional clinical trial.","13 Years",{"count":521,"type":22},900,[26],"The A5414 study will evaluate whether treatment for drug-susceptible pulmonary tuberculosis (TB) can be tailored according to a participant's risk of an unfavorable outcome. Participants will be assigned to lower-risk or higher-risk groups using baseline characteristics and then randomized within each group to receive either standard TB treatment or an investigational rifapentine- and moxifloxacin-containing regimen. The study will evaluate whether shorter treatment durations may be used in lower-risk participants and whether the investigational regimen may improve outcomes in higher-risk participants. Safety and tolerability will also be evaluated.",[525],"Tuberculosis",[525,527,528,529,530,531,532,533,534],"Pulmonary tuberculosis","Drug-susceptible tuberculosis","Rifampin-susceptible tuberculosis","Rifapentine","Moxifloxacin","HIV coinfection","Treatment shortening","Risk-stratified treatment","2026-08-17",{"date":381,"type":41},{"date":538,"type":22},"2026-10-30",{"date":540,"type":22},"2029-10-22",{"name":47,"class":48},29,{"id":544,"slug":545,"hasResults":12,"nctId":546,"briefTitle":547,"officialTitle":548,"acronym":4,"eligibilityCriteria":549,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":519,"enrollmentInfo":550,"targetDuration":4,"studyType":23,"phases":552,"briefSummary":553,"conditions":554,"keywords":555,"overallStatus":37,"whyStopped":4,"lastUpdateSubmitDate":535,"lastUpdatePostDateStruct":557,"startDateStruct":558,"completionDateStruct":559,"leadSponsor":561,"locationsCount":562},"100602518","phase-1-a-study-of-daily-rifapentine-combined-with-isoniazid-1hp-for-tuberculosis-prevention-in-children-less-than-13-years-of-age-with-and-without-hiv-100602518","NCT07124559","A Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV","Phase I\u002FII Dose Finding, Safety and Tolerability Study of Daily Rifapentine Combined With Isoniazid (1HP) for Tuberculosis Prevention in Children Less Than 13 Years of Age With and Without HIV","Inclusion Criteria:\n\n1. A parent or legal guardian must be willing and able to give written permission for the child to participate in the study. If required by local policies, the child must also be willing and able to give written assent to participate. All sites must follow local policies and procedures.\n2. Age requirements at entry:\n\n   * Cohort 1: Children under 13 years old.\n   * Cohort 2: Children aged 12 weeks to under 13 years old.\n3. For Cohort 1 participants under 28 days old: The child must have been born at or after 37 weeks of pregnancy, as determined by the site investigator using parent\u002Fguardian report or medical records.\n4. Weight requirements at entry:\n\n   * Cohort 1: 3 kg to under 45 kg.\n   * Cohort 2: 6 kg to under 45 kg.\n5. HIV status:\n\n   * Cohort 1: Must be living without HIV.\n   * Cohort 2: Must be living with HIV.\n6. At risk of TB disease, defined as meeting at least one of the following:\n\n   * Having close contact with someone with infectious pulmonary TB within the past six months.\n   * A positive tuberculin skin test (TST) or, for those over two years old, a positive interferon gamma release assay (IGRA) if TST is not available.\n   * For Cohort 2 only: Living in a high TB burden area (≥ 60 TB cases per 100,000 people per year).\n7. Normal or mild (grade 1 or 2) test results for the following at screening (within 21 days before entry):\n\n   * ALT (liver enzyme)\n   * Estimated glomerular filtration rate (kidney function)\n   * Absolute neutrophil count (white blood cells)\n   * Hemoglobin (red blood cells)\n8. For Cohort 2 participants:\n\n   * Must have been on antiretroviral therapy (ART) for at least 12 weeks before entry.\n   * Must have been on a specific ART regimen (once-daily DTG and two NRTIs) for at least 14 days before entry.\n   * Must have used the same formulation of DTG (tablet or dispersible tablet) for at least three days before entry.\n   * Must agree to continue the same formulation of DTG for the study duration.\n   * Must have an HIV-1 RNA level below 200 copies\u002FmL at screening.\n9. Must intend to stay in the same area for the study duration.\n10. Must have access to at least one meal per day during the 28-day treatment period.\n\nExclusion Criteria:\n\n1. The child has active TB, confirmed by medical records, parent\u002Fguardian report, or tests during screening, indicated by:\n\n   * Currently being treated for active TB.\n   * Symptoms like poor growth, poor weight gain, weight loss, cough for at least 11 days, or fever for at least eight days.\n   * X-ray or CT scan showing TB.\n   * Positive TB test results (e.g., culture, Xpert MTB\u002FRIF Ultra, Truenat M.tb, other nucleic acid tests, urine tests).\n2. The child has been exposed to an adult with drug-resistant TB (resistant to Rifampicin or Isoniazid) within the past six months.\n3. The child has taken the following medications:\n\n   * Daily Isoniazid in the 28 days before entry.