Controlled Human Infection for Vaccination Against Streptococcus Pyogenes

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.

Conditions

• Streptococcus Pyogenes Pharyngitis
• Streptococcus Pharyngitis
• Strep Throat
• Streptococcus Pyogenes Infection
• Group A Streptococcus: B Hemolytic Pharyngitis
• Group A Streptococcal Infection
• Gram-Positive Bacterial Infections
• Bacterial Infections

Interventions

BIOLOGICAL

emm75 Streptococcus pyogenes (GAS M75, strain 611024)

Direct oropharyngeal application by swab following immersion in a solution containing a specified concentration (dose) of GAS M75.

Sponsors & Collaborators

• University of Melbourne

  collaborator OTHER

• Nucleus Network Ltd

  collaborator OTHER

• National Health and Medical Research Council, Australia

  collaborator OTHER

• Telethon Kids Institute

  collaborator OTHER

• The Peter Doherty Institute for Infection and Immunity

  collaborator OTHER

• Queen Fabiola Children's University Hospital

  collaborator OTHER

• Griffith University

  collaborator OTHER

• University of Wollongong

  collaborator OTHER

• The University of Queensland

  collaborator OTHER

• University of Auckland, New Zealand

  collaborator OTHER

• University of Tennessee

  collaborator OTHER

• Andrew Steer

  lead OTHER

Principal Investigators

• Janet Wong, MBBS,BSc · Senior Medical Officer, Nucleus Network Limited

• Andrew C Steer, MBBS,MPH,PhD · Group A Streptococcal Research Group, Murdoch Children's Research Institute

Study Design

Purpose

BASIC_SCIENCE

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-07-10

Primary Completion

2019-09-28

Completion

2020-04-21

Countries

• Australia

Study Locations