CoronavirusPhase 1NCT04864548
COV-CHIM01: SARS-CoV-2 (COVID-19) Dose Finding Infection Study
A Phase 1 study testing SARS-CoV-2 virus in people with Coronavirus, run by University of Oxford at 3 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Coronavirus
- What is being tested?
- SARS-CoV-2 virus
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 132 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- 27 May 2021to Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Aged 18-30 years on proposed date of enrolment.
- Body Mass Index (BMI) ≥18.5 kg/m2and ≤28 kg/m2.
- In good health with no history of clinically significant medical conditions (as described in Exclusion criteria) that would interfere with subject safety, as defined by medical history, physical examination, routine laboratory tests, cardiovascular magnetic resonance imaging or echocardiogram, ECG, pulmonary function tests and Chest X-Ray as determined by the Investigator at a screening evaluation.
- 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
Show all 12Show fewer
- 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.
Who cannot join
- 1) 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:
- 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)
- Any concurrent serious illness including history of malignancy that could interfere with the aims of the study or a subject completing the study. Basal cell carcinoma within 5 years of treatment or with evidence of recurrence is also an exclusion.
Show all 44Show fewer
- Migraine with associated neurological symptoms such as hemiplegia or vision loss. Cluster headache/migraine or prophylactic treatment for migraine
- History or evidence of clinically significant autoimmune disease or known immunodeficiency of any cause (including HIV).
- History of severe psychiatric illness at any time (e.g. inpatient stay, psychosis) or current significant active symptoms of anxiety and/or depression or significant claustrophobia. Consider exclusion in the following cases:
- Volunteers with history of anxiety related symptoms of any severity within the last 2 years if the Generalized Anxiety Disorder-7 score is ≥5 ii) Volunteers with a history of depression of any severity within the last 2 years if the Patient Health Questionnaire-9 score is ≥4 iii) Significant claustrophobia
- Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following injections or venepuncture.
- Other major disease that, in the opinion of the Investigator, could interfere with a subject completing the study and necessary investigations.
- 2) Clinically significant smoking history. Defined as: Current smoker (any smoking including e-cigarettes in the last 3 months) or > 2 pack year smoking history at any time (2 pack years is equivalent to 20 cigarettes daily for 2 years), or use of any nicotine containing products, on more than one occasion, within the last 3 months.
- 3) History or presence of alcohol addiction, or excessive use of alcohol (average weekly intake in excess of 28 units alcohol; one unit being a half glass of beer, a small glass of wine or a measure of spirits)
- 4) Clinically significant history of use of drugs of misuse, with evidence of a negative drugs of misuse urine test required at screening and quarantine admission
- 5) History of anaphylaxis or any allergy likely to be worsened by any component of the study agent or proposed treatment regime.
- 6) Clinically active rhinitis (including hay fever) or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at time of inclusion into the study and/or requiring regular nasal corticosteroids on at least weekly basis, within 30 days of admission to quarantine.
- 7) Any significant abnormality altering the anatomy of the nose or nasopharynx, clinically significant history of epistaxis (nose bleeds) or any nasal or sinus surgery within six months of inoculation
- 8) Clinical, radiological, or laboratory evidence of current active TB disease or latent TB infection
- 9) Previous VZV pneumonia
- 10) Positive HBsAg, HCV or HIV antibodies
- 11) Concurrent use of oral, inhaled or systemic steroid medication or use within the last 6 months (steroids used as a cream or ointment are permissible), or the use of other immunosuppressive agents concurrently or within the last 6 months.
- 12) Concurrent use of medication contraindicated for use with Paxlovid rescue therapy
- 13) Administration of immunoglobulins and/or any blood products within the three months preceding the planned study challenge date
- 14) Current use of any medication or other drug taken through the nasal or inhaled route including cocaine or other recreational drugs
- 15) Plans to receive a live vaccination 30 days prior to enrolment, or any vaccination (i.e. non-live, including a SARS-CoV-2 vaccine) 21 days prior to enrolment and/or plans to take any vaccination 30 days following enrolment
- 16) Current pregnancy or pregnancy within the last 6 months, lactation or intention to become pregnant during study period
- 17) Shares a household with someone with clinically significant immunodeficiency (due to underlying medical condition, medication or pregnancy); or who is extremely clinically vulnerable (previously shielding under Public Health England (now referred to as UK HSA) guidelines)
- 18) Concurrent participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
- 19) Laboratory confirmed (PCR or lateral flow antigen test) SARS-Cov-2 infection, evidence of viral pneumonitis on chest radiograph or a high clinical suspicion of COVID-19 disease in the 3 months preceding enrolment.
