SARS-CoV-2 Human Challenge Characterisation Study

NCT04865237 | Completed Results DMC

• 1 other identifier: 20IC6437
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

This is a dose optimisation study in healthy adults aged 18-30 who will be experimentally inoculated with SARS-CoV-2. The aim is to cause PCR-confirmed upper respiratory infection in the majority of challenged individuals with minimal or no illness, providing data on the course of COVID-19 and the immune response to SARS-CoV-2 infection. This will establish an optimised dose and study design that will then be used to evaluate the efficacy of treatment and vaccine candidates plus level and duration of immune protection in follow-on trials.

Conditions

COVID-19; SARS-CoV Infection; Corona Virus Infection; Coronavirus

Outcome Measures

Primary Outcomes (3)

• Number of Unsolicited Adverse Events in Healthy Participants Challenged With Wild Type SARS-CoV-2

  To evaluate the safety of wild type SARS-CoV-2 challenge in healthy participants by assessing occurrence of unsolicited AEs within 30 days post-viral challenge (Day 0) up to Day 28 follow up.

  Day 0 to 28 (28 days)

• Number of SAEs Related to Viral Challenge

  To evaluate the safety of wild type SARS-CoV-2 challenge in healthy participants by assessing occurrence of SAEs related to the viral challenge from the viral challenge (Day 0) up to Day 28 follow up.

  Day 0 to 28 (28 days)

• Number of Participants With Laboratory Confirmed Infections

  To identify a SARS-Cov-2 inoculum dose that safely induces laboratory confirmed infection in ≥50% of participants (ideally between 50% and 70%). 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 24 hours post-inoculation and up to discharge from quarantine.

  From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

Secondary Outcomes (12)

• Number of Patients With Laboratory Confirmed Infections by Mid-turbinate and/or Throat Swabs

  From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

• Number of Symptomatic SARS-Cov-2 Infected Participants

  From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

• SARS-CoV-2 Viral Dynamics (VL-AUC) in Upper Respiratory Samples in Healthy Volunteers

  From 24 hours post-inoculation to 312 hours post-inoculation

• SARS-CoV-2 Induced Symptoms in Healthy Volunteers by the Mean Sum Total Symptom Score

  From 24 hours post-inoculation until discharged from Quarantine, up to a maximum period of 16 days

• Number of Participants With Incidence of SARS-CoV-2 Illness in Healthy Volunteers

  Day 0 to discharge from Quarantine, up to a maximum of 17 days

Other Outcomes (4)

• Average Change in Smell Measured by the University of Pennsylvania Smell Identification Test (UPSIT)

  Day 0 to 28 (28 days)

• Average Pulmonary Changes Measured by Spirometry (FEV1, FVC)

  Day 0 to 28 (28 days)

• Number of Haematological and Biochemical Laboratory Abnormalities During the Quarantine Period

  Day 0 to 28 (28 days)

Study Arms (3)

Healthy Volunteers Dose Level 1

EXPERIMENTAL

Dose Level 1: SARS-CoV-2, intranasally (10\^1 TCID50 dose)

Biological: SARS-CoV-2 Virus 1x10^1 TCID50; Drug: Remdesivir

Healthy Volunteers Dose Level 2

EXPERIMENTAL

Dose Level 2: SARS-CoV-2, intranasally (10\^2 TCID50 dose)

Drug: Remdesivir; Biological: SARS-CoV-2 Virus 1x10^2 TCID50

Healthy Volunteers Dose Level 3

EXPERIMENTAL

Dose Level 3: SARS-CoV-2, intranasally (10\^3 TCID50 dose)

Drug: Remdesivir; Biological: SARS-CoV-2 Virus 1x10^3 TCID50

Interventions

SARS-CoV-2 Virus 1x10^1 TCID50 BIOLOGICAL

SARS-CoV-2, intranasally, (1x10\^1 TCID50)

Healthy Volunteers Dose Level 1

Remdesivir DRUG

VEKLURY™

Also known as: VEKLURY™

Healthy Volunteers Dose Level 1; Healthy Volunteers Dose Level 2; Healthy Volunteers Dose Level 3

SARS-CoV-2 Virus 1x10^2 TCID50 BIOLOGICAL

SARS-CoV-2, intranasally, (1x10\^2 TCID50)