\n   * Any prohibited medications listed in the study within three days before entry.\n4. The child has any of the following conditions:\n\n   * Acute or chronic hepatitis.\n   * Allergy to Isoniazid or rifamycins.\n   * Porphyria.\n   * Severe peripheral neuropathy.\n5. The child has severe acute malnutrition (weight-for-height\u002Flength less than -3 z-scores of WHO standards). Note: Children who are stunted (height-for-age more than two standard deviations below WHO standards) are eligible.\n6. For Cohort 2: The child has an active AIDS-defining opportunistic infection.\n7. The child has started menstruation.\n8. The child has taken NVP, EFV, lopinavir\u002Fritonavir, and\u002For raltegravir within 14 days before entry.\n9. The child has received long-term immunosuppressive therapy (more than eight days) within 30 days before entry. Note: Short courses of steroids (seven days or less) may be allowed with approval.\n10. The child is a result of a multiple birth (e.g., twins, triplets).\n11. The child has any other significant medical condition that would make participation unsafe, complicate data interpretation, or interfere with study objectives, as determined by the site investigator.",{"count":551,"type":22},144,[25,26],"This study aims to find the proposed dose of Rifapentine (RPT) taken once daily with Isoniazid (INH) for 28 days to prevent tuberculosis (TB). The study will take place at multiple locations and children under 13 years old will be divided into two groups: one group will include children without HIV, and the other group will include children with HIV who are on antiretroviral treatment. Up to 144 children will participate, and participants in each group will be followed for 24 weeks.",[525],[337,525,556],"Latent Tuberculosis",{"date":381,"type":41},{"date":384,"type":22},{"date":560,"type":22},"2028-05-31",{"name":47,"class":48},11,{"id":564,"slug":565,"hasResults":12,"nctId":566,"briefTitle":567,"officialTitle":568,"acronym":569,"eligibilityCriteria":570,"healthyVolunteers":12,"sex":17,"minAge":58,"maxAge":4,"enrollmentInfo":571,"targetDuration":4,"studyType":23,"phases":573,"briefSummary":574,"conditions":575,"keywords":4,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":535,"lastUpdatePostDateStruct":577,"startDateStruct":578,"completionDateStruct":580,"leadSponsor":582,"locationsCount":542},"100530851","phase-2-trial-of-novel-regimens-for-the-treatment-of-pulmonary-tuberculosis-100530851","NCT06192160","Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis","A Phase 2 Randomized, Adaptive, Dose-Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis","RAD-TB","Inclusion Criteria:\n\n1. Pulmonary TB (among individuals either without history of prior TB treatment or with history of TB treatment completed more than 2 years prior to study entry), identified within 7 days prior to study entry by at least one sputum specimen positive for Mtb by Xpert. Semiquantitative Mtb results of \"medium\" or \"high\" from Xpert MTB\u002FRIF Ultra are required.\n2. Pulmonary TB with documented INH susceptibility (by Line Probe Assay (LPA) or Xpert MTB\u002FXDR or other validated molecular test) and with documented RIF susceptibility (by LPA or Xpert MTB\u002FRIF or Xpert MTB\u002FRIF Ultra or other validated molecular test) within 7 days prior to study entry.\n3. Documentation of HIV-1 infection status, as below:\n\n   Presence or absence of HIV-1 infection, as documented by:\n   * Any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E\u002FCIA) test kit, any time prior to study entry. AND for a positive result confirmation by one of the following:\n   * A second antibody test from different manufacturers or based on different principles and epitopes (combination antigen-antibody-based rapid tests may be used), or\n   * HIV-1 antigen, or\n   * Plasma HIV-1 RNA viral load, or\n   * A licensed Western blot\n4. For individuals with HIV: CD4+ cell count ≥100 cells\u002Fmm3 based on testing performed within 30 days prior to study entry.\n5. For individuals with HIV: Currently being treated with dolutegravir-based antiretroviral therapy (ART), or plan to initiate dolutegravir-based ART at or before study week 8.\n6. Individuals age ≥18 years.\n7. The following laboratory values obtained within 7 days prior to study entry at any network-approved non-U.S. laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs:\n\n   * Serum or plasma alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)\n   * Serum or plasma total bilirubin ≤2 times ULN\n   * Serum or plasma creatinine ≤2 times ULN\n   * Serum or plasma potassium ≥3.5 mEq\u002FL\n   * Serum or plasma magnesium ≥1.0 mEq\u002FL (≥0.500 mmol\u002FL)\n   * Absolute neutrophil count (ANC) ≥1500\u002Fmm\\^3\n   * Hemoglobin ≥9.0 g\u002FdL\n   * Platelet count ≥100,000\u002Fmm\\^3\n   * Negative for, hepatitis B surface antigen (HBsAg)\n   * Negative for hepatitis C virus (HCV) antibody (or if HCV antibody positive, must have a negative HCV PCR)\n8. For female study candidates who are of reproductive potential, negative pregnancy test (urine HCG or serum β-HCG) within 3 days (72 hours) prior to entry by any network-approved non-U.S. laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs.