COV-CHIM01: SARS-CoV-2 (COVID-19) Dose Finding Infection Study

NCT04864548 | Unknown Phase 1 DMC

• 1 other identifier: COV-CHIM01
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 3

Brief Summary

A phase I, experimental dose finding, open label, clinical infection, safety and viral detection optimisation in previously SARS-CoV-2 infected (unvaccinated or vaccinated) or uninfected vaccinated volunteers.

Conditions

Coronavirus

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Occurrence of solicited and unsolicited adverse events

  To assess safety and human clinical response to wild type SARS-CoV-2 intranasal challenge in both previously SARS- CoV-2 infected (unvaccinated or vaccinated) and uninfected vaccinated participants via occurrence of adverse events (solicited and unsolicited) collected in e-diaries

  Day 84

• Occurrence of adverse events as determined by medical assessment

  Collection of AE data at each visit time point after SARS-CoV-2 inoculation (Graded 0-3)

  Day 365

• Selection of optimal dose(s)

  The SARS-CoV-2 dose required to induce upper respiratory tract infection in 50% (+/-10%) of previously SARS-CoV-2 infected healthy volunteers following intranasal challenge. Defined by laboratory identification of SARS-CoV-2 from nasal and pharyngeal swab, using qPCR and/or quantitative live viral detection at two consecutive 12- hourly time points starting 24 hours post-inoculation and up to discharge from quarantine. Optimal dose to be defined in previously SARS-CoV-2 infected (vaccinated or unvaccinated) and uninfected vaccinated healthy volunteers

  Day 14 or until discharge criteria is met

Secondary Outcomes (7)

• Determination of SARS-CoV-2 viral dynamics

  Day 365

• Exploratory Immunology: Identification of laboratory markers

  Day 365

• Exploratory Immunology: Identification of laboratory markers

  Day 365

• Exploratory Immunology: Identification of laboratory markers

  Day 365

• Exploratory Immunology: Identification of laboratory markers

  Day 365

Study Arms (11)

Group 1A: Low dose challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^1 TCID\_50 in previously infected volunteers N= 6-8 participants

Biological: SARS-CoV-2 virus

Group 1B: Medium dose #1 challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^2 TCID\_50 in previously infected volunteers N= 6-8 participants

Biological: SARS-CoV-2 virus

Group 1C: Medium dose #2 challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^3 TCID\_50 in previously infected volunteers N= 6-8 participants

Biological: SARS-CoV-2 virus

Group 1D: Medium dose #3 challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^4 TCID\_50 in previously infected volunteers N= 4-8 participants

Biological: SARS-CoV-2 virus

Group 1E: High dose challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^5 TCID\_50 in previously infected volunteers N= 4-8 participants

Biological: SARS-CoV-2 virus

Group 2: Safety & Dose confirmation Group

EXPERIMENTAL

Intranasal viral challenge with the dose identified from Group 1a-e (1x10\^1, 1x10\^2, 1x10\^3, 1x10\^4, or 1x10\^5 TCID\_50) N=10-30 participants

Biological: SARS-CoV-2 virus

Group 3a: Medium dose #1 challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^2 TCID\_50 in previously uninfected, vaccinated volunteers N=6-8 participants

Biological: SARS-CoV-2 virus

Group 3b: Medium dose #2 challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^3 TCID\_50 in previously uninfected, vaccinated volunteers N=4-8 participants

Biological: SARS-CoV-2 virus

Group 3c: Medium dose #3 challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^4 TCID\_50 in previously uninfected, vaccinated volunteers N=4-8 participants

Biological: SARS-CoV-2 virus

Group 3d: High dose challenge

EXPERIMENTAL

Intranasal viral challenge with 1 x 10\^5 TCID\_50 in previously uninfected, vaccinated volunteers N=4-8 participants

Biological: SARS-CoV-2 virus

Group 4: Safety & Dose confirmation Group

EXPERIMENTAL

Intranasal viral challenge with the dose identified from Group 3a-d (1x10\^2, 1x10\^3, 1x10\^4 or 1x10\^5 TCID\_50) N=10-30 participants

Biological: SARS-CoV-2 virus

Interventions

SARS-CoV-2 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. The isolate was plaque purified to obtain a 'single' virus entity. The selected plaque, B1, was subsequently manufactured in accordance with GMP at the Great Ormond Street manufacturing suite.