Healthy Volunteers Dose Level 2

SARS-CoV-2 Virus 1x10^3 TCID50 BIOLOGICAL

SARS-CoV-2, intranasally, (1x10\^3 TCID50)

Healthy Volunteers Dose Level 3

Eligibility Criteria

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

You may qualify if:

• An informed consent document signed and dated by the participant and the Investigator.
• Male or female, age between 18 and 30 years inclusive (at the time of consent)
• Seronegative to the challenge virus SARS-CoV-2, no history of SARS-CoV-2 infection and no previous participation in a SARS-CoV-2 vaccine trial.
• Female participants with a documented menstrual period within 28 days before the inoculation (unless using a contraceptive method that suppressed menstruation as indicated in the study protocol) and willing and able to use contraception as described in the study protocol from 2 weeks before the scheduled date of viral challenge until 90 days after receipt of the final dose of rescue medication. Negative urine pregnancy tests will be required at screening and on day 0 prior to inoculation. On admission to the quarantine unit a Negative serum beta human chorionic gonadotropin (β-hCG) is required.
• Contraceptive requirements:
• Established use of hormonal methods of contraception described below (for 2 weeks prior to the first study visit). When hormonal methods of contraception are used, male partners are required to use a condom with a spermicide:
• combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: i. oral ii. intravaginal iii. transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation: i. oral ii. injectable iii. implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal ligation
• Male sterilisation (with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate) where the vasectomised male is the sole partner for that woman.
• True abstinence - sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
• Men who are willing to use one of the contraception methods described in the study protocol, from the time of the date of viral challenge, until 90 days after receipt of the final dose of study medication.
• Contraceptive requirements:

You may not qualify if:

• Subjects will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening 8 Using the QCOVID tool, an absolute risk of COVID-associated death of 1 in 250,000 (0.0004%) or less and COVID-associated hospital admission of 1 in 5000 (0.02%) or less, unless deemed unnecessary by the CI and PI with advice from the DSMB following a formal interim assessment (see below) 9 Willing and able to commit to participation in the study
• Any potential subject who meet any of the criteria below will be excluded from participating in this study.
• Clinical history
• 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:
• Subjects 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 subject completing the study and necessary investigations.
• Immunosuppression of any type
• 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.

Sponsors & Collaborators

• Imperial College London: lead
• Hvivo: collaborator
• Royal Free Hospital NHS Foundation Trust: collaborator

Study Sites (2)

hVIVO Services Ltd, QMB Bioenterprise building

London, E1 2AX, United Kingdom

Location

Royal Free Foundation Hospital

London, United Kingdom

Location

Related Publications (4)

• 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 RESULT

• Wagstaffe HR, Thwaites RS, Sidhu JK, Lindeboom RGH, Kretschmer L, Worlock KB, Dratva LM, Huang A, Ascough S, Papargyris L, McKendry R, Collins AM, Xu J, Lemm NM, Killingley B, Kalinova M, Mann A, Catchpole A, Swadling L, Tsang JS, Maini MK, Noursadeghi M, Nikolic MZ, Teichmann SA, Openshaw PJM, Chiu C. Pre-existing and early cellular immune factors correlate with functionally complete protection against primary controlled human SARS-CoV-2 infection. Nat Commun. 2025 Dec 7;17(1):312. doi: 10.1038/s41467-025-67017-8.

  PMID: 41354730 DERIVED

• Trender W, Hellyer PJ, Killingley B, Kalinova M, Mann AJ, Catchpole AP, Menon D, Needham E, Thwaites R, Chiu C, Scott G, Hampshire A. Changes in memory and cognition during the SARS-CoV-2 human challenge study. EClinicalMedicine. 2024 Sep 21;76:102842. doi: 10.1016/j.eclinm.2024.102842. eCollection 2024 Oct.

  PMID: 39364271 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

COVID-19; Severe Acute Respiratory Syndrome; Coronavirus Infections

Interventions

remdesivir

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Professor Christopher Chiu
• Organization: Imperial College London

c.chiu@imperial.ac.uk

02083832301

Study Officials

• Christopher Chiu

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose Escalation

Study Record Dates

• First Submitted: April 1, 2021
• First Posted: April 29, 2021
• Study Start: March 6, 2021
• Primary Completion: July 11, 2022
• Study Completion: July 11, 2022
• Last Updated: May 16, 2025
• Results First Posted: May 16, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2)