[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"TASK Applied Science\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":78},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,45],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":29,"overallStatus":32,"whyStopped":4,"lastUpdateSubmitDate":33,"lastUpdatePostDateStruct":34,"startDateStruct":37,"completionDateStruct":39,"leadSponsor":41,"locationsCount":44},"100652539","phase-2-study-of-combinations-of-novel-promising-drugs-for-pulmonary-tuberculosis-100652539",false,"NCT07773610","Study of Combinations of Novel Promising Drugs for Pulmonary Tuberculosis","A Phase 2, Randomised, Controlled, Multicentre Two-Part Trial Assessing the Safety and Efficacy of TBAJ-587 as Part of a Combination Regimen in Newly Diagnosed, Drug-Sensitive, Sputum-Positive Pulmonary Tuberculosis","SYNERGY","Inclusion Criteria:\n\n* To be eligible to participate in this trial, an individual must meet all the following criteria:\n\n  1. Provide written informed consent.\n  2. Male or female aged 18-65 (inclusive)\n  3. Clinical evidence of active TB disease, meeting either or both of the following criteria:\n\n     1. Symptoms consistent with pulmonary TB at screening AND\u002FOR\n     2. Imaging findings consistent with active pulmonary TB on chest X-ray performed at screening or within 15 days prior to screening.\n  4. At least one sputum specimen produced at screening tested on either of the following:\n\n     Xpert MTB\u002FXDR and Ultra with:\n     * positive for M. tb\n     * a semi-quantitative result of 'medium' (cycle threshold value of \\>16-22) or 'high' (cycle threshold value of \\>16-22) AND\n     * does not show rifampicin and\u002For isoniazid resistance. OR\n\n       a. Sputum smear\n     * Sputum positive for tubercle bacilli (at least 1+ on the IUATLD\u002FWHO scale on smear microscopy) AND o Sensitive to rifampicin and isoniazid by rapid sputum-based test.\n  5. Able to produce a spot sputum with a volume of at least 4 ml.\n  6. Body weight within the range of 30 to 100 kgs and body mass index within the range of 15 to 40 kg\u002Fm2.\n  7. Newly diagnosed and untreated for this episode of TB.\n  8. Individuals with a history of TB may be enrolled in this trial if they meet the following criteria:\n\n     1. had a good treatment response in the opinion of the investigator (previous TB symptoms improved sufficiently or resolved) AND\n     2. completed their previous TB treatment AND\n     3. received their last dose of treatment more than 6 months before trial treatment AND • remained clinically well after completing treatment for their previous TB.\n  9. Willing to abstain from alcohol and tyramine containing foods for the treatment duration.\n  10. Willing to comply with study visits, all study procedures and treatment observation.\n\nExclusion Criteria:\n\n* An individual who meets any of the following criteria will be excluded from participation in this trial:\n\n  1. Taken more than 1 daily dose of medication with anti-tuberculous activity during the 14 days prior to randomisation (isoniazid, rifampicin, pyrazinamide, ethambutol, linezolid, moxifloxacin, levofloxacin or amikacin).\n  2. Known or suspected extra-thoracic TB, miliary TB or disseminated TB (in the judgement of the investigator; note uncomplicated pleural effusion occupying \\\u003C50% of hemithorax or concomitant intra- or extra-thoracic lymphadenopathy are not exclusions).\n  3. Severe clinical pulmonary TB e.g. respiratory failure or complications, likely to require hospital admission in the opinion of the investigator.\n  4. Poor general condition (Karnofsky score ≤50) OR where any delay in treatment cannot be tolerated in the opinion of the investigator.\n  5. Active malignancy requiring systemic therapy, radiotherapy or palliative therapy.\n  6. History of myocardial infarction, coronary heart disease or congestive cardiac failure; long QT syndrome or clinically significant arrhythmias; pulmonary hypertension; any known congenital cardiac problems; family history of long QT syndrome or sudden death from unknown or cardiac related cause; uncontrolled arterial hypertension (not excluded if this is corrected prior to randomisation).\n  7. Cardiac valve abnormalities identified on echocardiogram.\n  8. History of vitiligo.\n  9. History of, or ongoing, inflammatory skin disorder such as leprosy, eczema, psoriasis, lichen planus, or other skin rash that would, in the opinion of the investigator, compromise the participant's safety or outcome in the trial.\n  10. History of seizure(s).\n  11. History of vascular aneurysm.\n  12. Symptomatic peripheral neuropathy causing greater than minimal interference with usual social and functional activities.\n  13. History of optic neuritis.