NCT06654973

Singapore SARS-CoV-2 Human Challenge Study

The Singapore Platform for Controlled Human Infections With SARS-CoV-2

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Tan Tock Seng Hospital · Academic / Other
• Sex: All
• Age: 21 Years – 30 Years
• Healthy volunteers: Accepted

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.

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 (i.e., 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.

Conditions

• COVID 19

Interventions

Type	Name	Description
OTHER	GMP-produced SARS-CoV-2 Delta strain	The challenge virus used in Sing-CoV study is the same as that used in COVHIC002 study. It was originally obtained in mid 2021 from a nose-throat swab from an otherwise healthy young adult with mild COVID-19 in the community. The procedure for isolation, storage, preparation, and administration of challenge virus in this study (Sing-CoV and COVHIC002) is the same as used in the first SARS-CoV-2 human challenge study (COVHIC001) at Imperial College London and the same as used in the COV-CHIM01 (NCT04864548) SARS-CoV-2 human challenge study at University of Oxford.

Timeline

• Start date: 2024-08-27
• Primary completion: 2025-12-29
• Completion: 2026-12-01
• First posted: 2024-10-23
• Last updated: 2026-01-12

Locations

1 site across 1 country: Singapore