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A Study of a Candidate COVID-19 Vaccine (COV001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04324606
Recruitment Status : Active, not recruiting
First Posted : March 27, 2020
Last Update Posted : April 13, 2021
Sponsor:
Information provided by (Responsible Party):
University of Oxford

Tracking Information
First Submitted Date  ICMJE March 20, 2020
First Posted Date  ICMJE March 27, 2020
Last Update Posted Date April 13, 2021
Actual Study Start Date  ICMJE April 23, 2020
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases [ Time Frame: 6 months ]
    Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19
  • Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs) [ Time Frame: Throughout the study, average of 18 months ]
    Occurrence of serious adverse events (SAEs) throughout the study until a cutoff date of 1st July 2021 or 6 months post late vaccination visit, whichever is latest
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases [ Time Frame: 6 months ]
    Number of virologically confirmed (PCR positive) symptomatic cases of COVID-19
  • Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs) [ Time Frame: 6 months ]
    Occurrence of serious adverse events (SAEs) throughout the study duration
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2021)
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
    Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited systemic reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
    Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs) [ Time Frame: 7 or 28 days following vaccination ]
    Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination (7 days following vaccination for groups 1c, 1d, 5a & 5b)
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests [ Time Frame: 6 months ]
    Change from baseline for safety laboratory measures (haematology and biochemistry blood results)
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes [ Time Frame: 6 months ]
    Occurrence of disease enhancement episodes
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by hospital admissions [ Time Frame: 6 months ]
    Number of hospital admissions associated with COVID-19
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by ICU admissions [ Time Frame: 6 months ]
    Number of intensive care unit admissions associated with COVID-19
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by COVID-19 related deaths [ Time Frame: 6 months ]
    Number of deaths associated with COVID-19
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
    Occurrence of severe COVID-19 disease (defined according to clinical severity scales)
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates [ Time Frame: 6 months ]
    Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study
  • Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays [ Time Frame: 6 months ]
    Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
  • Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 [ Time Frame: 6 months ]
    Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2020)
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
    Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited systemic reactogenicity signs and symptoms [ Time Frame: 7 days following vaccination ]
    Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs) [ Time Frame: 28 days following vaccination ]
    Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests [ Time Frame: 6 months ]
    Change from baseline for safety laboratory measures (haematology and biochemistry blood results)
  • Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes [ Time Frame: 6 months ]
    Occurrence of disease enhancement episodes
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
    Number of deaths associated with COVID-19
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
    Number of hospital admissions associated with COVID-19
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 [ Time Frame: 6 months ]
    Number of intensive care unit admissions associated with COVID-19
  • Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates [ Time Frame: 6 months ]
    Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study
  • Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays [ Time Frame: 6 months ]
    Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
  • Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 [ Time Frame: 6 months ]
    Enzyme-linked immunosorbent assay (ELISA) to quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates)
Current Other Pre-specified Outcome Measures
 (submitted: April 8, 2021)
  • Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through Virus neutralising antibody assays [ Time Frame: 6 months ]
    Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus
  • Assess safety, reactogenicity, immunogenicity and efficacy endpoints, for participants receiving prophylactic paracetamol [ Time Frame: 6 months ]
    All safety, reactogenicity, immunogenicity and efficacy endpoints
  • Assess immunogenicity of ChAdOx1 nCoV-19 given as homologous prime-boost [ Time Frame: 6 months ]
    Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) post boost
  • Compare viral shedding on stool samples of SARS-CoV-2 PCR or NAAT positive individuals [ Time Frame: 6 months ]
    Differences in viral shedding on stool between vaccine and comparator arms at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity
  • Assess immunogenicity of a delayed three dose ChAdOx1 nCoV-19 schedule [ Time Frame: Blood samples drawn at LV14, LV28 and LV182 ]
    Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) post boost
  • assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients [ Time Frame: Throughout the study, average of 18 months ]
    Immunological endpoints (antibody & cellular responses to SARS-COV2 spike protein) and COVID-19 disease endpoints (SARS-COV2 PCR positivity plus symptoms) in ChAdOx1 nCoV-19 recipients
Original Other Pre-specified Outcome Measures
 (submitted: March 26, 2020)
Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through Virus neutralising antibody assays [ Time Frame: 6 months ]
Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus
 
