A Strep Throat Controlled Human Infection Trial in Healthy Adults

NCT06992141 | Completed Early Phase 1 DMC

• 1 other identifier: CHIVAS-M1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This aim of this study is to further develop a new way to study the bacteria that causes pharyngitis (strep throat). The scientific name for this bacterium is Streptococcus pyogenes and it is commonly known as Strep A. Strep A is a common type of bacteria that can cause various infections. These range from skin infections and strep throat to more serious conditions like rheumatic heart disease. In recent years there has been an increase in severe Strep A infections in most countries. Many of these cases have been reported in the news. Human challenge models are studies which allow researchers to study organisms that cause infections in humans. In this human challenge model study, healthy participants will be carefully exposed to a specific type of Strep A under controlled conditions to cause sore throat and learn more about how Strep A causes infection. The study team has already developed a safe human challenge model using a strain of Strep A called M75. This study will use a different strain of Strep A, called M1. The main goal of this study is to check if the procedure is safe for participants and to understand how the participant's body responds to M1 Strep A. The study will explore:

1. 1.How much M1 Strep A is required to cause an infection.
2. 2.How M1 Strep A grows in the body.
3. 3.How the body reacts to M1 Strep A.

Conditions

Streptococcus Pyogenes Pharyngitis; Streptococcus Infection

Keywords

Streptococcus pyogenes; Streptococcus pyogenes pharyngitis; Controlled Human Infection Model; S. pyogenes M1UK

Outcome Measures

Primary Outcomes (1)

• The proportion of participants at each dose level of M1 S. pyogenes who reach the study pharyngitis endpoint

  The proportion of participants at each M1 S. pyogenes dose level who develop pharyngitis, using a combined clinical-microbiological definition 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

Study Arms (1)

Human challenge participants

EXPERIMENTAL

Participants will be allocated a dose of M1 S. pyogenes sequentially by date of challenge based on the attack rate in the preceding participants. Up to 4 dose levels will be tested commencing at 1-5 x10\^5 CFU/mL, increasing by 1 log to a maximum dose of 1-5 x 10\^7 CFU/mL, or decreasing by 1 log to a minimum dose of 1-5 x 10\^4 CFU/mL.

Biological: Streptococcus pyogenes M1UK strain MCRI0102

Interventions

Streptococcus pyogenes M1UK strain MCRI0102 BIOLOGICAL

Human challenge with S. pyogenes M1UK strain MCRI0102

Human challenge participants

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.
• Systolic blood pressure (SBP) of 90 mmHg - 140 mmHg and diastolic blood pressure (DBP) of 60 mmHg - 90 mmHg. Vital signs can be repeated up to two times.
• Resting heart rate (HR) of 55-100 bpm (confirmed by one repeat at screening).
• Females must be non-pregnant, non-lactating, or postmenopausal for at least 1 year (as confirmed by follicle-stimulating hormone \[FSH\]), or surgically sterile for at least 6 months prior to dosing.
• Females of childbearing potential will be required to use an effective form of contraception from the time of signing informed consent until the second planned outpatient visit approximately 1 month following the inpatient challenge admission.
• Males must not have a pregnant partner and must agree to use condoms as a method of contraception from the time of signing informed consent until the second planned outpatient visit approximately 1 month following the inpatient challenge admission.
• 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:

• 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.
• Significant history of hospitalisation for illness within the six months prior to enrolment into study, or major surgery within the 12 months prior to enrolment into study, as assessed by research physician or investigator.
• History of tonsillectomy, adenoidectomy or splenectomy.
• Known or suspected autoimmune disease or impairment/alteration of immune function resulting from:
• Congenital or acquired immunodeficiency (including immunoglobulin A \[IgA\] deficiency)
• Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months.
• History of a severe drug reaction or severe allergic reaction (eg. anaphylaxis, convulsions) or clinically significant allergic disease diagnosed by a physician.
• 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).
• Clinically significant disease or any condition or disease that might affect drug absorption, distribution or excretion, e.g. gastrectomy, diarrhoea.
• Any vaccination within the last 28 days or use of any antibiotic therapy during the 14 days before challenge.
• Presence of an acute infectious disease or febrile illness (e.g., sub-lingual temperature ≥ 38.5°C) within the five days prior to inoculation.
• Significant acute or chronic infection within 14 days prior to inoculation that the research physician or investigator deems may compromise participant safety.
• Any clinically significant abnormal finding on biochemistry or haematology blood tests, urine analysis, ECG or transthoracic echocardiogram.
• Positive serologic results for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HBsAg), and/or hepatitis C virus (HCV) antibodies.
• Ex-smoker with a \>10 pack per year smoking history or a current smoker who is unable to stop smoking for the duration of the study.

Sponsors & Collaborators

• University of Auckland, New Zealand: collaborator
• University of Melbourne: collaborator
• University of Wollongong: collaborator
• Université Libre de Bruxelles: collaborator
• University of California, San Diego: collaborator
• Leducq Foundation: collaborator
• National Health and Medical Research Council, Australia: collaborator
• Monash University: collaborator
• Duke University: collaborator
• The University of Queensland: collaborator
• Doherty Clinical Trials Ltd: collaborator
• Murdoch Childrens Research Institute: lead

Study Sites (1)

Doherty Clinical Trials Ltd

Melbourne, Victoria, 3002, Australia

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Streptococcal Infections

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Joshua Osowicki, FRACP PhD

  Murdoch Childrens Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is an observational, sequential, dose escalation/de-escalation study with 4 predetermined doses of bacteria for human challenge. The aim is to reliably and safely cause pharyngitis in greater than or equal to 60% of participants. The starting dose is based upon the successful dose from the previous human challenge study (CHIVAS- M75) and escalation/de-escalation decisions will be based upon the number of participants diagnosed with pharyngitis in each cohort of 10-20 participants.

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: May 28, 2025
• Study Start: July 24, 2025
• Primary Completion: October 31, 2025
• Study Completion: February 16, 2026
• Last Updated: March 16, 2026

Record last verified: 2026-03

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. Collaborators in this study are located in the following countries: Australian (Victoria, Queensland, Western Australia, and New South Wales), New Zealand, Belgium, Netherlands, the UK, and the US.

Locations

AU (1)