[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100659377":3},{"organization":4,"outcomesModule":7,"designInfo":47,"detailedDescription":59,"studyPopulation":46,"armGroups":60,"interventions":74,"overallOfficials":91,"centralContacts":95,"locations":101,"responsibleParty":118,"collaborators":120,"id":131,"slug":132,"hasResults":133,"nctId":134,"briefTitle":135,"officialTitle":136,"acronym":137,"eligibilityCriteria":138,"healthyVolunteers":139,"sex":140,"minAge":141,"maxAge":142,"enrollmentInfo":143,"targetDuration":46,"studyType":146,"phases":147,"briefSummary":149,"conditions":150,"keywords":152,"overallStatus":160,"whyStopped":46,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":165,"completionDateStruct":167,"leadSponsor":169,"locationsCount":170},{"fullName":5,"class":6},"Murdoch Childrens Research Institute","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":46},[9],{"measure":10,"description":11,"timeFrame":12},"Acute symptomatic pharyngitis (disease) - proportion of participants in each arm who reach the study pharyngitis endpoint","Proportion of participants in each arm who develop pharyngitis according to pre-defined clinical and microbiological diagnostic criteria, comprising sore throat, physical examination signs of pharyngitis and tonsillitis, and microbiological confirmation of S. pyogenes by culture and nucleic acid amplification test of throat swabs","Up to 5 days after the challenge dose of M1 S. pyogenes is administered.",[14,18,22,26,30,33,36,39,42],{"measure":15,"description":16,"timeFrame":17},"Changes in Streptococcus pyogenes pharyngeal colonisation (infection) - proportion of participants in each arm with established colonisation as measured by throat swab culture and strain-specific qPCR","To evaluate effects of IVIg on pharyngeal colonisation by M1 S. pyogenes after challenge:\n\nBacterial colonisation measured by culture and strain-specific qPCR of throat swabs (including participants without symptoms).\n\nProportion of participants in each arm with established colonisation (at 2 or more timepoints at least 12 hours apart).\n\nComparison of overall colonisation density between participants in each arm (i.e. area under the curve of sequential qPCR results).","Up to 40 days after the challenge dose of M1 S. pyogenes is administered.",{"measure":19,"description":20,"timeFrame":21},"Changes in early inflammatory response between participants in each arm - as measured by high-dimensional flow cytometry and multiplex cytokine and chemokine assays","To evaluate effects of IVIg on the early inflammatory response changes to M1 S. pyogenes challenge.\n\nComparison of baseline and subsequent peripheral blood leukocyte, cytokine and chemokine levels between participants in each arm.","Up to 16 days after the challenge dose of M1 S. pyogenes is administered",{"measure":23,"description":24,"timeFrame":25},"Changes in serum opsonophagocytic activity between participants in each arm","To characterise changes in serum opsonophagocytic activity against the M1 challenge strain (Opsonic Index; OI) from baseline (pre-IVIg or placebo) to the pre-challenge timepoint (Day 0).","Prior to passive immunisation (IVIg or placebo) and prior to challenge (Day 0).",{"measure":27,"description":28,"timeFrame":29},"Changes in serum antigen-specific binding antibody responses between participants in each arm","Changes in serum IgG levels to: type-specific M1 peptide and other S. pyogenes antigens, including candidate vaccine antigens.","Baseline (Screening) through to study completion, an average of 3 months for each participant.",{"measure":31,"description":32,"timeFrame":29},"Changes in SpyCEP specific functional antibody responses between participants in each arm","To evaluate S. pyogenes SpyCEP antigen-specific functional antibody responses at baseline, pre-challenge, and post-challenge (IL-8 cleavage inhibition assay.).",{"measure":34,"description":35,"timeFrame":29},"Changes in SLO specific functional antibody responses between participants in each arm","To evaluate S. pyogenes SLO antigen-specific functional antibody responses at baseline, pre-challenge, and post-challenge (haemolysis inhibition assay).",{"measure":37,"description":38,"timeFrame":29},"Changes in Group A Carbohydrate (GAC) specific functional antibody responses between participants in each arm","To evaluate S. pyogenes GAC antigen-specific functional antibody responses at baseline, pre-challenge, and post-challenge (bead-based antibody dependent phagocytosis).",{"measure":40,"description":41,"timeFrame":29},"Changes in SpyAD specific functional antibody responses between participants in each arm","To evaluate S. pyogenes SpyAD antigen-specific functional antibody responses at baseline, pre-challenge, and post-challenge (bead-based