\n\n   Females who are of reproductive potential and who participate in sexual activity that could lead to pregnancy must agree to use at least two of the following forms of birth control while receiving TB study medications and for 12 months after stopping study medications:\n   * Male or female condoms\n   * Diaphragm or cervical cap (with spermicide, if available)\n   * Intrauterine device (IUD) or intrauterine system (IUS)\n   * Hormone-based birth control (e.g., oral contraceptives, Depo-Provera, NuvaRing, implants)\n\n   Female study candidates who are of reproductive potential, but who abstain from sexual activity that could lead to pregnancy require no additional contraception.\n\n   Female study candidates who are not of reproductive potential are eligible without requiring the use of contraceptives. Self-reported history is acceptable documentation of menopause (i.e., at least 1 year amenorrheic), hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; these candidates are all considered not of reproductive potential.\n9. For male study candidates who engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives. They are also strongly advised to inform their non-pregnant sexual partners of reproductive potential to use effective contraceptives while the individual is on study and for 90 days after experimental treatment discontinuation.\n\n   For male study candidates who have undergone successful vasectomy with documented azoospermia or have documented azoospermia for any other reason, are eligible without requiring the use of contraceptives.\n10. For male study candidates with pregnant partners, willingness to use condoms during vaginal intercourse while on study and for 90 days after experimental treatment discontinuation.\n11. For male study candidates, willingness to refrain from sperm donation while on study and for 90 days after experimental treatment discontinuation.\n12. Documentation of Karnofsky performance score ≥60 obtained within 14 days prior to study entry.\n13. Chest x-ray obtained within 14 days prior to study entry.\n14. A verifiable address or residence readily accessible for visiting, and willingness to inform the study team of any change of address during study treatment and follow-up period.\n15. Ability and willingness of individual to provide informed consent.\n\nExclusion Criteria:\n\n1. More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry.\n2. Current extrapulmonary TB, in the opinion of the investigator.\n3. QTcF interval \\>450 ms within 7 days prior to study entry.\n4. History of or ongoing heart failure.\n5. Personal or family history of congenital QT prolongation.\n6. History of known, untreated, ongoing hypothyroidism.\n7. History of or ongoing bradyarrhythmia.\n8. History of torsades de pointes.\n9. Current Grade 2 or higher peripheral neuropathy.\n10. Other medical conditions (e.g., diabetes, liver or kidney disease, blood disorders, chronic diarrhea), in the opinion of the site investigator, in which the current clinical condition of the participant is likely to prejudice the response to, or assessment of, treatment.\n11. Pregnant or breastfeeding or planning to become pregnant within the next 12 months.\n12. Weight \\\u003C35 kg.\n13. Unable to take oral medications.\n14. Taking any of prohibited medications.\n15. Known allergy\u002Fsensitivity or any hypersensitivity to components of investigational agents or their formulation.\n16. Active drug or alcohol use or dependence; or mental illness (e.g., major depression) that, in the opinion of the site investigator, would interfere with adherence to study requirements.\n17. Taking an investigational drug or vaccine within 30 or more days prior to study entry.",{"count":572,"type":22},315,[26],"A5409\u002FRAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB).\n\nA5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care \\[(SOC) isoniazid\u002Frifampicin\u002Fpyrazinamide\u002Fethambutol (HRZE)\\].\n\nThe study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of study treatment (experimental or SOC, based on treatment arm assignment) followed by 18 weeks of SOC continuation phase treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm.",[576],"Pulmonary Tuberculosis",{"date":480,"type":41},{"date":579,"type":41},"2025-03-11",{"date":581,"type":22},"2027-08-11",{"name":47,"class":48},{"id":584,"slug":585,"hasResults":12,"nctId":586,"briefTitle":587,"officialTitle":588,"acronym":4,"eligibilityCriteria":589,"healthyVolunteers":12,"sex":17,"minAge":58,"maxAge":349,"enrollmentInfo":590,"targetDuration":4,"studyType":23,"phases":592,"briefSummary":593,"conditions":594,"keywords":4,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":535,"lastUpdatePostDateStruct":596,"startDateStruct":597,"completionDateStruct":599,"leadSponsor":601,"locationsCount":602},"100494535","phase-2-a-clinical-trial-of-combination-hiv-specific-broadly-neutralizing-monoclonal-antibodies-combined-with-art-initiation-during-acute-hiv-infection-to-induce-hiv-remission-100494535","NCT05719441","A Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission","A