Ignite Creation Date:
2024-10-26 @ 3:43 PM
Last Modification Date:
2024-10-26 @ 3:43 PM
Study NCT ID:
NCT06654973
Status:
RECRUITING
Last Update Posted:
None
First Post:
2024-10-09
Brief Title:
Singapore SARS-CoV-2 Human Challenge Study
Sponsor:
None
Organization:
None
Study Overview
Official Title:
The Singapore Platform for Controlled Human Infections With SARS-CoV-2
Status:
RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Sing-CoV
Brief Summary:
The goal of this study is to conduct a safe SARS-CoV-2 Delta variant human infection challenge in adult healthy volunteers The main objectives are to
Induce laboratory confirmed infection in up to 70 of participants
Confirm the safety profile as measured by the occurrence of adverse events AEs and serious adverse events SAEs from the day of viral challenge Day 0 up to Day 28 follow-up
Participants will be given the GMP-produced Delta SARS-CoV-2 virus via intranasal drops using the optimized conditions established in the Development of a SARS-CoV-2 Delta variant human infection challenge model COVHIC002 Human Challenge Study being conducted in the UK A safe and well-tolerated human challenge model with the SARS-CoV-2 Delta variant will be established in Singapore This model will be used to accelerate next-generation vaccine development and to determine the factors associated with altered clinical and virological outcomes correlates of protection and targets for the development of novel vaccines therapeutics and diagnostics
Induce laboratory confirmed infection in up to 70 of participants
Confirm the safety profile as measured by the occurrence of adverse events AEs and serious adverse events SAEs from the day of viral challenge Day 0 up to Day 28 follow-up
Participants will be given the GMP-produced Delta SARS-CoV-2 virus via intranasal drops using the optimized conditions established in the Development of a SARS-CoV-2 Delta variant human infection challenge model COVHIC002 Human Challenge Study being conducted in the UK A safe and well-tolerated human challenge model with the SARS-CoV-2 Delta variant will be established in Singapore This model will be used to accelerate next-generation vaccine development and to determine the factors associated with altered clinical and virological outcomes correlates of protection and targets for the development of novel vaccines therapeutics and diagnostics
Detailed Description:
Human challenge studies involve the deliberate infection of volunteers to allow detailed investigation of host-pathogen interactions and the effect of interventions The strength of these studies lies in their highly controlled nature Carefully selected participant groups are inoculated with standardised amounts of a well-characterised virus This enables exact longitudinal measurement of viral kinetics immunological responses transmission dynamics and the duration of infectious shedding By giving all study participants the same virus at the same dose and under the same conditions confounding by virus strain dose and exposure is controlled Host factors associated with inter-individual differences in clinical outcome as well as the effect of interventions can then be robustly inferred
The Human Challenge study contrasts with even the most well-controlled field trials including household contact studies In natural infection the virus quasi-species ie mixture of slightly differing virus particles dose timing and conditions of exposure cannot be known and contacts are only identified following diagnosis of the index case At this time secondary exposure has almost always already occurred thus missing transmission events as well as the early phase of infection Human challenge is therefore the only study design where the earliest pre-symptomatic changes post infection may be studied These early time-points are critical to understanding how some people who are exposed to a virus resist infection and to delineate early infectiousness and transmissibility
The first SARS-CoV-2 human challenge study COVHIC001 was conducted in 2021 and showed no serious safety concerns after inoculating 36 healthy unvaccinated young adults with a pre-Alpha Wuhan strain of SARS-CoV-2 A follow up human challenge study with a Delta variant COVHIC002 is currently ongoing in the UK COVHIC002 will determine and optimise the conditions for a safe human challenge model with the SARS-CoV-2 Delta variant These conditions will subsequently be applied in this companion study Sing-CoV
Importantly a model of vaccine breakthrough infection will have a substantially improved safety profile compared with the first seronegative study as
1 The risk of severe disease and protracted symptoms among healthy volunteers are substantially reduced by vaccination
2 Highly effective anti-virals are available as rescue therapy
3 Data from the SARS-CoV-2 human challenge studies both COVHIC001 and COVHIC002 underpin the design of the Sing-CoV study and supports robust informed consent