- 20) Post COVID-19 symptoms that have not resolved by 1 month prior to enrolment
- 21) Previous hospitalisation with COVID-19 disease or related complications e.g. pulmonary fibrosis on chest x ray
- 22) Family history of 1st degree relative aged 50 years or less with sudden cardiac or unexplained death
- 23) Family history of severe COVID-19 disease or response to any other viral disease e.g. Guillain-Barré
- 24) Family history unavailable or in opinion of investigators not sufficient to assess criteria 22 and 23.
- 25) Clinically significant abnormality on screening chest radiograph
- 26) Clinically significant abnormality of lung function testing
- 27) Clinically significant structural heart disease detected on CMR or echocardiogram, such as abnormal ventricular systolic function, evidence of previous myocardial infarction, previous myocarditis (on CMR) or significant valvular heart disease (more than mild)
- 28) Any clinically significant abnormality of screening blood or urine tests
- 29) Any other significant disease, disorder, or finding, which, in the opinion of the investigator, may either put the volunteer at risk, affect the volunteer's ability to participate in the study or impair interpretation of the study data
- 30) Venous access deemed inadequate for the phlebotomy and cannulation demands of the study.
- For Groups 3 \& 4:
- 31) Previous positive test for SARS CoV-2 infection (PCR or lateral flow antigen test) or a high clinical suspicion of COVID-19 disease at any time.
- 32) Positive Anti-nucleocapsid IgG at screening, unless explainable by vaccination
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Recruiting
Oxford Clinical Research Facility (OxCRF)
Oxford, Oxon, OX3 7LE
Prof. Helen McShane, MD and PhD
- Recruiting
Centre for Clinical Vaccinology and Tropical Medicine
Oxford, Oxon, OX3 7LJ
Prof. Helen McShane, 01865617606, helen.mcshane@ndm.ox.ac.uk
Prof Helen McShane
- Recruiting
Oxford University Hospital NHS Trust
Oxford, Oxon, OX3 9DU
Prof. Helen McShane, MD and PhD
About this study
Official title: A Dose Finding Human Experimental Infection Study With SARS-CoV-2 in Healthy Volunteers With Immunologically Sensitised With Either Previous, SARS-CoV-2 Infection and/or Vaccination Against SARS-CoV2
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.
Read the detailed description
This is a phase I dose escalation challenge study in which increasing titres of wild-type SARS-CoV-2 (1x10^1 TCID_50, 1x10^2TCID_50, 1x10^3TCID_50, 1x10^4TCID_50 and 1x10^5TCID_50) will be administered intranasally to different groups of volunteers in order to achieve a 50% (+/-10%) attack rate as determined by quantitative live viral detection and/or qPCR detection in naso-pharyngeal secretions at two consecutive 12 hourly time points (at least 24 hours after inoculation). Dose escalation will be capped at 10^5 TCID50 and we will proceed to dose confirmation, following DSMB safety review, even if we do not meet our target attack rate of 50% +/- 10%, to enable a larger sample size to assess the dynamic range of protection at that dose and ensure confidence in the negative infection rate at that dose.
A Data Safety Monitoring Board (DSMB) will review safety and quantitative virology at each dose level and will recommend continuation based on emergent data.
Rescue treatment with a single course of oral Paxlovid will commence immediately after any warning symptoms or signs of COVID-19 disease beyond mild disease.
Once the optimal dose of wildtype SARS-CoV-2 has been identified for previously infected volunteers and uninfected vaccinated volunteers (dose escalation groups 1 and 3), further challenge infections in groups 2 and 4 may proceed.
Volunteers will remain in isolation rooms within the clinical trials unit for a minimum of 14 days post inoculation and until demonstration of the absence of live virus in two sequential samples. All 4 groups will together enrol up to 132 volunteers.
This study will be funded by the Wellcome Trust and Department of Health and Social Care (DHSC).
- Conditions
- Coronavirus
- Being tested
- SARS-CoV-2 virus
- Keywords
- Covid-19, SARS-CoV-2, Controlled human infection model, Infection study
- Medical subject headings
- Coronavirus Infections, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SARS-CoV-2 virusBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1A: Low dose challenge | Experimental | Intranasal viral challenge with 1 x 10^1 TCID_50 in previously infected volunteers
N= 6-8 participants Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Biological: SARS-CoV-2 virus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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
Measured: Day 14 or until discharge criteria is met
Secondary outcomes (7)
Determination of SARS-CoV-2 viral dynamics
Assess the SARS-CoV-2 viral dynamics in upper respiratory samples from previously infected (vaccinated or unvaccinated) or uninfected vaccinated individuals including: determination of the incubation period, peak viral load and the mean duration of infectious viral shedding from quantitative virology measured using qPCR and/or live viral detection on naso-oropharyngeal samples.
