Singapore SARS-CoV-2 Human Challenge Study

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

Status

Active, not recruiting

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06654973

Acronym

Sing-CoV

Enrollment

Registered

2024-10-23

Start date

2024-08-27

Completion date

2026-12-31

Last updated

2026-01-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

COVID 19

Keywords

SARS-CoV-2, Human challenge study, Delta variant, Correlates of protection, Determinants of breakthrough infection

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.

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.

Interventions

OTHERGMP-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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

21 Years to 30 Years

Healthy volunteers

Yes

Inclusion criteria

1. An informed consent form (ICF) has been signed and dated by the participant, an investigator, and a witness 2. Adults age between 21 and 30 years inclusive (at the time of consent) 3. Evidence of having had a complete primary COVID-19 vaccination course as recommended by the Ministry of Health\*, with the last vaccination at least 14 days before enrolment 4. Sero-suitable based on the pre-screening serology result 5a) Female participants must be willing and able to use contraception from 2 weeks before the scheduled date of viral challenge until 6 months after receipt of the final dose of study virus. Negative urine pregnancy tests will be required at screening, and on admission to the quarantine unit a negative serum beta human chorionic gonadotropin (β-hCG) is required prior to inoculation. 5b) Male participants who are willing to use one of the contraception methods described in the study protocol, from the time of the date of viral challenge, for 6 months. 6\) In good health with no history of clinically significant medical conditions (as described in

Exclusion criteria

) that would interfere with subject safety, as defined by medical history, physical examination and routine laboratory tests, ECG, and Chest X-Ray and determined by the Investigator at an admission evaluation. 7\) Willing and able to commit to participation in the study.

Design outcomes

Primary

Measure	Time frame	Description
To identify a safe dose of SARS-CoV-2 in healthy volunteers in Singapore, suitable for future intervention studies	From day of viral challenge (Day 0) to Day 28 follow-up visit	To evaluate the safety of a SARS-CoV-2 challenge in healthy participants by assessing: * Occurrence of unsolicited AEs post-viral challenge (Day 0) up to the Day 28 follow up visit. * Occurrence of SAEs related to the viral challenge from the viral challenge (Day 0) up to the Day 28 follow up visit.
To identify an infectious dose of SARS-CoV-2 in healthy volunteers in Singapore, suitable for future intervention studies	From day 2 post-inoculation to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To determine the attack rate of the Delta variant SARS-CoV-2 inoculum dose of TID 1x106 in sero-selected participants. Laboratory confirmed infection is defined as: • Two quantifiable greater than lower limit of quantification (≥LLOQ) RT-PCR measurements from mid turbinate and/or throat samples, reported on 2 or more consecutive timepoints, starting from Day 2 post-inoculation and up to discharge from quarantine.

Secondary

Measure	Time frame	Description
To assess the SARS-CoV-2 viral dynamics in upper respiratory samples in healthy volunteers	Day of inoculation (Day 0) to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To assess viral dynamics using a) mid turbinate samples, and b) throat swabs, as measured by qPCR.
To further assess SARS-CoV-2 viral infection rates in upper respiratory samples in healthy volunteers	From day of viral challenge (Day 0) to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To assess the incidence of laboratory confirmed infection rates using a) mid turbinate samples, b) throat swabs, and c) both mid turbinate and throat swabs.
To assess the incidence of SARS-CoV-2 illness, in healthy volunteers	Day of inoculation (Day 0) to discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	The incidence of: * Upper Respiratory Tract illness (URTI) * Lower Respiratory Tract illness (LRTI) * Systemic illness (SI) * Febrile illness (FI) * Proportion of participants with Grade 3 symptoms on any occasion at any time from the last assessment on Day 0 to discharge from quarantine * Proportion of participants with Grade 2 or higher symptoms on any occasion at any time from the last assessment on Day 0 to discharge from quarantine * Proportion of participants with Grade 2 or higher Symptoms on two separate occasions at any time from the last assessment on Day 0 to discharge from quarantine * Proportion of participants with any symptom (grade \>=1) on any occasion at any time from the last assessment on Day 0 to discharge from quarantine * Proportion of participants with any symptom (grade \>=1) on two separate occasions at any time from the last assessment on Day 0 to discharge from quarantine
To assess SARS-CoV-2 induced symptoms, in healthy volunteers	Day of inoculation (Day 0) to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	Sum total symptoms diary card score: sum total clinical symptoms (TSS) as measured by graded symptom scoring system, starting one day post-viral challenge (Day 1) up to discharge from quarantine.
To assess the incidence of symptomatic SARS-CoV-2 infection, in healthy volunteers	From day of viral challenge (Day 0) to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To assess the incidence of lab-confirmed symptomatic SARSCoV-2 infection using a) mid turbinate samples, b) throat swabs, and c) both mid turbinate and throat swabs.

