Development of a Controlled Human Infection Model for Assessment of SARS-CoV-2 Omicron Subvariants
COVHIC003
1 other identifier
interventional
38
0 countries
N/A
Brief Summary
COVHIC003 is a human infection challenge study in which healthy adults aged 18-50 previously vaccinated with an approved COVID-19 vaccine will be administered a SARS-CoV-2 Omicron EG.5.1 variant given by drops in the nose. The aim is to achieve breakthrough upper-respiratory infection in a proportion of volunteers with mild or no illness, providing information on the course of Omicron infection and the immune response in vaccinated people. This study will establish an optimised challenge dose and model that can then be used to evaluate new vaccines and treatments in follow-on trials. Participants will stay in a quarantine unit for approximately 10-12 days, depending on infection status, and will be closely monitored with regular swabs, blood tests and symptom assessments throughout their stay. They will be followed up by the study team for 6 months after being discharged. This study is sponsored by Imperial College London and forms part of the MUSICC project which is led by Imperial College London and co-funded by the European Union's Horizon Europe Programme and the Coalition for Epidemic Preparedness Innovations (CEPI). Quarantine will take place at specialist facilities in Oxford or at the Royal Free Hospital in London.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2026
Typical duration for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 28, 2026
CompletedFirst Posted
Study publicly available on registry
February 9, 2026
CompletedStudy Start
First participant enrolled
June 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2027
Study Completion
Last participant's last visit for all outcomes
December 31, 2028
February 9, 2026
February 1, 2026
1.6 years
January 28, 2026
February 4, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria.
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria. To assess safety and human clinical response to SARS-CoV-2 Omicron EG.5.1 intranasal challenge in both previously infected (unvaccinated or vaccinated) and uninfected vaccinated volunteers. To evaluate the safety of Omicron variant SARS-CoV-2 challenge in healthy participants, by assessing: • Occurrence of AEs within 28 days post-viral challenge (Day 0 to Day 28)
28 Days
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria.
To assess the safety of a GMP SARS-CoV-2 EG.5.1 variant challenge virus in vaccinated healthy adult volunteers with or without previous infection and establish the attack rate (target 50-70%) with optimised dose and screening criteria. To assess safety and human clinical response to SARS-CoV-2 Omicron EG.5.1 intranasal challenge in both previously infected (unvaccinated or vaccinated) and uninfected vaccinated volunteers To evaluate the safety of Omicron variant SARS-CoV-2 challenge in healthy participants, by assessing: • • Occurrence of SAEs related to the viral challenge (Day 0 to Day 180)
180 Days
Selection of the SARS-CoV-2 Omicron EG.5.1 dose(s) required to induce upper respiratory tract infection in 50-75% of previously SARS-CoV-2 infected and uninfected vaccinated volunteers (vaccinated or unvaccinated) healthy volunteers following intranasal
Selection of the SARS-CoV-2 Omicron EG.5.1 dose(s) required to induce upper respiratory tract infection in 50-75% of previously SARS-CoV-2 infected and uninfected vaccinated volunteers (vaccinated or unvaccinated) healthy volunteers following intranasal challenge. Laboratory confirmed infection is defined as: two quantifiable (≥LLOQ) RT-PCR measurements from mid turbinate or throat samples, reported on 2 or more consecutive timepoints, starting from Day 2 (inclusive) post-inoculation and up to discharge from quarantine (Day 8 for uninfected participants or Day 10 for infected participants)
10 Days
Study Arms (4)
Group 1a: SARS-CoV-2 Omicron EG.5.1
EXPERIMENTALStarting dose 10\^5 TCID50, vaccinated, pre-selection for low serum antibodies, n = up to 12
Group 1b: SARS-CoV-2 Omicron EG.5.1
EXPERIMENTALDose escalate: 10\^6 TCID50, vaccinated, pre-selection for low serum antibodies, n = up to 12
Group 1c: SARS-CoV-2 Omicron EG.5.1
EXPERIMENTALDose de-escalate: 10\^4 TCID50, vaccinated, pre-selection for low serum antibodies, n = up to 12
Group 2: SARS-CoV-2 Omicron EG.5.1
EXPERIMENTAL10\^6 TCID50 with multiple doses and/or lower sero-screening threshold
Interventions
10\^5 TCID50 This is a SARS-CoV-2 Omicron EG.5.1 challenge agent which has not been given in controlled human infection studies previously.
10\^6 TCID50 This is a SARS-CoV-2 Omicron EG.5.1 challenge agent which has not been given in controlled human infection studies previously
10\^4 TCID50 This is a SARS-CoV-2 Omicron EG.5.1 challenge agent which has not been given in controlled human infection studies previously
Eligibility Criteria
You may qualify if:
- The study informed consent form has been signed and dated by the participant and the Investigator
- Adults age between 18 and 50 years inclusive (at the time of enrolment)
- Evidence of having had at least one COVID-19 vaccine, with the last vaccination at least 3 months before enrolment
- Positive serology for SARS-CoV-2 at (pre)screening
- Sero-suitable as defined by having serum and/or nasal antibody titres less than a pre-defined cut-off of a defined assay(s) which will be specified in a separate SOP and based on accumulating antibody data
- People of child-bearing potential (POCBP) must be willing and able to use contraception as described in the study protocol from 2 weeks before the scheduled date of viral challenge until the end discharge from quarantine.
- 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
- 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 until the end of quarantine
- Agree to abstain from sexual activity or use effective contraception from the start of treatment with Paxlovid until 7 days after completing treatment with Paxlovid should they receive it
You may not qualify if:
- Participants will have a documented medical history either prior to entering the study and/or following medical history review with the study physician at screening
- Willing to be registered with The Over-Volunteering Protection Service (TOPS)
- 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
- 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 Investigator
- Significant history or presence of drug or alcohol misuse (exceeding \>28 units a week)
- Current use of any drugs taken through the nasal or inhaled route including recreational drugs
- Psychiatric illness including participants with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis.
- Current active smokers, equivalent to \>5 cigarettes per week, including use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch) or electronic cigarettes. • Participants who have smoked ≥5 pack years at any time \[5 pack years is equivalent to one pack of 20 cigarettes a day for 5 years\]) or the equivalent amount of nicotine if using alternative forms. • Ex-smokers who have smoked \<5 pack years at any time must not of have regularly smoked in the last 3 months equivalent to \>5 cigarettes per week.
- Family history of 1st degree relative aged 50 years or less with sudden cardiac or unexplained death
- Personal or Family History of unexpectedly severe COVID-19, adverse response to any other viral disease e.g. Guillain-Barré, or a family history (described as a 1st degree relative) with clotting disorders
- A total body weight of ≤ 45kg and a Body Mass Index (BMI) ≤18 kg/m2 and ≥28 kg/m2. The upper limit of BMI may be increased to ≤ 30kg/m2 at the Investigator's discretion, in the case of physically fit muscular individual
- Venous access deemed inadequate for the phlebotomy demands of the study.
- Any clinically significant abnormal finding on screening biochemistry, haematology and microbiology blood tests or urinalysis i.e. grade 1 lab abnormalities or above apart from minor deviations which are clinically acceptable and approved by the Investigator
- +28 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Christopher Chiu, BMBCh FRCP FRCPath PhD
Imperial College London
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- BASIC SCIENCE
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 28, 2026
First Posted
February 9, 2026
Study Start (Estimated)
June 1, 2026
Primary Completion (Estimated)
December 31, 2027
Study Completion (Estimated)
December 31, 2028
Last Updated
February 9, 2026
Record last verified: 2026-02