Double-Blind, Randomized, Placebo-Controlled Clinical Trial of Combination HIV-Specific Broadly Neutralizing Monoclonal Antibodies Combined With ART Initiation During Acute HIV Infection to Induce HIV Remission","Inclusion Criteria:\n\nStep 1:\n\n1. Appropriate documentation from medical records of diagnosis of AHI prior to enrollment that includes one of the following:\n\n   1. A detectable HIV-1 RNA within 28 days prior to study entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR\n   2. A detectable HIV-1 RNA or a reactive HIV-1 antibody within 28 days prior to study entry AND a negative\u002Findeterminate Western Blot (WB) or negative\u002Findeterminate Geenius HIV-1\u002FHIV-2 Supplemental Assay within 7 days prior to entry; OR\n   3. A documented non-reactive HIV-1 antibody or negative HIV-1 RNA within 90 days prior to study entry AND a documented reactive HIV-1 antibody or positive WB that is negative for p31 band or a positive Geenius HIV-1\u002FHIV-2 Supplemental Assay that is negative for p31 band within 7 days prior to entry; OR\n   4. ARCHITECT or GSCOMBO S\u002FCO ≥10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry; OR\n   5. ARCHITECT or GSCOMBO S\u002FCO ≥1 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND a known prior S\u002FCO \\\u003C0.5 within 90 days prior to entry; OR\n   6. ARCHITECT or GSCOMBO S\u002FCO \\>0.5 but \\\u003C10 within 7 days prior to entry AND a non-reactive HIV-1 antibody within 7 days prior to entry AND detectable HIV-1 RNA within 7 days prior to entry\n2. The following laboratory values obtained within 21 days prior to entry:\n\n   * Absolute neutrophil count (ANC) ˃1,000\u002Fmm3\n   * Hemoglobin:\n\n     * \\>10 g\u002FdL for cisgender men and transgender women\n     * \\>9 g\u002FdL for cisgender women and transgender men\n   * Platelet count ˃100,000\u002Fmm3\n   * Estimated glomerular filtration rate (eGFR) ≥50 mL\u002Fmin\u002F1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation, with consideration for lower rates in special circumstances.\n   * ALT (SGPT) ≤2.5 x ULN\n   * AST (SGOT) ≤2.5 x ULN\n   * Total bilirubin \\\u003C1.5 x ULN\n3. For persons who are able to become pregnant, negative urine or serum pregnancy test within 24 hours prior to study entry.\n4. Persons who are able to become pregnant must agree to use two methods of contraception throughout Step 1 if participating in sexual activity that could lead to pregnancy. One contraceptive method must be a highly effective method and the second method of contraception must be a barrier method.\n5. Participants of reproductive potential who engage in sexual activity that could lead to their partner's becoming pregnant must agree to use a barrier method of contraception throughout Step 1.\n6. Ability and willingness to use a barrier method or abstinence from sexual intercourse with all partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission during Step 2, Step 3, and until plasma HIV-1 RNA is less than the limit of detection after ART restart in Step 4.\n7. Age ≥18 and ≤70 years.\n8. Ability and willingness to initiate ART at enrollment.\n9. Ability and willingness to participate in scheduled study visits, including during the ATI, per Schedule of Evaluations (SOE).\n10. Ability and willingness of participant to provide informed consent.\n\nStep 2:\n\n1. Documented negative hepatitis B virus (HBV) surface antigen (HBsAg) obtained within 16 weeks prior to Step 2 registration.\n2. Documented negative hepatitis C virus (HCV) antibody (anti-HCV) or negative HCV RNA PCR obtained within 16 weeks prior to Step 2 registration.\n3. Receipt of full doses of study infusions at enrollment (VRC07-523LS + PGT121.414.LS or placebo \\[Sodium Chloride for Injection USP, 0.9%\\]).\n4. HIV-1 RNA \\\u003C200 copies\u002FmL obtained within 6 weeks prior to Step 2 registration.\n5. CD4+ T-cell count ≥450 cells\u002Fmm3 obtained within 6 weeks prior to Step 2 registration.\n6. For participants who are able to become pregnant, negative serum or urine pregnancy test within 48 hours prior to Step 2 entry.\n7. To avoid pregnancy, participants who are able to become pregnant must agree to use contraception or practice abstinence from sexual activity that could lead to pregnancy throughout Step 2.\n8. Ability and willingness to use a barrier method or abstinence from sexual intercourse with partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission throughout Step 2.\n9. Ability and willingness to interrupt ART.\n10. Completion of Step 1.\n\nStep 3:\n\n1. Has not met ART restart criteria.\n2. Completion of Step 2.\n3. Willing to continue ATI.\n4. To avoid pregnancy, participants who are able to become pregnant must agree to use contraception or practice abstinence from sexual activity that could lead to pregnancy throughout Step 3.