CompletedPhase 1

Controlled Human Infection for Vaccination Against Streptococcus Pyogenes

Australia25 participantsStarted 2018-07-10

Plain-language summary

Group A Streptococcus (GAS) infection is a major cause of death and disability globally with a disproportionately high burden in settings of disadvantage worldwide. Acute infections due to GAS range from very common superficial skin infections (\>150 million prevalent cases) and pharyngitis (over 600 million incident cases) to life-threatening invasive disease (\>600,000 incident cases) such as necrotising fasciitis. Post-infectious GAS sequelae of GAS include acute rheumatic fever (ARF, \~500,000 incident cases) leading to rheumatic heart disease (RHD, \~34 million prevalent cases), and acute glomerulonephritis. The health services impact of GAS disease in all its forms is immense and strikes at every level from primary to intensive care. Controlled human infection models (CHIMs) have a long history of critical contributions to vaccine development. Data from CHIMs meeting modern scientific, regulatory, and ethical standards, are aiding efforts to control over 25 major human pathogens, including bacteria (e.g. pneumococcus, cholera), viruses (e.g. respiratory syncytial virus, influenza), and parasites (e.g. malaria, schistosomiasis). A reliable and safe controlled human infection model of GAS pharyngitis will be an important part of the global vaccine development effort. To build the model, the investigators are undertaking a dose-ranging study using an observational, dose-escalation, inpatient trial to determine the dose of GAS administered by direct oropharyngeal inoculation (bacteria 'painted' onto throat) required to reliably produce a pharyngitis attack rate of ≥ 60% in carefully screened healthy adult volunteers.

Who can participate

Age range

18 Years – 40 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Males or females, aged 18 - 40 years (inclusive) on the day of informed consent. * Medically healthy, determined by medical history, physical examination, transthoracic echocardiogram, non-clinically significant laboratory profiles, vital signs, and 12-lead ECG at screening, as deemed by the investigator. * No active or chronic diseases/disorders, no history of hospitalisation for illness within the six months prior to enrolment into study, and no major surgery within the 12 months prior to enrolment into study. * Body mass index of 18.0 - 32.0 kg/m2 and body weight ≥ 50.0kg * Systolic blood pressure (SBP) of 90 mmHg - 140 mmHg and diastolic blood pressure (DBP) of 50 mmHg - 90 mmHg. Vital signs can be repeated up to two times. * Resting heart rate (HR), as measured by ECG of 40bpm - 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. * All male and females of childbearing potential must agree to use two forms of acceptable contraception from the time of signing informed consent until 30 days after final dose of rifampicin. * Acceptable forms of contraception include: barrier method (eg. condom, diaphragm); pharmacological hormonal methods (oral contraceptive pill, long-acting implantable, intrauterine device). * Rifampicin may reduce the activity of oral and …

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Proportion of participants at each GAS M75 dose level meeting the study pharyngitis endpoint

Timeframe: Up to 6 days after challenge dose administered.

Trial details

NCT IDNCT03361163

SponsorAndrew Steer

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2019-09-28

View on ClinicalTrials.gov More Streptococcus Pyogenes Pharyngitis trials