Stopping Strep Throat With Antibodies in Healthy Adults.

NCT07864350 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: CHIVAS-IgG308941/Z/23/Z
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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. Carefully 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. About 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. Participants 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. This 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.

Conditions

Streptococcal Pharyngitis

Keywords

Streptococcus pyogenes; Group A Streptococcus; Strep A; Controlled Human Infection Model; Controlled Human Infection Study; Human Challenge; Pharyngitis

Outcome Measures

Primary Outcomes (1)

• 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.

Secondary Outcomes (9)

• 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

  Up to 40 days after the challenge dose of M1 S. pyogenes is administered.

• Changes in early inflammatory response between participants in each arm - as measured by high-dimensional flow cytometry and multiplex cytokine and chemokine assays

  Up to 16 days after the challenge dose of M1 S. pyogenes is administered

• Changes in serum opsonophagocytic activity between participants in each arm

  Prior to passive immunisation (IVIg or placebo) and prior to challenge (Day 0).

• Changes in serum antigen-specific binding antibody responses between participants in each arm

  Baseline (Screening) through to study completion, an average of 3 months for each participant.

• Changes in SpyCEP specific functional antibody responses between participants in each arm

  Baseline (Screening) through to study completion, an average of 3 months for each participant.

Study Arms (2)

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%).

Biological: Streptococcus pyogenes M1 challenge strain; Biological: Intravenous immunoglobulin (IVIG)

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.

Biological: Streptococcus pyogenes M1 challenge strain; Drug: Saline (NaCl 0,9 %) (placebo)

Interventions

Streptococcus pyogenes M1 challenge strain BIOLOGICAL

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.

Passive immunisation (intravenous immunoglobulin); Passive immunisation (saline placebo)

Intravenous immunoglobulin (IVIG) BIOLOGICAL

Participants will be randomised 1:1 to receive IVIg or placebo (0.9% sodium chloride) prior to pharyngeal challenge with Streptococcus pyogenes.

Passive immunisation (intravenous immunoglobulin)

Saline (NaCl 0,9 %) (placebo) DRUG

Participants will be randomised 1:1 to receive IVIg or placebo (0.9% sodium chloride) prior to pharyngeal challenge with Streptococcus pyogenes.

Also known as: 0.9% sodium chloride, normal saline

Passive immunisation (saline placebo)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females, aged 18 - 40 years (inclusive) on the day of informed consent.
• 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.
• 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.
• 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).
• 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.
• 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.
• 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.
• 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).
• Willing to abstain from the use of mouthwash from the day of screening until the first outpatient visit at one week post discharge.

You may not qualify if:

• Related to passive immunisation:
• History of anaphylactic or severe systemic reaction to human immune globulin
• Known serum IgA deficiency
• Received blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 3 months of informed consent.
• Donated blood or plasma within 1 month of informed consent.
• Related to S. pyogenes challenge:
• Known hypersensitivity to more than two of the following antibiotics: penicillin, other beta-lactam antibiotic(s), azithromycin, or clindamycin.
• Known hypersensitivity to soya protein (soy).
• Have participated in previous S. pyogenes challenge studies (with application of challenge agent).
• Intolerance of throat swab procedure (exaggerated gag reflex).
• 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).
• History of tonsillectomy, adenoidectomy, thymectomy, or splenectomy.
• Evidence of pre-existing immunity to the challenge strain, as determined by elevated M1 type-specific serum IgG antibodies (i.e. ELISA optical density \< 0.3 at 1:100 serum dilution).
• A positive point of care (POC) test for S. pyogenes on screening throat swab.
• General health:

Sponsors & Collaborators

• Murdoch Childrens Research Institute: lead
• University of Melbourne: collaborator
• University of Sheffield: collaborator
• Medical Research Council Unit, The Gambia: collaborator
• Walter and Eliza Hall Institute of Medical Research: collaborator
• London School of Hygiene and Tropical Medicine: collaborator

Study Sites (1)

Doherty Clinical Trials Ltd

Melbourne, Victoria, 3002, Australia

Location

Related Publications (3)

• Hla TK, Osowicki J, Marsh JA, Salman S, Page-Sharp M, Yoo O, Azzopardi K, Morici M, Batty KT, Barr RK, Enkel SL, Kado J, Hatchuel L, Fulurija A, McCarthy JS, Snelling TL, Steer AC, Carapetis J, Manning L. Establishing the lowest penicillin concentration to prevent pharyngitis due to Streptococcus pyogenes using a human challenge model (CHIPS): a randomised, double-blind, placebo-controlled trial. Lancet Microbe. 2025 May;6(5):101038. doi: 10.1016/j.lanmic.2024.101038. Epub 2025 Mar 26.

  PMID: 40157384 BACKGROUND

• Osowicki J, Azzopardi KI, Baker C, Waddington CS, Pandey M, Schuster T, Grobler A, Cheng AC, Pollard AJ, McCarthy JS, Good MF, Walker MJ, Dale JB, Batzloff MR, Carapetis JR, Smeesters PR, Steer AC. Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study. Vaccine. 2019 Jun 6;37(26):3485-3494. doi: 10.1016/j.vaccine.2019.03.059. Epub 2019 May 14.

  PMID: 31101422 BACKGROUND

• Osowicki J, Azzopardi KI, Fabri L, Frost HR, Rivera-Hernandez T, Neeland MR, Whitcombe AL, Grobler A, Gutman SJ, Baker C, Wong JMF, Lickliter JD, Waddington CS, Pandey M, Schuster T, Cheng AC, Pollard AJ, McCarthy JS, Good MF, Dale JB, Batzloff M, Moreland NJ, Walker MJ, Carapetis JR, Smeesters PR, Steer AC. A controlled human infection model of Streptococcus pyogenes pharyngitis (CHIVAS-M75): an observational, dose-finding study. Lancet Microbe. 2021 Jul;2(7):e291-e299. doi: 10.1016/S2666-5247(20)30240-8. Epub 2021 Apr 15.

  PMID: 35544165 BACKGROUND

Related Links

• Clinical trial site

MeSH Terms

Conditions

Pharyngitis

Interventions

Immunoglobulins, Intravenous; Sodium Chloride; Saline Solution

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Pharyngeal Diseases; Stomatognathic Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Joshua Osowicki, MBBS, BMedSci, FRACP, PhD

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Trial Coordinator

CONTACT

+61 3 8341 6200; kristy.azzopardi@mcri.edu.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Blinded, randomised, placebo controlled, human challenge trial.

Study Record Dates

• First Submitted: September 28, 2026
• First Posted: October 7, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: October 7, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: De-identified IPD will be available at the end of the clinical trial. IPD will be stored for 15 years afterwards in concordance with the International Council for Harmonisation (ICH) guidelines for clinical trial data.
• Access Criteria: Only authorised study site staff will have access to source documentation. De-identified IPD will be shared with the sponsor. De-identified IPD will be shared with collaborators only in specific circumstances where sharing the data will benefit and extend research collaborations.

Locations

AU (1)