Recent SARS-CoV-2 variants-of-concern VOC Delta and Omicron have shown high rates of vaccine breakthrough infection indicating that human challenge with these strains may be optimised as a platform for the rapid testing of vaccines and therapeutics in small numbers of participants despite pre-existing immunity especially between waves of the pandemic when occurrence of natural disease is relatively uncommon This will enable efficient early-stage testing of the many vaccine and antiviral candidates in development so that the most promising can go forward quickly enough to large-scale field efficacy trials to meaningfully tackle the ongoing pandemic
Thus in the short term a Delta human challenge model will uniquely enable
1 A model of breakthrough infection that can be used to assess transmission blocking potential of new vaccines and treatments
2 Identification of the immune factors associated with susceptibility to breakthrough infection
3 Studies that can uniquely provide proof-of-principle efficacy data for vaccine candidates that confer cross-strain protection
Establishing the capability to perform SARS-CoV-2 human challenge studies in Singapore will be highly significant Firstly this will facilitate development of therapeutics and vaccines in the region secondly it will ensure inferences drawn from SARS-CoV-2 human challenge studies are applicable to people of Asian ethnicity and thirdly it will support capacity development in the region where future coronavirus pandemics like SARS-CoV-1 and SARS-CoV-2 are expected to originate
The Human Challenge study contrasts with even the most well-controlled field trials including household contact studies In natural infection the virus quasi-species ie mixture of slightly differing virus particles dose timing and conditions of exposure cannot be known and contacts are only identified following diagnosis of the index case At this time secondary exposure has almost always already occurred thus missing transmission events as well as the early phase of infection Human challenge is therefore the only study design where the earliest pre-symptomatic changes post infection may be studied These early time-points are critical to understanding how some people who are exposed to a virus resist infection and to delineate early infectiousness and transmissibility
The first SARS-CoV-2 human challenge study COVHIC001 was conducted in 2021 and showed no serious safety concerns after inoculating 36 healthy unvaccinated young adults with a pre-Alpha Wuhan strain of SARS-CoV-2 A follow up human challenge study with a Delta variant COVHIC002 is currently ongoing in the UK COVHIC002 will determine and optimise the conditions for a safe human challenge model with the SARS-CoV-2 Delta variant These conditions will subsequently be applied in this companion study Sing-CoV
Importantly a model of vaccine breakthrough infection will have a substantially improved safety profile compared with the first seronegative study as
1 The risk of severe disease and protracted symptoms among healthy volunteers are substantially reduced by vaccination
2 Highly effective anti-virals are available as rescue therapy
3 Data from the SARS-CoV-2 human challenge studies both COVHIC001 and COVHIC002 underpin the design of the Sing-CoV study and supports robust informed consent
Recent SARS-CoV-2 variants-of-concern VOC Delta and Omicron have shown high rates of vaccine breakthrough infection indicating that human challenge with these strains may be optimised as a platform for the rapid testing of vaccines and therapeutics in small numbers of participants despite pre-existing immunity especially between waves of the pandemic when occurrence of natural disease is relatively uncommon This will enable efficient early-stage testing of the many vaccine and antiviral candidates in development so that the most promising can go forward quickly enough to large-scale field efficacy trials to meaningfully tackle the ongoing pandemic
Thus in the short term a Delta human challenge model will uniquely enable
1 A model of breakthrough infection that can be used to assess transmission blocking potential of new vaccines and treatments
2 Identification of the immune factors associated with susceptibility to breakthrough infection
3 Studies that can uniquely provide proof-of-principle efficacy data for vaccine candidates that confer cross-strain protection
Establishing the capability to perform SARS-CoV-2 human challenge studies in Singapore will be highly significant Firstly this will facilitate development of therapeutics and vaccines in the region secondly it will ensure inferences drawn from SARS-CoV-2 human challenge studies are applicable to people of Asian ethnicity and thirdly it will support capacity development in the region where future coronavirus pandemics like SARS-CoV-1 and SARS-CoV-2 are expected to originate
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None