antibody dependent phagocytosis).",{"measure":43,"description":44,"timeFrame":45},"Changes in whole blood antigen-specific T cell stimulation results between participants in each arm","To evaluate S. pyogenes antigen-specific cellular immunity pre-challenge and post-challenge\n\n* 'Immuno-T' in-tube whole blood interferon gamma release assay\n* Additional whole blood stimulation studies with cytokine release and flow cytometry readouts","Baseline (Screening) through to study completion, an average of 3 months for each participant",null,{"allocation":48,"interventionModel":49,"interventionModelDescription":50,"primaryPurpose":51,"observationalModel":46,"timePerspective":46,"maskingInfo":52},"RANDOMIZED","PARALLEL","Blinded, randomised, placebo controlled, human challenge trial.","BASIC_SCIENCE",{"masking":53,"maskingDescription":46,"whoMasked":54},"QUADRUPLE",[55,56,57,58],"PARTICIPANT","CARE_PROVIDER","INVESTIGATOR","OUTCOMES_ASSESSOR","CHIVAS-IgG is a blinded randomised placebo controlled human challenge trial of passive immunisation with intravenous immunoglobulin (IVIg) or placebo, prior to direct oropharyngeal inoculation of M1 Streptococcus pyogenes at the beginning of an inpatient period of up to 5 days, followed by 1 month outpatient follow-up.\n\nThe goal of CHIVAS-IgG is to directly assess correlates of protection against S. pyogenes for the first time. CHIVAS-IgG is part of the Protective Immunity against Strep A (PISA) project, funded by the Wellcome Trust towards identifying and using correlates of immune protection to accelerate vaccine development. The primary objective of the CHIVAS-IgG study is to directly test whether passively administered antibodies in the form of human intravenous immunoglobulin (IVIg) are protective against M1UK S. pyogenes experimental human pharyngitis.\n\nAs part of PISA, CHIVAS-IgG will: 1) advance development of standardised validated immunoassays for implementation in vaccine trials, including new reference materials; 2) Directly assess correlates of protection to complement natural immunity insights from CHIM studies and natural cohorts; 3) Provide evidence that the pharyngitis human challenge model can be used to evaluate protective efficacy; and 4) Drive discovery science in microbiology and immunology.\n\nMechanistic correlates of protection offer extremely valuable insights for vaccine development - focussing vaccination strategies towards known protective mechanisms and antigens. IVIg is included as a positive control in the S. pyogenes HL-60 opsonophagocytic assay (and many other functional assays) and has reliably high bactericidal activity against all strains tested. The investigators will enrol participants with low baseline titres to a type-specific M1 peptide and randomise 1:1 to receive IVIg (at least 400 mg\u002Fkg) or 0.9% sodium chloride infusion. A risk assessment has confirmed that this IVIg dose should be well-tolerated. Additionally, several simple mitigation strategies against reactions to IVIg are incorporated into the study protocol. Participants, clinical staff, and outcome assessors will be blinded to group allocation. Within 10 days of the infusion, participants will be challenged and monitored along lines modelled on the recently completed CHIVAS-M1 study (NCT06992141).",[61,68],{"label":62,"type":63,"description":64,"interventionNames":65},"Passive immunisation (intravenous immunoglobulin)","EXPERIMENTAL","Participants allocated to this arm will receive an intravenous infusion of between 400 and 600 mg (4 to 6 mL) per kg of human immunoglobulin (KIOVIG® 10%).",[66,67],"Biological: Streptococcus pyogenes M1 challenge strain","Biological: Intravenous immunoglobulin (IVIG)",{"label":69,"type":70,"description":71,"interventionNames":72},"Passive immunisation (saline placebo)","PLACEBO_COMPARATOR","Participants allocated to this arm will receive an intravenous infusion of between 4 and 6 mL per kg of 0.9% sodium chloride.",[66,73],"Drug: Saline (NaCl 0,9 %) (placebo)",[75,80,84],{"type":76,"name":77,"description":78,"armGroupLabels":79,"otherNames":46},"BIOLOGICAL","Streptococcus pyogenes M1 challenge strain","All participants will be inoculated by direct oropharyngeal swab application from vials containing 1-5 x 10\\^5 CFU bacteria in 1 mL animal-free liquid media.",[62,69],{"type":76,"name":81,"description":82,"armGroupLabels":83,"otherNames":46},"Intravenous immunoglobulin (IVIG)","Participants will be randomised 1:1 to receive IVIg or placebo (0.9% sodium chloride) prior to pharyngeal challenge with Streptococcus pyogenes.",[62],{"type":85,"name":86,"description":82,"armGroupLabels":87,"otherNames":88},"DRUG","Saline (NaCl 0,9 %) (placebo)",[69],[89,90],"0.9% sodium chloride","normal saline",[92],{"name":93,"affiliation":5,"role":94},"Joshua