\n5. Ability and willingness to use a barrier method or abstinence from sexual intercourse with all partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission throughout Step 3.\n\nStep 4:\n\n1. Has met any of the ART restart criteria during Step 2 or Step 3. -OR- Has completed Step 3 and is not enrolling to ACTG A5385.\n2. To avoid pregnancy, participants who are able to become pregnant must agree to use contraception or practice abstinence from sexual activity that could lead to pregnancy throughout Step 4.\n3. Ability and willingness to use a barrier method or abstinence from sexual intercourse with all partners who are vulnerable to HIV or whose HIV serostatus is unknown in order to prevent HIV transmission until plasma HIV-1 RNA is less than the limit of detection after ART restart.\n\nExclusion Criteria:\n\nStep 1:\n\n1. Previous receipt of immunoglobulin (IgG) therapy.\n2. Previous receipt of humanized or human monoclonal antibody whether licensed or investigational (other than for the prevention and\u002For treatment of SARS-CoV-2\u002FCOVID-19).\n3. History of a severe allergic reaction with generalized urticaria, angioedema or anaphylaxis in the 2 years prior to enrollment.\n4. History of chronic urticaria requiring daily treatment.\n5. Receipt of investigational study agent within 28 days prior to enrollment.\n6. Past participation in an investigational study of a candidate HIV vaccine or immune prophylaxis for HIV-1 infection with receipt of active product or with receipt of active product or placebo and remains blinded to what they actually received.\n7. Active or recent non-HIV-associated malignancy requiring systemic chemotherapy or surgery in the preceding 36 months or for whom such therapies are expected in the subsequent 12 months.\n8. Use of any immunomodulatory medications within 6 months of study entry including systemic corticosteroids (long-term), immunosuppressants, anti-cancer, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immune modulatory effect.\n9. Use of ART for any reason, including pre- or post-exposure prophylaxis, within 60 days prior to study entry.\n10. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.\n11. Known history of active Hepatitis B or Hepatitis C infection.\n12. Any acute, chronic, or recent and clinically significant medical condition that, in the opinion of the site investigator, would interfere with adherence to study requirements or jeopardize the safety or rights of the participant.\n13. History of or current clinical atherosclerotic cardiovascular disease (ASCVD) as defined by 2013 American College of Cardiology (ACC)\u002FAmerican Heart Association (AHA) guidelines, including a previous diagnosis of any of the following:\n\n    * Acute myocardial infarction\n    * Acute coronary syndromes\n    * Stable or unstable angina\n    * Coronary or other arterial revascularization\n    * Stroke\n    * TIA\n    * Peripheral arterial disease presumed to be of atherosclerotic origin\n14. Currently breastfeeding or pregnant.\n15. Weight \\>115 kg.\n16. Use of prohibited medications for bictegravir, emtricitabine, and tenofovir alafenamide (refer to protocol section 5.8) within 7 days prior to entry, or planned use of prohibited medications during the period of study participation.\n17. Absence of adequate venous access for the administration of infusion or for phlebotomy to assess for the primary study endpoint.\n\nStep 2:\n\n1. Viral failure, as defined in protocol section 6.2.4, after Step 1 week 24.\n2. Failure to initiate ART in Step 1.\n3. Receipt of any non-nucleoside reverse transcriptase inhibitor (NNRTI) or long-acting ART (any therapy dosed at an interval less than daily), such as cabotegravir or rilpivirine injections, after Step 1 entry.\n4. Receipt of any immunoglobulin therapy or immunomodulatory medications after Step 1 entry including systemic corticosteroids (long-term), immunosuppressants, anti-cancer, interleukins, systemic interferons, systemic chemotherapy, or other medications that the site investigator feels could have an immune modulatory effect.\n5. Does not have HIV-1.\n6. Participant was in Fiebig stage VI at the time of study entry.\n7. Failure by the participant to attend three consecutive Step 1 study visits.\n8. Intercurrent illness, new medical diagnosis, laboratory abnormality, sign, or symptom that, in the opinion of the site investigator, would place participant at higher risk of morbidity during ATI.\n9. Pregnancy or breastfeeding.\n10. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.\n\nStep 3:\n\n1. Transfer to A5385 (The Post-Intervention Cohort Study).\n2. ART restart in Step 2.\n3. Intercurrent illness, new medical diagnosis, laboratory abnormality, sign, or symptom that, in the opinion of the site investigator, would place participant at higher risk of morbidity during analytic treatment interruption.\n4. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.\n\nStep 4:\n\n1\\. Unwillingness or inability to restart ART after meeting an ART restart criterion in Step 2 or Step 3.",{"count":591,"type":22},48,[26],"A5388 is a phase II, two-arm, randomized, double-blind, placebo-controlled study that will enroll 48 antiretroviral therapy (ART)-naïve adults with acute HIV infection (AHI) in order to determine whether:\n\n* Administration of combination HIV-specific broadly neutralizing antibody (bNAb) therapy in addition to ART during acute HIV infection (AHI) will be safe.\n* Participants who receive combination bNAb therapy in addition to ART during AHI will be more likely to demonstrate a delay in time to HIV-1 RNA ≥1,000 copies\u002FmL for 4 consecutive weeks compared to participants who receive placebo plus ART.\n* Participants who receive combination bNAb therapy in addition to ART during AHI will demonstrate lower viral reservoirs and enhanced HIV-specific immunity compared to participants who receive placebo plus ART.",[595],"Acute HIV Infection",{"date":480,"type":41},{"date":598,"type":41},"2024-08-19",{"date":600,"type":22},"2028-09-06",{"name":47,"class":48},36,{"id":604,"slug":605,"hasResults":12,"nctId":606,"briefTitle":607,"officialTitle":608,"acronym":4,"eligibilityCriteria":609,"healthyVolunteers":12,"sex":17,"minAge":4,"maxAge":610,"enrollmentInfo":611,"targetDuration":4,"studyType":23,"phases":613,"briefSummary":614,"conditions":615,"keywords":616,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":535,"lastUpdatePostDateStruct":618,"startDateStruct":619,"completionDateStruct":621,"leadSponsor":623,"locationsCount":624},"100219916","phase-1-very-early-intensive-treatment-of-infants-living-with-hiv-to-achieve-hiv-remission-100219916","NCT02140255","Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission","Very Early Intensive Treatment of Infants Living With HIV to Achieve HIV Remission: A Phase I\u002FII Proof of Concept Study","Maternal Inclusion Criteria\n\n1. Presumed or confirmed maternal HIV infection:\n\n   * Mothers will be eligible to enroll with EITHER:\n\n     * Presumed HIV infection defined as at least one positive rapid HIV antibody-based test result from a sample collected in the peripartum period. Presumed infection must be confirmed within 10 business days of enrollment OR\n     * Confirmed HIV infection defined as positive results from two samples collected at different timepoints\n2. Willing and able to provide written informed consent for participation of herself and her infant. The mother must be of legal age or circumstance to provide independent informed consent as determined by site standard operating procedures (SOPs) and consistent with IRB\u002FEC policies and procedures. Otherwise, informed consent must be obtained from a legal guardian and the mother must provide written assent.\n3. Was not previously enrolled in this study with another infant.\n4. Did not receive ARVs during the current pregnancy.\n5. Infant is eligible per inclusion criteria.\n\nInfant Inclusion Criteria for Step 1\n\n1. Less than or equal to 48 hours of age.\n2. Greater than or equal to 37 weeks gestational age at birth (assessment of gestational age will be based on the best clinical estimate determined by date of last menstrual period, antenatal ultrasound, fundal height, or Ballard Score).\n3. Greater than or equal to 2 kilograms (kg) at birth.\n4. Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube.\n5. Has no clinically significant diseases (other than HIV infection) or clinically significant findings during review of medical history or physical examination prior to entry that, in the site investigator's opinion, would interfere with study participation or interpretation.\n6. Mother is eligible per inclusion criteria.\n\nInfant Inclusion Criteria for Step 2\n\n1. Enrolled in Step 1.\n2. Confirmed in utero HIV infection.\n3. Able to take ARVs by mouth, nasogastric tube, or gastrostomy tube.\n4. Has no clinically significant diseases (other than HIV infection) or clinically significant findings during review of medical history or physical examination prior to entry that, in the site investigator's opinion, would interfere with study participation or interpretation.\n5. Mother (or legal guardian if applicable) is willing and able to provide written informed consent for child's participation in Step 2.\n\nInfant Inclusion Criteria for Step 3\n\n1. Enrolled in Step 2.\n2. Has reached Step 2 Week 96.\n3. Has the following results based on testing:\n\n   * No confirmed plasma HIV RNA ≥200 copies\u002FmL at Step 2 Week 24 and up to but excluding Step 2 Week 48.\n   * No plasma HIV RNA detected at Step 2 Week 48 and thereafter, with two possible exceptions\n\n     * (i) First possible exception: If HIV RNA is detected at or after Step 2 Week 48 with a result \\\u003C200 copies\u002FmL, testing will be repeated within three weeks (specimen collection for the confirmatory test must occur within three weeks of specimen collection for the initial test).