Descriptive Information
Brief Title  ICMJE A Study of a Candidate COVID-19 Vaccine (COV001)
Official Title  ICMJE A Phase I/II Study to Determine Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19 in UK Healthy Adult Volunteers
Brief Summary A phase I/II single-blinded, randomised, multi-centre study to determine efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in UK healthy adult volunteers aged 18-55 years. The vaccine will be administered intramuscularly (IM) into the deltoid region of the arm
Detailed Description There will be 4 study groups and it is anticipated that a total of 1090 volunteers will be enrolled. Volunteers will participate in the study for approximately 12 months from last vaccination visit (approximately 15 months from enrolment for participants receiving 2 doses)
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE Coronavirus
Intervention  ICMJE
  • Biological: ChAdOx1 nCoV-19
    A single dose of 5x10^10vp of ChAdOx1 nCoV-19
  • Biological: MenACWY
    Standard single dose of MenACWY vaccine delivered intramuscularly
  • Biological: ChAdOx1 nCoV-19 full boost
    A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10^10vp of ChAdOx1 nCoV-19
  • Biological: ChAdOx1 nCoV-19 half boost
    A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 2.5x10^10vp of ChAdOx1 nCoV-19
  • Biological: MenACWY boost
    A standard dose of MenACWY followed by a boost dose of MenACWY
  • Drug: Paracetamol
    1g every 6 hours for 24 hours
  • Biological: ChAdOx1 nCoV-19 0.5mL boost
    A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp)
  • Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)
    A dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) 9 months after receiving a single or double dose of 5x10^10vp of ChAdOx1 nCoV-19
  • Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)
    A dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) 9 months after receiving a single or double dose of MenACWY, then a boost 4-12 weeks later
Study Arms  ICMJE
  • Experimental: Group 1a
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19
    Intervention: Biological: ChAdOx1 nCoV-19
  • Active Comparator: Group 1b
    Volunteers will receive a standard single dose of MenACWY vaccine
    Intervention: Biological: MenACWY
  • Experimental: Group 1c
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and a boost dose of 5x10^10vp ChAdOx1 nCoV-19 9 months later
    Interventions:
    • Biological: ChAdOx1 nCoV-19
    • Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)
  • Experimental: Group 1d
    Volunteers will receive a standard single dose of MenACWY vaccine. 9 moths later they will receive two doses of 5x10^10vp ChAdOx1 nCoV-19 4-12 weeks apart
    Interventions:
    • Biological: MenACWY
    • Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)
  • Experimental: Group 2a
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19
    Intervention: Biological: ChAdOx1 nCoV-19
  • Active Comparator: Group 2b
    Volunteers will receive a standard single dose of MenACWY vaccine
    Intervention: Biological: MenACWY
  • Experimental: Group 2c
    Volunteers will receive two doses of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and week 8
    Intervention: Biological: ChAdOx1 nCoV-19 full boost
  • Experimental: Group 2d
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and a boost dose of 2.5x10^10vp ChAdOx1 nCoV-19 at week 8
    Intervention: Biological: ChAdOx1 nCoV-19 half boost
  • Active Comparator: Group 2e
    Volunteers will receive two standard single doses of MenACWY vaccine at week 0 and week 8
    Intervention: Biological: MenACWY boost
  • Experimental: Group 2f
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) a minimum of 4 weeks later
    Intervention: Biological: ChAdOx1 nCoV-19 0.5mL boost
  • Active Comparator: Group 2g
    Volunteers will receive two standard single doses of MenACWY vaccine a minimum of 4 weeks apart
    Intervention: Biological: MenACWY boost
  • Experimental: Group 3a
    Volunteers will receive one dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and one dose of 5x10^10vp ChAdOx1 nCoV-19 at week 4
    Intervention: Biological: ChAdOx1 nCoV-19 full boost
  • Experimental: Group 3b
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0, a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) a minimum of 4 weeks later, and a third dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) at 9 months
    Interventions:
    • Biological: ChAdOx1 nCoV-19 full boost
    • Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)
  • Experimental: Group 4a
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19
    Interventions:
    • Biological: ChAdOx1 nCoV-19
    • Drug: Paracetamol
  • Active Comparator: Group 4b
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 delivered intramuscularly
    Interventions:
    • Biological: MenACWY
    • Drug: Paracetamol
  • Experimental: Group 4c
    Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and a boost dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) a minimum of 4 weeks later
    Interventions:
    • Biological: ChAdOx1 nCoV-19
    • Biological: ChAdOx1 nCoV-19 0.5mL boost
  • Active Comparator: Group 4d
    Volunteers will receive two standard single doses of MenACWY vaccine a minimum of 4 weeks apart
    Intervention: Biological: MenACWY boost
  • Experimental: Group 5a
    Volunteers will receive two doses of 5x10^10vp ChAdOx1 nCoV-19 ≤ 16 weeks apart, and a third dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) at 9 months
    Interventions:
    • Biological: ChAdOx1 nCoV-19 full boost
    • Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)
  • Experimental: Group 5b
    Volunteers will receive two standard single doses of MenACWY vaccine ≤ 16 weeks apart, a dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) at 9 months then a second dose of ChAdOx1 nCoV-19 0.5mL (3.5-6.5x1010vp) 4-12 weeks later
    Interventions:
    • Biological: MenACWY boost
    • Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 7, 2020)
1090
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2020)
510
Estimated Study Completion Date  ICMJE October 2021
Estimated Primary Completion Date October 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