Osowicki, MBBS, BMedSci, FRACP, PhD","PRINCIPAL_INVESTIGATOR",[96],{"name":97,"role":98,"phone":99,"phoneExt":46,"email":100},"Trial Coordinator","CONTACT","+61 3 8341 6200","kristy.azzopardi@mcri.edu.au",[102],{"facility":103,"status":46,"city":104,"state":105,"zip":106,"country":107,"countryCode":108,"cosmosGeoPoint":109,"geoPoint":114,"contacts":115},"Doherty Clinical Trials Ltd","Melbourne","Victoria","3002","Australia","AU",{"type":110,"coordinates":111},"Point",[112,113],144.96332,-37.814,{"lat":113,"lon":112},[116],{"name":117,"role":94,"phone":46,"phoneExt":46,"email":46},"Julia Marshall, MBBS, MD, PhD",{"type":119,"investigatorFullName":46,"investigatorTitle":46,"investigatorAffiliation":46,"oldNameTitle":46,"oldOrganization":46},"SPONSOR",[121,123,125,127,129],{"name":122,"class":6},"University of Melbourne",{"name":124,"class":6},"University of Sheffield",{"name":126,"class":6},"Medical Research Council Unit, The Gambia",{"name":128,"class":6},"Walter and Eliza Hall Institute of Medical Research",{"name":130,"class":6},"London School of Hygiene and Tropical Medicine","100659377","phase-1-stopping-strep-throat-with-antibodies-in-healthy-adults-100659377",false,"NCT07864350","Stopping Strep Throat With Antibodies in Healthy Adults.","CHIVAS-IgG: A Blinded, Randomised, Placebo-Controlled Human Infection Trial in Healthy Adults of Passive Immunisation With Intravenous Immunoglobulin to Explore Protective Immunity Against Strep A Pharyngitis (A PISA Consortium Study).","CHIVAS-IgG","Inclusion Criteria:\n\n1. Males or females, aged 18 - 40 years (inclusive) on the day of informed consent.\n2. Medically healthy, which can be determined by medical history, physical examination, BMI, transthoracic echocardiogram, non-clinically significant laboratory profiles, vital signs, and 12-lead ECG at screening, as deemed necessary by the research physician or investigator.\n3. Normal systolic (SBP) and diastolic blood pressure (DBP), i.e. SBP 90 - 140 mmHg and DBP of 60 - 90 mmHg or as determined by the research physician or investigator. Vital signs can be repeated up to two times.\n4. Normal resting heart rate (HR), i.e. 50-100 bpm or as determined by the research physician or investigator (confirmed by one repeat at screening).\n5. Female participants who are not pregnant and not breastfeeding, or postmenopausal for at least 1 year (non-menstruating for at least 1 year, as confirmed by follicle-stimulating hormone \\[FSH\\]), or surgically sterile for at least 6 months prior to dosing.\n6. Female participants of childbearing potential must not be planning to conceive or contribute to pregnancy and will be required to use an effective form of contraception from the time of signing informed consent until the final outpatient visit approximately 1 month following the inpatient challenge admission.\n7. Male participants must not have a pregnant partner and must agree to use condoms as a method of contraception, with sexually active females of childbearing potential, from the time of signing informed consent until the final outpatient visit approximately 1 month following the inpatient challenge admission. Male participants must also agree not to donate sperm from Day 0 to the final visit. Male participants who are surgically sterilised, performed at least 6 months prior to screening, may be enrolled.\n8. Must be willing and able to read, understand, and sign the participant information and consent form. Willing to comply with all study requirements, including the inpatient period and outpatient visits for the duration of the study (approx. 3 months).\n9. Willing to abstain from the use of mouthwash from the day of screening until the first outpatient visit at one week post discharge.\n\nExclusion Criteria:\n\nRelated to passive immunisation:\n\n1. History of anaphylactic or severe systemic reaction to human immune globulin\n2. Known serum IgA deficiency\n3. Received blood, blood products and\u002For plasma derivatives or any parenteral immunoglobulin preparation within 3 months of informed consent.\n4. Donated blood or plasma within 1 month of informed consent.\n\n   Related to S. pyogenes challenge:\n5. Known hypersensitivity to more than two of the following antibiotics: penicillin, other beta-lactam antibiotic(s), azithromycin, or clindamycin.\n6. Known hypersensitivity to soya protein (soy).\n7. Have participated in previous S. pyogenes challenge studies (with application of challenge agent).\n8. Intolerance of throat swab procedure (exaggerated gag reflex).\n9. Personal or family history of severe S. pyogenes infection (toxic shock syndrome, necrotizing fasciitis, bloodstream infection, pleural empyema, meningitis) or post-infectious sequelae (such as acute rheumatic fever, rheumatic heart disease, post-streptococcal glomerulonephritis).