Other

Measure	Time frame	Description
To explore the changes in cellular immunity after SARS-CoV-2 challenge	Up to Day 360 post-inoculation	Assays performed on blood, stool and mucosal samples include cellular cell quantification and quality of immunity (for example T and B cell frequencies, phenotypes, and functionality assays, ELISPOTs, ICS).
To explore the transcriptomic changes after SARS-CoV-2 challenge	Up to Day 360 post-inoculation	Assays performed on blood, stool and mucosal samples to measure transcriptome levels and changes (for example, RNAseq, single cell RNAseq, microarray, PCR)
To explore the changes in smell (anosmia/parosmia) through infection.	Day of inoculation (Day 0) to Day 28 follow up	The University of Pennslvania Smell Identification Test (UPSIT) will be used. It is provided as booklets containing a series of cards that the participants scratch and smell then asked to identify the odours. The test provides an index of absolute dysfunction (ie, anosmia, severe microsmia, moderate microsmia, mild microsmia, normosmia, factitious), as well as relative dysfunction based upon age and gender-adjusted normative percentile ranks. The total number of odorant stimuli out of 40 that is correctly identified serves as the test measure. Scores on this test correlate well with other types of olfactory tests, including threshold tests. The UPSIT is designed to be self-administered after explanation of the test by study staff and will be performed once before virus inoculation and then approximately every third day starting from Day 1, though the test can be conducted more frequently at the discretion of the Investigator.
To explore changes in the vasculature during SARS-CoV-2 infection in healthy adults	Up to Day 360 post-inoculation	To measure changes in endothelial function during SARS-CoV-2 infection: • To assess levels of endothelial derived mediators (e.g., prostacyclin, endothelin-1, nitric oxide) in the plasma
To explore the performance of antigen rapid tests (ART) during SARS-CoV-2 infection of healthy adults	Day of admission (Day -1) to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To explore the performance of antigen rapid tests performed by participants themselves following manufacturer's instructions (no additional training) in comparison with SARS-CoV-2 PCR and culture
To explore environmental contamination in the SARS-CoV-2 human challenge model in healthy adults	Day of admission (Day -1) to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	Air samples, exhaled breath samples with the use of a face mask or G-II exhaled breath collector, and surface swab samples will be used for virus detection and quantification.
To explore the safety of a SARS-CoV-2 human challenge model in healthy adults	Day of inoculation (Day 0) to Day 28 follow up	To explore safety related measures of SARS-CoV-2 challenge in healthy participants by assessing the occurrence of haematological and biochemical laboratory abnormalities during the quarantine period.
To explore the SARS-CoV-2 viral infection rates in saliva in healthy volunteers	From Day 2 post-inoculation to discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To measure the laboratory confirmed infection rates, as defined by: * Occurrence of at least two quantifiable (≥LLOQ) qPCR measurements, reported on 2 or more consecutive time points, starting from Day 2 post-inoculation and up to discharge from quarantine. * Occurrence of at least two detectable (≥LLOD) qPCR measurements, reported on 2 or more consecutive time points, starting from Day 2 post-inoculation and up to discharge from quarantine. * Occurrence of at least one quantifiable (≥LLOQ) SARS-CoV-2 viral cell culture measurement, starting from Day 2 post-inoculation and up to discharge from quarantine.
To explore the SARS-CoV-2 viral dynamics in saliva in healthy volunteers	From Day 1 post-inoculation up to discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To assess viral dynamics in saliva by qPCR.
To explore SARS-CoV-2 viral infection in stool of healthy volunteers	From Day 1 post-inoculation up to discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)	To measure SARS-CoV-2 excretion in the stool by: • Virus detection and quantification using qRT-PCR
To explore the changes in humoral immunity after SARS-CoV-2 challenge	Up to Day 360 post-inoculation	Assays performed on blood, stool and mucosal samples to assess humoral immunity / systems serology SARS-CoV-2 (for example: SARS-CoV-2 neutralizing titres, ELISAs to IgG, IgM, IgA, sIgA, ADCC)
To explore the proteomic changes after SARS-CoV-2 challenge	Up to Day 360 post-inoculation	Assays performed on blood, stool and mucosal samples to assess proteomic levels and changes (for example, cytokine and chemokines).

Countries

Singapore

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026