The volunteer must satisfy all the following criteria to be eligible for the study:

  • Healthy adults aged 18-55 years.
  • Able and willing (in the Investigator's opinion) to comply with all study requirements (participants must not rely on public transport or taxis).
  • Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner and access all medical records when relevant to study procedures.
  • For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and vaccination.
  • Agreement to refrain from blood donation during the course of the study.
  • Provide written informed consent.

Exclusion Criteria

The volunteer may not enter the study if any of the following apply:

  • Planned receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination .with the exception of the licensed seasonal influenza vaccination and the licensed pneumococcal vaccine. Participants will be encouraged to receive this vaccination at least 7 days before or after their study vaccine.
  • Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines).
  • Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
  • Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent severe infections and use of immunosuppressant medication within the past 6 months, except topical steroids or short-term oral steroids (course lasting <14 days) .
  • Any autoimmune conditions, except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease not requiring immunosuppressive or immunomodulatory therapy.
  • History of allergic disease or reactions likely to be exacerbated by any component of the ChAdOx1 nCoV-19 or MenACWY vaccines.
  • Any history of angioedema .
  • Any history of anaphylaxis .
  • Pregnancy, lactation or willingness/intention to become pregnant during the study.
  • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
  • History of serious psychiatric condition likely to affect participation in the study (e.g. ongoing severe depression, history of admission to an in-patient psychiatric facility, recent suicidal ideation, history of suicide attempt, bipolar disorder, personality disorder, alcohol and drug dependency, severe eating disorder, psychosis, use of mood stabilisers or antipsychotic medication).
  • Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture.
  • Any other serious chronic illness requiring hospital specialist supervision.
  • Chronic respiratory diseases, including mild asthma (resolved childhood asthma is allowed)
  • Chronic cardiovascular disease (including hypertension), gastrointestinal disease, liver disease (except Gilberts Syndrome), renal disease, endocrine disorder (including diabetes) and neurological illness (excluding migraine)
  • Seriously overweight (BMI≥40 Kg/m2) or underweight (BMI≤18 Kg/m2)
  • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week.
  • Suspected or known injecting drug abuse in the 5 years preceding enrolment.
  • Any clinically significant abnormal finding on screening biochemistry, haematology blood tests or urinalysis.
  • Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
  • History of laboratory confirmed COVID-19.
  • New onset of fever or a cough or shortness of breath or anosmia/ageusia since February 2020. Should a reliable test become available, this exclusion criteria will be replaced with seropositivity for SARS-CoV-2 before enrolment.
  • Those who have been at high risk of exposure before enrolment, including but not limited to: close contacts of confirmed COVID-19 cases, anyone who had to self-isolate as a result of a symptomatic household member, frontline healthcare professionals working in A&E, ICU and other higher risk areas. Should a reliable test become available, this exclusion criteria will be replaced with seropositivity for SARS-CoV-2 before enrolment.
  • Living in the same household as any vulnerable groups at risk of severe COVID-19 disease (as per Public Health England guidance)

Additional exclusion criteria (subset of participants receiving Paracetamol in group 4 only)

• History of allergic disease or reactions likely to be exacerbated by Paracetamol

Re-vaccination exclusion criteria:

The following AEs associated with any vaccine, or identified on or before the day of vaccination constitute absolute contraindications to further administration of an IMP to the volunteer in question. If any of these events occur during the study, the subject will not be eligible to receive a booster dose and will be followed up by the clinical team or their GP until resolution or stabilisation of the event:

  • Anaphylactic reaction following administration of vaccine
  • Pregnancy. An exception to this will be prior to receipt of a booster dose at extra visit B. If a pregnant woman has discussed vaccination with their usual clinician (e.g. GP) and chooses to receive a COVID-19 vaccination, this may be administered by the trial team as part of extra visit B or as part of the provision of treatment to controls
  • Any AE that in the opinion of the Investigator may affect the safety of the participant or the interpretation of the study results
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04324606
Other Study ID Numbers  ICMJE COV001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Oxford
Study Sponsor  ICMJE University of Oxford
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Andrew Pollard, Prof University of Oxford
PRS Account University of Oxford
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP