Singapore SARS-CoV-2 Human Challenge Study

NCT06654973 | Active Not Recruiting DMC

• 1 other identifier: 2023/00911
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID 19

Keywords

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

Outcome Measures

Primary Outcomes (2)

• To identify a safe dose of SARS-CoV-2 in healthy volunteers in Singapore, suitable for future intervention studies

  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.

  From day of viral challenge (Day 0) to Day 28 follow-up visit

• To identify an infectious dose of SARS-CoV-2 in healthy volunteers in Singapore, suitable for future intervention studies

  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.

  From day 2 post-inoculation to day of discharge from quarantine (Day 10 for uninfected participants or Day 14 for infected participants)

Secondary Outcomes (5)

• 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 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 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 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)

• 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)

Other Outcomes (12)

• To explore the changes in smell (anosmia/parosmia) through infection.

  Day of inoculation (Day 0) to Day 28 follow up

• 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 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)

Study Arms (1)

SARS-CoV-2 Delta human infection challenge

EXPERIMENTAL

GMP-produced Delta SARS-CoV-2 virus will be given to participants via intranasal drops.

Other: GMP-produced SARS-CoV-2 Delta strain

Interventions

GMP-produced SARS-CoV-2 Delta strain OTHER

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.

SARS-CoV-2 Delta human infection challenge

Eligibility Criteria

• Age: 21 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• An informed consent form (ICF) has been signed and dated by the participant, an investigator, and a witness
• Adults age between 21 and 30 years inclusive (at the time of consent)
• 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
• 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.
• b) 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.

You may not qualify if:

• \) Willing and able to commit to participation in the study.
• History or evidence of any clinically significant or currently active cardiovascular, (including thromboembolic events), respiratory, dermatological, gastrointestinal, endocrine, haematological, hepatic, immunological, rheumatological, metabolic, urological, renal, neurological, psychiatric illness. Specifically:
• Participants with any history of physician diagnosed and/or objective test confirmed asthma, chronic obstructive pulmonary disease, pulmonary hypertension, reactive airway disease, or chronic lung condition of any aetiology or who have experienced:
• Significant/severe wheeze in the past
• Respiratory symptoms including wheeze which has ever resulted in hospitalisation
• Known bronchial hyperreactivity to viruses
• History of thromboembolic, cardiovascular or cerebrovascular disease
• History or evidence of diabetes mellitus
• Migraine with associated neurological symptoms such as hemiplegia or vision loss. Cluster headache/migraine or prophylactic treatment for migraine
• History or evidence of autoimmune disease or known immunodeficiency of any cause.
• Other major disease that, in the opinion of the Investigator, could interfere with a participant completing the study and necessary investigations.
• Any significant abnormality altering the anatomy or function of the nose or nasopharynx in a substantial way (including loss of or alterations in smell or taste), a clinically significant history of epistaxis (large nosebleeds) within the last 3 months, nasal or sinus surgery within 6 months of inoculation.
• History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
• Significant history or presence of drug or alcohol misuse
• Current use of any drugs taken through the nasal or inhaled route

Sponsors & Collaborators

• Tan Tock Seng Hospital: lead
• A*Star: collaborator
• Duke-NUS Graduate Medical School: collaborator

Study Sites (1)

National Centre for Infectious Diseases

Singapore, Singapore, 308442, Singapore

Location

Related Publications (2)

• Zhou J, Singanayagam A, Goonawardane N, Moshe M, Sweeney FP, Sukhova K, Killingley B, Kalinova M, Mann AJ, Catchpole AP, Barer MR, Ferguson NM, Chiu C, Barclay WS. Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study. Lancet Microbe. 2023 Aug;4(8):e579-e590. doi: 10.1016/S2666-5247(23)00101-5. Epub 2023 Jun 9.

  PMID: 37307844 BACKGROUND

• Killingley B, Mann AJ, Kalinova M, Boyers A, Goonawardane N, Zhou J, Lindsell K, Hare SS, Brown J, Frise R, Smith E, Hopkins C, Noulin N, Londt B, Wilkinson T, Harden S, McShane H, Baillet M, Gilbert A, Jacobs M, Charman C, Mande P, Nguyen-Van-Tam JS, Semple MG, Read RC, Ferguson NM, Openshaw PJ, Rapeport G, Barclay WS, Catchpole AP, Chiu C. Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults. Nat Med. 2022 May;28(5):1031-1041. doi: 10.1038/s41591-022-01780-9. Epub 2022 Mar 31.

  PMID: 35361992 BACKGROUND

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Barnaby E Young, MB BChir, PhD

  National Centre for Infectious Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Singapore Infectious Disease Clinical Research Network

Study Record Dates

• First Submitted: October 9, 2024
• First Posted: October 23, 2024
• Study Start: August 27, 2024
• Primary Completion: December 29, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)