\n  14. Current alcohol or illicit drug use sufficient to compromise the safety of the participant or research staff or compromise adherence to study procedures, in the opinion of the investigator.\n  15. Any current or recent use of amphetamines or methamphetamines evident on toxicity screen.\n  16. Any other medically or socially significant condition (e.g. psychiatric illness, chronic diarrhoeal disease, metabolic condition, other cardiovascular disease not listed under criterion 6), that would, in the opinion of the investigator, compromise the participant's safety or outcome in the trial; or lead to poor compliance with study visits and protocol requirements; or compromise the interpretation of trial safety and efficacy endpoints.\n  17. Women who are currently pregnant or breast-feeding.\n  18. Women of childbearing potential (WOCBP) who have had sexual intercourse without contraception after last menses or within the last 3 weeks (whichever is later); or, if unwilling to disclose this information, unable to provide two negative pregnancy tests 8 days apart during the screening period and on day 1 prior to randomisation .\n  19. WOCBP unwilling or unable to use appropriate non-user dependent contraception during the study intervention period and for at least 6 months after the last dose of study intervention; and unwilling to commit to refrain from donating eggs (ova, oocytes) for the purpose of reproduction during this period\n  20. Men who are unwilling to use a condom during the study period and for at least 90 days after the last dose of study drug to prevent pregnancy, unless they have had a vasectomy; and are unwilling to commit to refrain from donating fresh unwashed semen.\n  21. Known allergy to one or more of the study drugs.\n  22. Taking a concomitant medication that has a known or predicted interaction with any of the study drugs to which the participant might be randomised\n\n      The participant need not be excluded if:\n      1. the concomitant medication can be stopped or replaced with an alternative non-interacting medication, if needed AND\n      2. the investigator judges there to be no residual clinical risk to the participant after stopping the concomitant medication (taking into account the washout period of 5x the half-life of the concomitant medication and the duration of the effect of the interaction on levels of study medication).\n  23. Taking a concomitant medication that is known to prolong the QTc interval. The participant need not be excluded if the concomitant medication can be stopped or replaced with an alternative medication, if needed, and the duration of the QTc prolongation is expected to resolve prior to dosing of study medication (taking into account the washout period of 5x the half-life of the concomitant medication).\n  24. Treatment with any immunosuppressive drugs within the 2 weeks prior to screening (taking systemic corticosteroids for less than 5 consecutive days and stopped at or prior to screening is not an exclusion; topical or inhaled steroids that are taken at a dose below the threshold considered to have systemic immunosuppressive effects are not excluded).\n  25. Participation in other clinical intervention trials with an investigational agent within 8 weeks prior to the first dosing day in this trial.\n  26. 12-lead ECGs at screening or at baseline shows QTcF \\>450 ms (men) or \\>460 ms (women) calculated by Fridericia's formula; and\u002For any other clinically significant abnormality such as arrhythmia or ischaemia.\n  27. Any of the following laboratory parameters at screening:\n\n      1. Hemoglobin \\\u003C 9 g\u002Fdl\n      2. Platelet count \\\u003C 100 x 109 cells\u002FL\n      3. Absolute neutrophil count \\\u003C1 000 cells\u002FμL\n      4. eGFR \\\u003C75 ml\u002Fmin, calculated using race free CKD EPI 2021 eGFR normalised by body surface area through additional inclusion of weight AND height parameters (not excluded if corrected to above this level)\n      5. Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \\> 3 times the upper limit of normal (ULN)\n      6. Total bilirubin \\> 1.5 times the ULN\n      7. Serum potassium \\\u003C3.5 mmol\u002FL (not excluded if corrected to above this level)\n      8. Serum magnesium \\\u003C 0.50mmol\u002FL (not excluded if corrected to above this level)\n      9. Serum calcium (corrected for albumin level) \\\u003C 2.10 mmol\u002FL (not excluded if corrected to above this level).\n      10. HbA1C \\>8.0%\n  28. Hepatitis B surface antigen positive (known, or on a test performed at screening), hepatitis A IgM and hepatitis C antibodies. (Participants with positive hepatitis C antibodies but negative PCR can be allowed in the trial)\n  29. Human Immunodeficiency Virus (HIV) antibody positive (known, or on test performed at screening) unless ALL of the following conditions are met:\n\n      1. Viral load (HIV-RNA) below 200 copies\u002FmL on the last test, done within the previous 90 days (or at screening if no test performed in the previous 90 days).