Measured: Day 365
Exploratory Immunology: Identification of laboratory markers
Ex-vivo ELISpot to SARS-CoV-2 peptide (sfc/1x10^6 PBMC)
Measured: Day 365
Exploratory Immunology: Identification of laboratory markers
Innate, B cell and T cell flow cytometry panel to characterise surface cell markers and antigen specific responses to SARS-CoV-2 peptide before and after SARS-CoV-2 inoculation (% population)
Measured: Day 365
Exploratory Immunology: Identification of laboratory markers
Neutralising peripheral blood antibody analysis to SARS-CoV-2
Measured: Day 365
Exploratory Immunology: Identification of laboratory markers
Single cell RNA-seq on peripheral blood
Measured: Day 365
Exploratory Immunology: Identification of laboratory markers
Cytokine analysis on serum and nasal mucosal lining fluid
Measured: Day 365
Exploratory Immunology: Identification of laboratory markers
ELISA to SARS-CoV-2 peptide from serum and nasal mucosal lining fluid
Measured: Day 365
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2021
- Study start27 May 2021
- Primary completionMar 2024 (estimated)
- Study completionMar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for CoronavirusStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Helen McShane, MD and PhD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04864548
- Sponsor's protocol ID
- COV-CHIM01
- Status last verified
- Jan 2023
- First submitted
- 20 Apr 2021
- Last updated
- 6 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38703782Higham HE, Morgan L, Cooper C, Marshall J, Mawer A, Jackson S, Lopez-Ramon R, Hughes E, Richards D, McShane H, Fullerton JN. Adopting human factors in early phase and experimental medicine research: A nested pilot study observing controlled human infection with SARS-CoV-2. Br J Clin Pharmacol. 2024 Jul;90(7):1586-1599. doi: 10.1111/bcp.15949. Epub 2023 Nov 22.
PubMed 37903635
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Finding Human Experimental Infection Study With SARS-CoV-2 in Healthy Volunteers With Immunologically Sensitised With Either Previous, SARS-CoV-2 Infection and/or Vaccination Against SARS-CoV2
- ClinicalTrials.gov ID
- NCT04864548
- Acronym / sponsor ID
- COV-CHIM01
- Conditions
- Coronavirus
- Keywords
- Covid-19, SARS-CoV-2, Controlled human infection model, Infection study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 132 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 27 May 2021 (actual)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- Mar 2024 (estimated)
- First posted
- 29 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a phase I dose escalation challenge study in which increasing titres of wild-type SARS-CoV-2 (1x10^1 TCID_50, 1x10^2TCID_50, 1x10^3TCID_50, 1x10^4TCID_50 and 1x10^5TCID_50) will be administered intranasally to different groups of volunteers in order to achieve a 50% (+/-10%) attack rate as determined by quantitative live viral detection and/or qPCR detection in naso-pharyngeal secretions at two consecutive 12 hourly time points (at least 24 hours after inoculation). Dose escalation will be capped at 10^5 TCID50 and we will proceed to dose confirmation, following DSMB safety review, even if we do not meet our target attack rate of 50% +/- 10%, to enable a larger sample size to assess the dynamic range of protection at that dose and ensure confidence in the negative infection rate at that dose.
A Data Safety Monitoring Board (DSMB) will review safety and quantitative virology at each dose level and will recommend continuation based on emergent data.
Rescue treatment with a single course of oral Paxlovid will commence immediately after any warning symptoms or signs of COVID-19 disease beyond mild disease.
Once the optimal dose of wildtype SARS-CoV-2 has been identified for previously infected volunteers and uninfected vaccinated volunteers (dose escalation groups 1 and 3), further challenge infections in groups 2 and 4 may proceed.
Volunteers will remain in isolation rooms within the clinical trials unit for a minimum of 14 days post inoculation and until demonstration of the absence of live virus in two sequential samples. All 4 groups will together enrol up to 132 volunteers.
This study will be funded by the Wellcome Trust and Department of Health and Social Care (DHSC).