\n     * If no HIV RNA is detected on the confirmatory test, or if HIV RNA is detected with a result \\\u003C200 copies\u002FmL, the infant will be potentially eligible for Step 3 after an additional 48 weeks of follow-up in Step 2, provided no HIV RNA is detected on any subsequent tests in Step 2.\n     * If HIV RNA is detected on the confirmatory test with a result ≥200 copies\u002FmL, the infant will not be eligible for Step 3.\n     * (ii) Second possible exception: If HIV RNA is detected after Step 2 Week 48 with a result \\\u003CLOD, the infant will be potentially eligible for Step 3 after an additional 48 weeks of follow-up in Step 2 with no RNA detected. There is no limit on the number of times HIV RNA may be detected with a result \\\u003CLOD after Week 48. However, infants with detectable RNA with a result \\\u003CLOD after Week 48 will not be considered for entry into Step 3 until after an additional 48 weeks of no RNA detected.\n     * Participants may experience either or both exceptions at different timepoints during follow-up in Step 2.\n4. If breastfed, must have permanently ceased breastfeeding, with no exposure to breast milk for at least six weeks prior to specimen collection for the testing specified in the criterion (#5) below.\n5. Has met ALL of the following additional criteria while in Step 2, based on testing between Step 2 Week 84 and Step 2 Week 192 (inclusive):\n\n   * Two consecutive negative HIV antibody tests by fourth generation ELISA at least eight weeks apart.\n   * Two consecutive HIV DNA tests with no DNA detected in at least 850,000 PBMCs assayed at least eight weeks apart.\n   * CD4 cell percentage greater than or equal to 25% and CD4 cell absolute count greater than or equal to the lower limit of normal for age (≥1000 cells\u002FmL if 2 to less than 3 years of age; ≥750 cells\u002FmL if 3 to less than 5 years of age; ≥500 cells\u002FmL if 5 years of age or older).\n   * Infant assessed by the site investigator or designee as expected to adhere to the Step 3 Schedule of Evaluations.\n   * Mother (or legal guardian if applicable) willing and able to provide written informed consent for child's participation in Step 3 and Step 4.\n6. No plasma HIV RNA detected by testing after criteria have been confirmed, with specimen collection for the assay within 14 days prior to Step 3 Entry.\n\nInfant Inclusion Criteria for Step 4\n\n1. Enrolled in Step 3.\n2. Has met at least one of the following:\n\n   * Plasma HIV RNA ≥LOD based on two assays.\n   * Plasma HIV RNA ≥1000 copies\u002FmL in the presence of fever or other sign or symptom of acute retroviral syndrome.\n   * Confirmed or suspected diagnosis of acute retroviral syndrome.\n   * Confirmed or suspected diagnosis of a new WHO Clinical Stage 3 or 4 condition.\n   * Confirmed CD4 cell percentage less than 25% and CD4 cell absolute count less than the lower limit of normal for age (\\\u003C1000 cells\u002FmL if 2 to less than 3 years of age; \\\u003C750 cells\u002FmL if 3 to less than 5 years of age; \\\u003C500 cells\u002FmL if 5 years of age or older).\n   * Otherwise assessed by the site investigator or designee, in consultation with the Clinical Management Committee (CMC), as having an indication to re-initiate treatment.","48 Hours",{"count":612,"type":22},1120,[25,26],"The study will explore the effects of early intensive antiretroviral therapy (ART) with or without a broadly neutralizing antibody (bNAb) on achieving HIV remission (HIV RNA below the limit of detection of the assay) among infants living with HIV.",[376],[617],"HIV Remission",{"date":381,"type":41},{"date":620,"type":41},"2015-01-23",{"date":622,"type":22},"2031-12-31",{"name":47,"class":48},46,{"id":626,"slug":627,"hasResults":12,"nctId":628,"briefTitle":629,"officialTitle":630,"acronym":4,"eligibilityCriteria":631,"healthyVolunteers":12,"sex":17,"minAge":279,"maxAge":19,"enrollmentInfo":632,"targetDuration":4,"studyType":23,"phases":633,"briefSummary":634,"conditions":635,"keywords":637,"overallStatus":113,"whyStopped":4,"lastUpdateSubmitDate":144,"lastUpdatePostDateStruct":639,"startDateStruct":640,"completionDateStruct":642,"leadSponsor":644,"locationsCount":49},"100608518","randomized-stepped-wedge-study-of-emapalumab-in-apeced-enteritis-100608518","NCT07202598","Randomized Stepped Wedge Study of Emapalumab in APECED Enteritis","A Phase 2 Randomized Stepped Wedge Study of Emapalumab in APECED Enteritis","* INCLUSION CRITERIA:\n\n  1. Participant must be able to understand and provide informed consent.\n  2. Aged \\>= 2 to \\\u003C= 75 years.\n  3. Currently co-enrolled on NIH protocol 11-I-0187, \"The Natural History and Pathogenesis of Human Fungal Infections.\"\n  4. Patients with APECED (genetic or clinical diagnosis) and enteritis (with APECED ES \\> 50 at screening).\n  5. Duration of enteritis greater than 6 months.\n  6. Is naive or unresponsive to other treatments for enteritis.\n  7. Willingness to use acyclovir or valacyclovir prophylaxis for the prevention of herpes viral reactivation.\n  8. Willingness to use entecavir prophylaxis against hepatitis B virus reactivation, if applicable.