\n      2. CD4 count \\> 200 cells\u002Fmm3 on the last test, done within the previous 90 days (or at screening if no test performed in the previous 90 days).\n      3. The participant has been taking a regimen of dolutegravir (DTG), tenofovir (TFV) and lamivudine(3TC)\u002Femtricitabine for at least 6 months prior to screening with good adherence.\n  30. For Part B only: Participants unwilling or unable to disclose information regarding their last unprotected sexual intercourse (UPSI), or whose responses are considered unreliable or non-compliant by the Investigator.","ALL","18 Years","65 Years",{"count":21,"type":22},135,"ESTIMATED","INTERVENTIONAL",[25],"PHASE2","A phase 2, two-part, multicentre, open label, controlled, randomised clinical trial in adult participants with newly diagnosed, sputum-positive pulmonary drug-sensitive tuberculosis (DSTB). Assessing the Safety and Efficacy of TBAJ-587 as Part of a Combination Regimen in Newly Diagnosed, Drug-Sensitive, Sputum-Positive Pulmonary Tuberculosis",[28],"Tuberculosis, Pulmonary",[30,31],"Drug-Sensitive Tuberculosis","Sputum-Positive Tuberculosis","NOT_YET_RECRUITING","2026-08-14",{"date":35,"type":36},"2026-08-19","ACTUAL",{"date":38,"type":22},"2026-07-23",{"date":40,"type":22},"2027-12-30",{"name":42,"class":43},"TASK Applied Science","OTHER",1,{"id":46,"slug":47,"hasResults":11,"nctId":48,"briefTitle":49,"officialTitle":50,"acronym":51,"eligibilityCriteria":52,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":53,"targetDuration":4,"studyType":23,"phases":55,"briefSummary":56,"conditions":57,"keywords":59,"overallStatus":69,"whyStopped":4,"lastUpdateSubmitDate":70,"lastUpdatePostDateStruct":71,"startDateStruct":73,"completionDateStruct":75,"leadSponsor":77,"locationsCount":44},"100573642","phase-2-a-study-of-the-early-effects-safety-and-acceptability-of-oral-alpibectir-in-combination-with-ethionamide-100573642","NCT06748937","A Study of the Early Effects, Safety, and Acceptability of Oral Alpibectir in Combination With Ethionamide","A Phase 2 Randomized, Open-label Trial to Evaluate the Early Bactericidal Activity, Safety, Tolerability, and Dose-Response of Oral Alpibectir in Combination With Ethionamide, and With Ethionamide, Rifampicin, Pyrazinamide, and Ethambutol in Adults With Newly Diagnosed, Drug-Susceptible Pulmonary Tuberculosis","ENABLE","Inclusion Criteria:\n\n1. Provide written, informed consent prior to all trial-related procedures and willing to adhere to all required study procedures and restrictions for the duration of the trial.\n2. Male or female, aged between 18 and 65 years, inclusive.\n3. Body weight (in light clothing and with no shoes) between 40 and 90 kg, inclusive.\n4. Newly diagnosed and untreated for this episode of pulmonary TB.\n5. Rifampicin- and isoniazid susceptible pulmonary TB as determined by molecular testing (GeneXpert XDR or Genotype MTBDRplus for INH).\n6. A chest X-ray taken during the screening period or up to 2 weeks before screening which, in the opinion of the investigator, is consistent with TB.\n7. GeneXpert positive with a quantitative readout of medium or high.\n8. Ability to produce an adequate volume of sputum as estimated from an overnight sputum collection sample (estimated 10 ml or more).\n9. Be of non-childbearing potential or of childbearing potential using effective methods of birth control, as defined in section 5.2 and in Appendix 1.\n\n   Female Participants\n10. For WOCBP who are not already receiving contraception per Appendix 1 requirements, agree to receive injectable or other contraceptive methods (per Appendix 1), to be given during screening, and at least 1 day prior to first dose of IMP.\n\n    Male Participants\n11. Agree to ALL of the following during the study intervention period and for at least 90 days, after the last dose of study intervention:\n\n    1. Refrain from donating fresh unwashed semen\n    2. Agree to use a male condom when engaging in any activity that allows for passage of ejaculate to another person.\n\nExclusion Criteria:\n\n1. Evidence of clinically significant conditions or findings, other than TB, that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.\n2. Poor general condition where any delay in treatment cannot be tolerated per discretion of the investigator.\n3. History of epilepsy, seizures or other neuropsychiatric disorders that might compromise safety or the interpretation of trial endpoints, per discretion of the investigator.\n4. Cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, persistent jaundice (with the exception of Gilbert's syndrome or asymptomatic gallstones).