COVID-19 Omicron BA.5 Subvariant Dose Finding Infection Study

NCT06478420 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: COV-CHIM02
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

A phase 1, dose-finding open label clinical infection, safety and viral detection optimization in healthy volunteers immunologically experienced against SARS-CoV-2.

Conditions

SARS-CoV-2 Infection

Keywords

Covid-19; SARS-CoV-2; Controlled human infection model; Infection study; Omicron

Outcome Measures

Primary Outcomes (2)

• Occurrence of solicited and unsolicited adverse events, including severe adverse events

  Safety and human clinical response to SARS-CoV-2 Omicron BA.5 subvariant intranasal challenge in participants who are immunologically experienced against SARS-CoV-2 will be measured by solicited and unsolicited adverse events, including severe adverse events, post viral challenge and other objective parameters such as vital signs, physical examination, smell test, spirometry, ECG, and clinical laboratory results.

  Day 180

• Selection of the optimal SARS-CoV-2 dose(s)

  The optimal dose is the dose required to induce laboratory confirmed upper respiratory tract infection in 50%-75% of immunologically experienced, healthy volunteers following intranasal challenge. Laboratory confirmed infection is defined as two or more quantifiable SARS-CoV-2 qRT-PCR from mid-turbinate or throat swab samples, at two consecutive time points starting from D2 post challenge and up to discharge from quarantine.

  Day 14 or until discharge criteria is met

Secondary Outcomes (2)

• Determination of SARS-CoV-2 viral dynamics

  Day 14 or until discharge criteria is met

• Identification of host immune responses that are associated with SARS-CoV-2 infection status and/or viral load.

  Day 180

Other Outcomes (2)

• Exploratory outcome: Identification of alternate measures of viral shedding through quantitation and detection of virus

  Day 14 or until discharge criteria is met

• Exploratory outcome: Characterisation of immune responses to SARS-CoV-2, other coronaviruses and other commonly encountered vaccine or pathogen-derived antigens through various assays

  Day 180

Study Arms (5)

Group 1A: Low dose challenge

EXPERIMENTAL

Intranasal viral challenge with 1x10\^5 TCID50 in healthy volunteers (n=5-7).

Biological: Omicron BA.5 SARS-CoV-2 challenge virus

Group 1B: Medium dose #1 challenge

EXPERIMENTAL

Intranasal viral challenge with 1x10\^6 TCID50 in healthy volunteers (n=5-7).

Biological: Omicron BA.5 SARS-CoV-2 challenge virus

Group 1C: Medium dose #2 challenge

EXPERIMENTAL

Intranasal viral challenge with 1x10\^7 TCID50 in healthy volunteers (n=5-7).

Biological: Omicron BA.5 SARS-CoV-2 challenge virus

Group 1D: High dose challenge

EXPERIMENTAL

Intranasal viral challenge with 1x10\^8 TCID50 in healthy volunteers (n=5-7).

Biological: Omicron BA.5 SARS-CoV-2 challenge virus

Group 2: Dose confirmation group

EXPERIMENTAL

Intranasal viral challenge with the dose identified from group 1A-D (n=up to 24)

Biological: Omicron BA.5 SARS-CoV-2 challenge virus

Interventions

Omicron BA.5 SARS-CoV-2 challenge virus BIOLOGICAL

The SARS-CoV-2 challenge virus strain was originally obtained from a nose/throat swab taken from a patient who developed respiratory symptoms consistent with Covid-19. All manufacturing steps are carried out in accordance with GMP by BioMARC, operating out of Colorado State University.

Group 1A: Low dose challenge; Group 1B: Medium dose #1 challenge; Group 1C: Medium dose #2 challenge; Group 1D: High dose challenge; Group 2: Dose confirmation group

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-40 years 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 screening OR evidence of prior infection with SARS-CoV-2 (Evidence will be assessed by a clinician and may include evidence of a positive PCR result, a photograph of a positive lateral flow on the volunteer's phone or anti-nucleocapsid positivity at any time).
• Body Mass Index (BMI) ≥18.5 kg/m2 and ≤28 kg/m2 at admission to the quarantine unit. The upper limit of BMI may be increased to ≤30kg/m2 at the PI's discretion, in the case of a physically fit muscular individual.

You may not qualify if:

• Willing and able to provide written informed consent for participation in the study.
• Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner or any relevant health authority.
• Allow the investigator to register volunteer details with a confidential database (The Over-volunteering Protection Service) to prevent concurrent entry into clinical studies/trials.
• Agreement to refrain from blood donation during the course of the study.
• For people of child bearing potential (POCBP): a willingness to practice continuous effective contraception (see below) from 4 weeks before admission to the quarantine unit until discharge from the quarantine unit, and negative pregnancy tests on screening (urine) and pre-enrolment admission days (urine and serum).
• 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. For people of child bearing potential (POCBP) taking the combined oral contraceptive pill, a willingness to use barrier contraception during treatment with Paxlovid and until completion of one menstrual cycle after completing Paxlovid treatment.
• Able and willing (in the investigator's opinion) to comply with all study requirements.
• No clinically relevant findings in medical history or on physical examination.
• 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 or psychiatric illness. Specifically:
• a) 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: i) Significant/severe wheeze in the past. ii) Severe respiratory illness as judged by the investigator (e.g. hospitalisation for pneumonia as an adult).
• e) Migraine with aura. Cluster headache/migraine requiring prophylactic treatment.
• f) History or evidence of autoimmune disease or known immunocompromised state of any cause.
• ii) Subjects with a history of depression of any severity within the last 2 years if the Patient Health Questionnaire-9 score is ≥4.
• h) Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following injections or venepuncture.
• i) Other major disease that, in the opinion of the Investigator, could interfere with a subject completing the study and necessary investigations.

Sponsors & Collaborators

• University of Oxford: lead
• Imperial College Healthcare NHS Trust: collaborator
• Chelsea and Westminster Hospital, UK: collaborator
• Royal Free London NHS Trust: collaborator

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

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

• Helen McShane, MD PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2024
• First Posted: June 27, 2024
• Study Start: August 8, 2024
• Primary Completion (Estimated): October 31, 2028
• Study Completion (Estimated): October 31, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)