\n  9. Vaccinations should be up to date in agreement with current Centers for Disease Control and Prevention immunization guidelines prior to start of emapalumab.\n  10. Proficient in written English.\n  11. Participants who can get pregnant or impregnate their partner must agree to use at least one highly effective method of contraception when engaging in sexual activities that can result in pregnancy, starting at screening until 12 weeks after the last dose. Highly effective contraceptive measures include:\n* Stable use of combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) starting 1 month prior to screening.\n* Intrauterine device (IUD); intrauterine hormone-releasing system.\n* Two barrier methods (e.g., condom with spermicide, diaphragm with spermicide, or cervical cap and spermicide). Internal and external condoms may not be used together.\n* Bilateral tubal ligation.\n\nPeriodic abstinence (calendar, symptothermal, and post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.\n\nEXCLUSION CRITERIA:\n\n1. Known history of hypersensitivity to emapalumab.\n2. History of active intestinal disease other than enteritis such as inflammatory bowel disease.\n3. Current or recent use of any investigational drug (within 3 months or 5 half-lives, whichever is longer, prior to screening).\n4. Scheduled to participate in another clinical study involving an investigational drug during the course of this study.\n5. History of alcohol or drug abuse within 6 months prior to screening.\n6. Presence of one or more of the following clinically significant laboratory abnormalities:\n\n   1. Serum ALT \\>= 3 times upper limit of normal (ULN).\n   2. Serum total bilirubin \\>= 2 times ULN.\n   3. Serum creatinine \\>= 2 times ULN.\n7. Planned or anticipated major surgical procedure during the study.\n8. Plans to receive any live or live attenuated vaccines within 1 month of the anticipated first dose of emapalumab.\n9. Known or suspected immunodeficiency disorder besides APECED.\n10. History of untreated invasive opportunistic infections (e.g., tuberculosis, non-tuberculous mycobacterial infections, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis pneumonia, aspergillosis) despite infection resolution or otherwise recurrent infections of abnormal frequency or prolonged infections suggesting an immune-compromised status as judged by the investigator.\n11. Untreated latent tuberculosis infection.\n12. Infection with HIV.\n13. Untreated infection with hepatitis B or C.\n14. History of serious bacterial infection within the last 3 months prior to screening, unless treated and resolved with antibiotics, or any chronic bacterial infection (e.g., chronic pyelonephritis, osteomyelitis).\n15. Current pregnancy or breastfeeding.\n16. Past or current medical problems or findings from physical examination, EKG, or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.",{"count":470,"type":22},[26],"Background:\n\nAutoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also known as Autoimmune polyendocrine syndrome type-1 (APS-1), is a disease that causes the immune system to attack parts of a person's body. In some people, APECED attacks the small intestine; this causes an illness called enteritis.\n\nObjective:\n\nTo test a drug (emapalumab) in people with enteritis caused by APECED.\n\nEligibility:\n\nPeople aged 2 to 75 years with APECED and enteritis. They must also be enrolled in protocol 11-I-0187.\n\nDesign:\n\nParticipants will have 10-13 study visits in an 18-month period.\n\nParticipants will be screened. They will have a physical exam with blood tests. These tests will be repeated at every study visit. They will have a test of their heart function. This will be at screening and prior to drug administration.\n\nOther tests are optional: Participants may have imaging exams and a test of lung function. They may have an endoscopy, which is an exam of their digestive tract. Participants may provide samples of urine, stool, nail clippings, saliva, vaginal fluid, or skin. Photos may be taken of their skin or scalp. These tests may be repeated at some visits.\n\nEmapalumab is given through a tube attached to a needle inserted into a vein. All participants will receive 7 doses: 2 on their first study visit; then 1 each at 30-day intervals. Some participants will have an observation period before they begin taking the drug; in those situations, they will either be seen in person or via video visit every 2 months before starting emapalumab to see how their symptoms change over time.\n\nParticipants will have a follow-up visit 1 month after their last dose. Then they will have 2 telehealth visits at 30-day intervals. They will have a final clinic visit 1 year after their first dose.\n\n...",[636],"Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy Enteritis",[638],"Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy",{"date":480,"type":41},{"date":641,"type":41},"2025-11-12",{"date":643,"type":22},"2031-09-01",{"name":47,"class":48},""]