\n5. History of hypothyroidism\n6. QTcF of \\>450 ms at baseline\n7. Clinically significant evidence of extra-thoracic TB, as judged by the investigator.\n8. History of allergy to any of the trial IMP as confirmed by the clinical judgement of the investigator.\n9. Alcohol or drug abuse, that in the opinion of the investigator, is sufficient to compromise the safety or cooperation of the participant.\n10. HIV positive AND:\n\n    1. CD4 \\\u003C 250cells\u002Fmm3\n    2. On other ART regimen not listed below or, if not on ART they are not willing to wait to start treatment until completion of study regimen\n\n    Note: ART regimens permitted is limited to the following in line with local guidelines for 1st line ART:\n    * NRTIs selected from: Emtricitabine, Lamivudine, Tenofovir\n    * PLUS Dolutegravir 50 mg daily, or 50 mg twice daily if randomized to a rifampicin containing arm.\n\n    Participants established on ART (2 NRTIs and dolutegravir) for more than 30 days at start of screening are eligible for participation.\n\n    As the drug-drug interaction potential of ART has not been fully investigated with the IMP, NNRTIs (efavirenz, nevirapine) and other protease inhibitors will not be permitted in this study.\n11. Female participant who is pregnant, breast-feeding, or planning to conceive a child within the anticipated period of trial participation and for at least 90 days after the last dose of study intervention. Male participant planning to conceive a child for at least 90 days, after the last dose of study intervention in the trial.\n\n    Treatment History\n12. Participation in other clinical studies with investigational agents within 8 weeks prior to screening.\n13. Treatment received for this episode of TB with any drug active against M. tb (including but not limited to isoniazid, ethambutol, cycloserine, fluoroquinolones, rifamycins, aminoglycosides, nitroimidazoles, bedaquiline, oxazolidinones, para-amino salicylic acid, pyrazinamide, thioacetazone, thioamides).\n14. Treatment with immunosuppressive medications such as TNF-alpha inhibitors within 2 weeks prior to screening, or systemic corticosteroids for more than 7 days within 2 weeks prior to screening.\n15. Unavoidable treatment with prohibited concomitant medications (see section 5.3.2) anticipated during administration of IMP.\n\n    Laboratory Safety Testing\n16. Presence of hepatitis B surface antigen (HBsAg+)\n17. Positive hepatitis C antibody test result (HCV IgG+)\n18. Participants with the following toxicities at screening as defined by the enhanced CTCAE toxicity table:\n\n    1. creatinine \\>1.5 times upper limit of normal (ULN)\n    2. haemoglobin \\\u003C8.0 g\u002FdL\n    3. platelets \\\u003C50x109 cells\u002FL\n    4. serum potassium \\\u003C3.0 mmol\u002FL\n    5. alanine aminotransferase (ALT) ≥5 x ULN\n    6. total bilirubin \\>1.5 x ULN; Participants with Gilbert's syndrome can be included with total bilirubin \\>1.5 x ULN as long as direct bilirubin is ≤1.5xULN\n    7. Total white cell count \\\u003C1.5 cells\u002FL\n    8. Thyroid Stimulating Hormone \\> ULN\n    9. Glucose \\\u003C 3.5 mmol\u002FL",{"count":54,"type":22},60,[25],"A multi-centre, randomized, open-label clinical trial. All treatments will be administered orally (PO) on days 1-14.\n\n15 participants will be recruited into each treatment arm in two sequential cohorts. Each cohort will have participants enrolled onto the experimental regimen(s) or the standard of care (SOC; HRZE) control arm.\n\n• Cohort 1 aims to generate safety data for a higher dose of alpibectir plus ethionamide 125 mg and 250 mg (arm 1: A45E125 and arm2: A45E250).\n\nOnce 5 participants have enrolled into arms 1 and 2 each, and completed 14 days of treatment, an interim safety review will be conducted to determine whether the study can advance to cohort 2.\n\n• Cohort 2 will investigate safety of alpibectir and ethionamide (A45E250) in combination with rifampicin, pyrazinamide and ethambutol (A45E250RZE).\n\nParticipants on HRZE will serve as control for the EBA quantitative mycobacteriology in each cohort, and additionally as a safety benchmark for the A45E250RZE arm. The study is not statistically powered to make between arm comparisons of activity or safety. The treatment will not be blinded but the mycobacteriology laboratory staff performing the endpoint assays will remain blinded until analysis of the EBA results.",[58],"Tuberculosis",[60,61,62,63,64,65,66,67,68],"Alpibectir","Ethionamide","Rifampicin","Pyrazinamide","Ethambutol","Adults","Newly Diagnosed","Drug- Susceptible","Pulmonary Tuberculosis","RECRUITING","2025-03-04",{"date":72,"type":36},"2025-03-07",{"date":74,"type":36},"2025-03-03",{"date":76,"type":22},"2026-03-30",{"name":42,"class":43},""]