\n10. History of tonsillectomy, adenoidectomy, thymectomy, or splenectomy.\n11. Evidence of pre-existing immunity to the challenge strain, as determined by elevated M1 type-specific serum IgG antibodies (i.e. ELISA optical density \\\u003C 0.3 at 1:100 serum dilution).\n12. A positive point of care (POC) test for S. pyogenes on screening throat swab.\n\nGeneral health:\n\n1. History of any clinically important cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator.\n2. Significant history of hospitalisation for illness within the six months prior to enrolment into the study, or major surgery within the 12 months prior to enrolment into the study, as assessed by research physician or investigator.\n3. Known or suspected autoimmune disease or impairment\u002Falteration of immune function resulting from:\n\n   1. Congenital or acquired immunodeficiency (including IgA deficiency)\n   2. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months.\n4. History of a severe drug reaction or severe allergic reaction (eg. anaphylaxis, convulsions) or clinically significant allergic disease diagnosed by a physician.\n5. Clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea.\n6. Any vaccination within the previous 28 days or use of any antibiotic therapy during the 14 days before challenge.\n7. Presence of an acute infectious disease or febrile illness (e.g., sub-lingual temperature ≥ 38.5°C) within the five days prior to inoculation.\n8. Significant acute or chronic infection within 14 days prior to inoculation that the research physician or investigator deems may compromise participant safety.\n9. Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis, ECG or transthoracic echocardiogram.\n10. Positive serologic results for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and\u002For hepatitis C virus (HCV).\n11. Ex-smoker with a \\>10 pack per year smoking history (≥20 cigarettes per day for \\>10 years or ≥2 30 g tobacco pouches per week for \\>10 years) or a current smoker who is unable to stop smoking for the duration of the study. Vaping is allowed, except if a participant is unable to abstain from vaping during the inpatient period.\n12. History or presence of alcohol abuse (defined as regular alcohol consumption of more than 40g\u002F4 standard drinks per day) or drug habituation, or any prior intravenous usage of an illicit substance.\n13. A positive alcobreath test at screening or admission.\n14. A positive urine drug test at screening or admission (e.g., amphetamines, barbiturates, benzodiazepines, cocaine, methylenedioxymethamphetamine \\[MDMA\\], methamphetamine, methadone, opiates, phencyclidine \\[PCP\\] and tetrahydrocannabinol \\[THC\\]) unless there is an explanation acceptable to the Investigator (e.g. the participant has stated in advance that they consumed a prescription or OTC product which contained the detected drug) and the participant has a negative urine drug screen on retest.\n15. Systemic corticosteroid in the 14 days prior to admission, or for more than seven consecutive days within the past 3 months, or anticipated use during the study period.\n16. Any chronic (more than 1 month) use of inhaled high potency corticosteroids (budesonide 800 μg or fluticasone 750 μg per day).\n17. Intranasal corticosteroid use is not allowed in the 14 days prior to admission, during the inpatient period, and is discouraged prior to the first outpatient visit. Topical corticosteroid use is allowed.\n18. Any use of drugs which may suppress the hypothalamic-pituitary-adrenal (HPA) axis such as adrenocorticotrophic hormone (ACTH) within the previous 3 months.\n19. Any anti-inflammatory drugs (besides sporadic use of non-steroidal anti-inflammatory drugs), immunomodulators (such as monoclonal antibodies) or anticoagulants in the previous 3 months, or anticipated use of such drugs during the study period.\n20. Use of any other prescription drugs within 14 days or 5 half-lives (whichever is the longer) prior to the challenge inoculum administration. Exceptions include individuals with established, stable health conditions on long-term medication, such as:\n\n    * Individuals diagnosed with anxiety, depression, and attention deficit hyperactivity disorder (ADHD) who are well established on pharmacological therapy (i.e. the same medication for at least 6 months and the same dose for at least 3 months) may be considered for inclusion.\n    * Individuals with well-controlled asthma on inhaled corticosteroid at the same dose for more than 6 months (doses must be less than budesonide 800 μg or fluticasone 750 μg per day) or oral leukotriene modifiers (such as montelukast) and no hospital admissions in the past 2 years may be considered for inclusion.\n    * Oral contraceptive pill or contraceptive depot, implant, or device.