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Group 1A: Low dose challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^1 TCID_50 in previously infected volunteers N= 6-8 participants |
| Group 1B: Medium dose #1 challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^2 TCID_50 in previously infected volunteers N= 6-8 participants |
| Group 1C: Medium dose #2 challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^3 TCID_50 in previously infected volunteers N= 6-8 participants |
| Group 1D: Medium dose #3 challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^4 TCID_50 in previously infected volunteers N= 4-8 participants |
| Group 1E: High dose challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^5 TCID_50 in previously infected volunteers N= 4-8 participants |
| Group 2: Safety & Dose confirmation Group | Experimental | Biological: SARS-CoV-2 virusIntranasal 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 |
| Group 3a: Medium dose #1 challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^2 TCID_50 in previously uninfected, vaccinated volunteers N=6-8 participants |
| Group 3b: Medium dose #2 challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^3 TCID_50 in previously uninfected, vaccinated volunteers N=4-8 participants |
| Group 3c: Medium dose #3 challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^4 TCID_50 in previously uninfected, vaccinated volunteers N=4-8 participants |
| Group 3d: High dose challenge | Experimental | Biological: SARS-CoV-2 virusIntranasal viral challenge with 1 x 10^5 TCID_50 in previously uninfected, vaccinated volunteers N=4-8 participants |
| Group 4: Safety & Dose confirmation Group | Experimental | Biological: SARS-CoV-2 virusIntranasal 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 |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Aged 18-30 years on proposed date of enrolment.
- Body Mass Index (BMI) ≥18.5 kg/m2and ≤28 kg/m2.
- In good health with no history of clinically significant medical conditions (as described in Exclusion criteria) that would interfere with subject safety, as defined by medical history, physical examination, routine laboratory tests, cardiovascular magnetic resonance imaging or echocardiogram, ECG, pulmonary function tests and Chest X-Ray as determined by the Investigator at a screening evaluation.
- 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
Key exclusion criteria (44 listed)
- 1) 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:
- History of thromboembolic, cardiovascular or cerebrovascular disease
- History or evidence of diabetes mellitus (Type I or Type II)
- Any concurrent serious illness including history of malignancy that could interfere with the aims of the study or a subject completing the study. Basal cell carcinoma within 5 years of treatment or with evidence of recurrence is also an exclusion.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SARS-CoV-2 virusThe 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. | Biological | 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 |
Primary outcome
Occurrence of solicited and unsolicited adverse events
Time frame: Day 84
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
Occurrence of adverse events as determined by medical assessment
Time frame: Day 365
Collection of AE data at each visit time point after SARS-CoV-2 inoculation (Graded 0-3)
Selection of optimal dose(s)
Time frame: Day 14 or until discharge criteria is met
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
7 secondary outcomes
Determination of SARS-CoV-2 viral dynamics
Time frame: Day 365
Exploratory Immunology: Identification of laboratory markers
Time frame: Day 365
Exploratory Immunology: Identification of laboratory markers
Time frame: Day 365
Exploratory Immunology: Identification of laboratory markers
Time frame: Day 365
Exploratory Immunology: Identification of laboratory markers
Time frame: Day 365
Exploratory Immunology: Identification of laboratory markers
Time frame: Day 365
Exploratory Immunology: Identification of laboratory markers
Time frame: Day 365
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2023.
- Derived from this study: PubMed 38703782Jackson 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.
- Derived from this study: PubMed 37903635Higham HE, Morgan L, Cooper C, Marshall J, Mawer A, Jackson S, Lopez-Ramon R, Hughes E, Richards D, McShane H, Fullerton JN. Adopting human factors in early phase and experimental medicine research: A nested pilot study observing controlled human infection with SARS-CoV-2. Br J Clin Pharmacol. 2024 Jul;90(7):1586-1599. doi: 10.1111/bcp.15949. Epub 2023 Nov 22.
- Individual participant dataSharing planned: No
Related trials for Coronavirus
RecruitingPhase 4
A Study to Investigate the Immunogenicity and Safety of mRNA COVID-19 Variant-containing Formulations
SARS-CoV-2
RecruitingObservational study
Natural History of Post-Coronavirus Disease 19 Convalescence at the National Institutes of Health
Post-Coronavirus Disease 19
RecruitingPhase 3
Efficacy and Safety of Tozorakimab in Patients Hospitalised for Viral Lung Infection Requiring Supplemental Oxygen
Viral Lung Infection and Acute Respiratory Failure
RecruitingObservational study
Physiological Finding in Management of COVID 19 Patients
COVID-19 (Coronavirus Disease 2019)
RecruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen McShane, MD and PhD principal investigator
University of Oxford
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SARS-CoV-2 virus in people with Coronavirus, run by University of Oxford at 3 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Volunteer Recruitment Co-ordinator (07990431010, Covid19-challenge@paediatrics.ox.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurrence of solicited and unsolicited adverse events (time frame: Day 84). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04864548, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2023; AzTrials last refreshed its copy on 6 Nov 2026.