Ignite Creation Date:
2024-05-06 @ 10:49 AM
Last Modification Date:
2024-10-26 @ 12:36 PM
Study NCT ID:
NCT03361163
Status:
COMPLETED
Last Update Posted:
2020-05-19
First Post:
2017-11-14
Brief Title:
Controlled Human Infection for Vaccination Against Streptococcus Pyogenes
Sponsor:
Andrew Steer
Organization:
Murdoch Childrens Research Institute
Study Overview
Official Title:
Group A Streptococcal Human Challenge Study Building a Pharyngitis Model to Accelerate Vaccine Development
Status:
COMPLETED
Status Verified Date:
2020-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CHIVAS
Brief 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 600000 incident cases such as necrotising fasciitis Post-infectious GAS sequelae of GAS include acute rheumatic fever ARF 500000 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 eg pneumococcus cholera viruses eg respiratory syncytial virus influenza and parasites eg 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
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 eg pneumococcus cholera viruses eg respiratory syncytial virus influenza and parasites eg 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
Detailed Description:
Group A Streptococcus GAS is a ubiquitous human pathogen Its impact begins in early childhood and is felt most by those who have the least Globally the health services impact of GAS disease in all its forms is immense and strikes at every level from primary to intensive care Despite recognition of the need for GAS vaccine development there are major obstacles impeding progress A human challenge model promises to help to shift inertia in GAS vaccine development
The objective of this study is to use an observational dose-escalation inpatient trial to determine the dose of GAS administered by direct oropharyngeal inoculation required to reliably produce a pharyngitis attack rate of 60 in carefully screened healthy adult volunteers A GAS strain has been specially selected and prepared for this study to ensure safety and clinical relevance Potential participants aged 18 to 40 years the age range associated with the lowest risk of invasive GAS disease will be carefully screened to minimise risk and maximise the likelihood of achieving the pharyngitis endpoint
The results of three human GAS pharyngeal vaccine-challenge studies from the 1970s are encouraging and reassuring GAS challenge did cause pharyngitis and was safe with all participants responding to antibiotics and none experiencing complications despite these studies using more aggressive GAS strains
The study design involves direct oropharyngeal inoculation of GAS to sequential cohorts Up to four doses will be tested from 1-3 x 105 cfumL lower than previous GAS challenge studies to a maximum of 1-3 x 108 cfumL A minimum of 20 and maximum of 80 participants will be challenged The challenge procedure aligns closely that used successfully in the 1970s GAS human challenge studies An incubation period of 36 to 72 hours is expected before onset of symptoms Participants will be intensively monitored inpatients for up to six days after challenge The primary outcome measure is GAS pharyngitis as defined by a combination of positive clinical and laboratory features All participants developing pharyngitis will be treated with antibiotics and and those without pharyngitis will also be treated after 5 days Participants will be followed as outpatients at 1 week and 1 3 and 6 months after discharge
Due to an unexpectedly very high proportion of participants developing pharyngitis at the starting dose scope for dose de-escalation was subsequently included in a protocol amendment using a dose of 1-3 x 104 cfumL
A challenge model also promises an unprecedented opportunity to use modern techniques to describe the immunobiology of GAS infection Blood and saliva samples will be collected at multiple timepoints before during and after the challenge Testing of serial samples will add a dynamic next level to the clinical foundations of the challenge model enabling in-depth comparison between participants developing pharyngitis or not and paving the way to identifying immune correlates of protection
The objective of this study is to use an observational dose-escalation inpatient trial to determine the dose of GAS administered by direct oropharyngeal inoculation required to reliably produce a pharyngitis attack rate of 60 in carefully screened healthy adult volunteers A GAS strain has been specially selected and prepared for this study to ensure safety and clinical relevance Potential participants aged 18 to 40 years the age range associated with the lowest risk of invasive GAS disease will be carefully screened to minimise risk and maximise the likelihood of achieving the pharyngitis endpoint
The results of three human GAS pharyngeal vaccine-challenge studies from the 1970s are encouraging and reassuring GAS challenge did cause pharyngitis and was safe with all participants responding to antibiotics and none experiencing complications despite these studies using more aggressive GAS strains
The study design involves direct oropharyngeal inoculation of GAS to sequential cohorts Up to four doses will be tested from 1-3 x 105 cfumL lower than previous GAS challenge studies to a maximum of 1-3 x 108 cfumL A minimum of 20 and maximum of 80 participants will be challenged The challenge procedure aligns closely that used successfully in the 1970s GAS human challenge studies An incubation period of 36 to 72 hours is expected before onset of symptoms Participants will be intensively monitored inpatients for up to six days after challenge The primary outcome measure is GAS pharyngitis as defined by a combination of positive clinical and laboratory features All participants developing pharyngitis will be treated with antibiotics and and those without pharyngitis will also be treated after 5 days Participants will be followed as outpatients at 1 week and 1 3 and 6 months after discharge
Due to an unexpectedly very high proportion of participants developing pharyngitis at the starting dose scope for dose de-escalation was subsequently included in a protocol amendment using a dose of 1-3 x 104 cfumL
A challenge model also promises an unprecedented opportunity to use modern techniques to describe the immunobiology of GAS infection Blood and saliva samples will be collected at multiple timepoints before during and after the challenge Testing of serial samples will add a dynamic next level to the clinical foundations of the challenge model enabling in-depth comparison between participants developing pharyngitis or not and paving the way to identifying immune correlates of protection
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None