\n21. Use of non-prescription drugs and herbal supplements (such as St John´s Wort) within 14 days or 5 half-lives (whichever is the longer) prior to the challenge inoculum administration. Exceptions include:\n\n    * Use of vitamin supplements taken at standard doses.\n    * Individuals on nicotine replacement therapies for at least 1 month can participate in the study if they have \\\u003C10 pack per year smoking history (10 pack years is equivalent to ≥20 cigarettes per day for 10 years).\n    * Individuals who use protein supplements regularly may continue to use these during the trial, including the inpatient phase, however during the inpatient phase use should not exceed 2 x 30 g protein shakes per day.\n22. Participation in another research study within the 30 days prior to enrolment involving an investigational product or other intervention that might affect risk of invasive S. pyogenes infection or compromise the integrity of the study.\n23. Participation in a research study that involved blood sampling of more than 450 mL of blood within 3 months of informed consent.\n24. History of severe infections requiring hospitalisation for intravenous antibiotics (within the last 10 years). Exceptions to this would include a short course of intravenous antibiotics for appendicitis, biliary sepsis, diverticulitis, pyelonephritis and cellulitis or a similar non-severe infection.\n25. History of cancer (except adequately treated squamous cell or basal cell carcinoma of the skin and cervical intraepithelial neoplasia).\n26. Presence of implants or prostheses (e.g. artificial joints, pacemakers) deemed significant for infective complications as assessed by research physician or investigator. Participants with cosmetic implants or prostheses may be included, as per principal investigator's discretion.\n27. Any significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or may influence the results of the study, or the participant's ability to participate in the study.\n28. Any employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child whether biological or legally adopted.\n\nParticipants who are excluded from participation on study days for any of the above reasons may be eligible to participate on a postponed schedule of up to one week, if the Investigator considers this appropriate. Re-screening will be allowed if the investigator considers the cause of the initial screening failure to be acute and reversible.",true,"ALL","18 Years","40 Years",{"count":144,"type":145},60,"ESTIMATED","INTERVENTIONAL",[148],"PHASE1","This research group has previously established a safe and reliable model of experimental human streptococcal pharyngitis (a 'strep throat' human challenge model). The CHIVAS-IgG study will use this model to understand the ways in which antibodies help protect humans against strep throat infections.\n\nCarefully screened healthy adults who are at very low risk of complicated strep disease will be admitted to a clinical trials unit where they will be randomly allocated to receive a licensed commercial 'intravenous immunoglobulin' product that is a mixture of antibodies from thousands of humans, or a placebo ('saline' or salty water), by intravenous injection.\n\nAbout a week after the injection of antibodies or saline, they will have strep throat bacteria (Streptococcus pyogenes) 'painted' with a swab on the back of their throat, as this research group has done previously for over 100 healthy adults. The participants will be observed closely for about 5 days to see if they develop symptoms (sore throat) and signs (red throat, big tonsils, sore glands) of strep throat. During that time, multiple throat and nasal swabs will be collected along with saliva samples, blood tests, and photos. Before discharge from the clinical trials unit, every participant will be treated with antibiotics to make sure any strep bacteria is removed.\n\nParticipants will return for study visits at about 1 week and 1 month later, to check on how they are feeling and to collect more samples to understand how their immune system responds to the strep challenge.\n\nThis study is an important step on the way to developing a vaccine to prevent strep throat, strep skin infections, and dangerous Streptococcus pyogenes diseases like invasive infections and post-infectious problems like rheumatic heart disease.",[151],"Streptococcal Pharyngitis",[153,154,155,156,157,158,159],"Streptococcus pyogenes","Group A Streptococcus","Strep A","Controlled Human Infection Model","Controlled Human Infection Study","Human Challenge","Pharyngitis","NOT_YET_RECRUITING","2026-10-02",{"date":163,"type":164},"2026-10-07","ACTUAL",{"date":166,"type":145},"2026-10",{"date":168,"type":145},"2027-07",{"name":5,"class":6},1]