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

Study Overview
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Brief Summary
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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
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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)

Official Title
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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

Conditions
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Coronavirus

Intervention / Treatment
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* Biological: ChAdOx1 nCoV-19
* Biological: MenACWY
* Biological: ChAdOx1 nCoV-19 full boost
* Biological: ChAdOx1 nCoV-19 half boost
* Biological: MenACWY boost
* Drug: Paracetamol
* Biological: ChAdOx1 nCoV-19 0.5mL boost
* Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)
* Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1a<br>Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 | Biological: ChAdOx1 nCoV-19<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19<br>|
| Active Comparator: Group 1b<br>Volunteers will receive a standard single dose of MenACWY vaccine | Biological: MenACWY<br>* Standard single dose of MenACWY vaccine delivered intramuscularly<br>|
| Experimental: Group 1c<br>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 | Biological: ChAdOx1 nCoV-19<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19<br>Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)<br>* 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<br>|
| Experimental: Group 1d<br>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 | Biological: MenACWY<br>* Standard single dose of MenACWY vaccine delivered intramuscularly<br>Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)<br>* 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<br>|
| Experimental: Group 2a<br>Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 | Biological: ChAdOx1 nCoV-19<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19<br>|
| Active Comparator: Group 2b<br>Volunteers will receive a standard single dose of MenACWY vaccine | Biological: MenACWY<br>* Standard single dose of MenACWY vaccine delivered intramuscularly<br>|
| Experimental: Group 2c<br>Volunteers will receive two doses of 5x10^10vp ChAdOx1 nCoV-19 at week 0 and week 8 | Biological: ChAdOx1 nCoV-19 full boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10^10vp of ChAdOx1 nCoV-19<br>|
| Experimental: Group 2d<br>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 | Biological: ChAdOx1 nCoV-19 half boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 2.5x10^10vp of ChAdOx1 nCoV-19<br>|
| Active Comparator: Group 2e<br>Volunteers will receive two standard single doses of MenACWY vaccine at week 0 and week 8 | Biological: MenACWY boost<br>* A standard dose of MenACWY followed by a boost dose of MenACWY<br>|
| Experimental: Group 2f<br>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 | Biological: ChAdOx1 nCoV-19 0.5mL boost<br>* 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)<br>|
| Active Comparator: Group 2g<br>Volunteers will receive two standard single doses of MenACWY vaccine a minimum of 4 weeks apart | Biological: MenACWY boost<br>* A standard dose of MenACWY followed by a boost dose of MenACWY<br>|
| Experimental: Group 3a<br>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 | Biological: ChAdOx1 nCoV-19 full boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10^10vp of ChAdOx1 nCoV-19<br>|
| Experimental: Group 3b<br>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 | Biological: ChAdOx1 nCoV-19 full boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10^10vp of ChAdOx1 nCoV-19<br>Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)<br>* 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<br>|
| Experimental: Group 4a<br>Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 | Biological: ChAdOx1 nCoV-19<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19<br>Drug: Paracetamol<br>* 1g every 6 hours for 24 hours<br>|
| Active Comparator: Group 4b<br>Volunteers will receive a single dose of 5x10^10vp ChAdOx1 nCoV-19 delivered intramuscularly | Biological: MenACWY<br>* Standard single dose of MenACWY vaccine delivered intramuscularly<br>Drug: Paracetamol<br>* 1g every 6 hours for 24 hours<br>|
| Experimental: Group 4c<br>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 | Biological: ChAdOx1 nCoV-19<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19<br>Biological: ChAdOx1 nCoV-19 0.5mL boost<br>* 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)<br>|
| Active Comparator: Group 4d<br>Volunteers will receive two standard single doses of MenACWY vaccine a minimum of 4 weeks apart | Biological: MenACWY boost<br>* A standard dose of MenACWY followed by a boost dose of MenACWY<br>|
| Experimental: Group 5a<br>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 | Biological: ChAdOx1 nCoV-19 full boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 followed by a boost dose of 5x10^10vp of ChAdOx1 nCoV-19<br>Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine (LV)<br>* 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<br>|
| Experimental: Group 5b<br>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 | Biological: MenACWY boost<br>* A standard dose of MenACWY followed by a boost dose of MenACWY<br>Biological: ChAdOx1 nCoV-19 0.5mL (3.5-6.5x10^10vp) late vaccine two (LVT)<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19: Number of virologically confirmed (PCR positive) symptomatic cases | Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19 | 6 months | 
| Assess the safety of the candidate vaccine ChAdOx1 nCoV: Occurrence of serious adverse events (SAEs) | 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 | Throughout the study, average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of solicited local reactogenicity signs and symptoms | Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination | 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 | Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination | 7 days following vaccination | 
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV: Occurrence of unsolicited adverse events (AEs) | Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination (7 days following vaccination for groups 1c, 1d, 5a & 5b) | 7 or 28 days following vaccination | 
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV through standard blood tests | Change from baseline for safety laboratory measures (haematology and biochemistry blood results) | 6 months | 
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV by measuring the number of disease enhancement episodes | Occurrence of disease enhancement episodes | 6 months | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by hospital admissions | Number of hospital admissions associated with COVID-19 | 6 months | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by ICU admissions | Number of intensive care unit admissions associated with COVID-19 | 6 months | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by COVID-19 related deaths | Number of deaths associated with COVID-19 | 6 months | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 | Occurrence of severe COVID-19 disease (defined according to clinical severity scales) | 6 months | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring seroconversion rates | Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study | 6 months | 
| Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays | Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein | 6 months | 
| Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 | Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Vaccine