Group 1A: Low dose challenge; Group 1B: Medium dose #1 challenge; Group 1C: Medium dose #2 challenge; Group 1D: Medium dose #3 challenge; Group 1E: High dose challenge; Group 2: Safety & Dose confirmation Group; Group 3a: Medium dose #1 challenge; Group 3b: Medium dose #2 challenge; Group 3c: Medium dose #3 challenge; Group 3d: High dose challenge; Group 4: Safety & Dose confirmation Group

Eligibility Criteria

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

You may qualify if:

• Aged 18-30 years on proposed date of enrolment.
• Body Mass Index (BMI) ≥18.5 kg/m2and ≤28 kg/m2.

You may not qualify if:

• Volunteer is willing and able to give 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 Prevention Service) to prevent concurrent entry into clinical studies/trials
• Agreement to refrain from blood donation during the course of the study
• a. For women of child bearing potential (WOCBP), a willingness to practice continuous effective contraception during the study and, a negative pregnancy test on the day(s) of screening and challenge b. b. For women of child bearing potential (WOCBP) taking the combined oral contraceptive pill, a willingness to use barrier contraception with spermicide during treatment with Paxlovid and for 30 days after completing Paxlovid treatment (should they receive it).
• 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 in the opinion of a clinically qualified investigator, in discussion with the CI if needed
• For Groups 1 \& 2: Previous microbiological confirmation of SARS-CoV-2 infection \> 3 months prior to enrolment (Proof of positive PCR or lateral flow antigen test confirmed via medical notes/ or UK HSA or a history from a volunteer consistent with SARS-CoV-2 infection with other evidence of this infection such as a photograph of a positive lateral flow test on the volunteer's phone or similar) OR serological confirmation such as positive anti-nucleocapsid IgG serology (unless this is explainable by prior vaccination) with the most recent history of symptoms or exposure likely to represent SARS-CoV-2 infection having occurred \> 3 months prior to enrolment.
• For Groups 3 \& 4: Written or electronic evidence of at least one vaccination against SARS- CoV-2 \>21 days prior to enrolment (proof required would include written or electronic evidence from GP/ medical records or electronic NHS COVID pass) where no history of symptoms or exposure can be identified to determine the timing of SARS-CoV-2 infection, volunteers may be enrolled \>7 weeks from the identification of anti-nucleocapsid positivity and \>3 months from their last negative anti-nucleocapsid antibody test.
• \) History or evidence of any clinically significant or currently active cardiovascular, (including thromboembolic events), respiratory (excluding SARS CoV-2 infection), dermatological, gastrointestinal, endocrine, haematological, hepatic, immunological, rheumatological, metabolic, urological, renal, neurological or psychiatric illness. Specifically:
• Volunteers 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) Clinically significant respiratory symptoms including wheeze which has ever resulted in hospitalisation iii) Known bronchial hyper reactivity to viruses
• History of thromboembolic, cardiovascular or cerebrovascular disease
• History or evidence of diabetes mellitus (Type I or Type II)
• Migraine with associated neurological symptoms such as hemiplegia or vision loss. Cluster headache/migraine or prophylactic treatment for migraine

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (3)

Oxford Clinical Research Facility (OxCRF)

Oxford, Oxon, OX3 7LE, United Kingdom

RECRUITING

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxon, OX3 7LJ, United Kingdom

RECRUITING

Oxford University Hospital NHS Trust

Oxford, Oxon, OX3 9DU, United Kingdom

RECRUITING

Related Publications (1)

• Jackson S, Marshall JL, Mawer A, Lopez-Ramon R, Harris SA, Satti I, Hughes E, Preston-Jones H, Cabrera Puig I, Longet S, Tipton T, Laidlaw S, Doherty RP, Morrison H, Mitchell R, Tanner R, Ateere A, Stylianou E, Wu MS, Fredsgaard-Jones TPW, Breuer J, Rapeport G, Ferreira VM, Gleeson F, Pollard AJ, Carroll M, Catchpole A, Chiu C, McShane H; COV-CHIM01 study team. Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study. Lancet Microbe. 2024 Jul;5(7):655-668. doi: 10.1016/S2666-5247(24)00025-9. Epub 2024 May 1.

  PMID: 38703782 DERIVED

MeSH Terms

Conditions

Coronavirus Infections; COVID-19

Condition Hierarchy (Ancestors)

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

Study Officials

• Helen McShane, MD and PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Volunteer Recruitment Co-ordinator

CONTACT

07990431010; Covid19-challenge@paediatrics.ox.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This is an open-label trial, however in order to minimise volunteer adverse event reporting bias by volunteers, study participants will be kept blinded to swab results for as long as possible.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 29, 2021
• Study Start: May 27, 2021
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: January 6, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3)