Investigating a Vaccine Against COVID-19

Study Overview
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Brief Summary
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A phase 2/3 study to determine the efficacy, safety and immunogenicity of the candidate Coronavirus Disease (COVID-19) vaccine ChAdOx1 nCoV-19 in healthy UK volunteers.

Detailed Description
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There will be 12 study groups and it is anticipated that a total of 12,390 volunteers will be enrolled. Groups 1, 7 & 9 are adults aged 56-69 years; groups 2, 8 & 10 are adults 70 years and over; groups 4, 5 & 6 are adults aged 18-55 years; group 11 is adults aged 18-55 years who have previously received a ChAdOx vectored vaccine; group 12 is HIV positive adults aged 18-55 years. The vaccine will be administered intramuscularly into the deltoid of the non-dominant arm (preferably). All subjects will undergo follow-up for a total of 1 year post last vaccination. Additional visits or procedures may be performed at the discretion of the investigators, e.g., further medical history and physical examination, or additional blood tests and other investigations if clinically relevant

Official Title
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A Phase 2/3 Study to Determine the Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19

Conditions
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Coronavirus

Intervention / Treatment
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* Biological: ChAdOx1 nCoV-19 (Abs 260)
* Biological: MenACWY vaccine
* Biological: ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost
* Biological: Two dose MenACWY vaccine
* Biological: ChAdOx1 nCoV-19 (qPCR)
* Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost
* Biological: Two dose MenACWY vaccine min. 4 weeks apart
* Biological: Two dose ChAdOx1 nCoV-19/Covishield 0.5mL
* Biological: Two dose ChAdOx1 nCoV-19/Covishield 0.25mL & 0.5mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults aged 18 - 55 years (groups 4, 5, 6 and 11) Adults aged 56-69 years (groups 1, 7, and 9) Adults aged 70 years and older (groups 2, 8, and 10) Able and willing (in the Investigator's opinion) to comply with all study requirements. 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 of childbearing potential 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. Additional Inclusion criteria to Group 12 (HIV sub-study): HIV positive Receiving antiretroviral therapy Undetectable HIV viral load CD4>350 cells/mL Exclusion Criteria: • Participation in COVID-19 prophylactic drug trials for the duration of the study. Note: Participation in COVID-19 treatment trials is allowed in the event of hospitalisation due to COVID-19. The COV002 study team should be informed as soon as possible. • Participation in SARS-CoV-2 serological surveys where participants are informed of their serostatus for the duration of the study. Note: Disclosure of serostatus post enrolment may accidently unblind participants to group allocation. Participation in COV002 can only be allowed if volunteers are kept blinded to their serology results from local/national serological surveys Receipt of any vaccine (licensed or investigational) 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 vaccination. Participants will be encouraged to receive these vaccinations at least 7 days before or after their study vaccine. Prior or planned receipt of an investigational or licensed vaccine or product likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines). This exclusion criteria will not apply to group 11, as recruitment will be targeted at those volunteers who previously received a ChAdOx1 vectored vaccine. 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 (except group 12, where HIV infected participants are allowed); 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) History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY Any history of angioedema. Any history of anaphylaxis. Pregnancy, lactation or willingness/intention to become pregnant during the study. Current diagnosis of or treatment for 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. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) Suspected or known current alcohol or drug dependency. 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. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild/moderate well controlled comorbidities are allowed) History of laboratory confirmed COVID-19 (except groups 5d, 5e, 5f, 9, 10 and 11). Seropositivity to SARS-CoV-2 before enrolment (except groups 5d, 5e, 5f, 9, 10 and 11) NB: volunteers with previous NAAT positive results are also allowed in groups 9, 10 and 11 Additional Exclusion criteria to Groups 4, 6, 9 and 10 History of allergic disease or reactions likely to be exacerbated by Paracetamol Note: Caution should be taken when recommending paracetamol to adults who already take paracetamol chronically Re-vaccination exclusion criteria (two-dose groups only) 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. (Protocol 19.0) 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

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: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 a1<br>Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) | Biological: ChAdOx1 nCoV-19 (Abs 260)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260<br>|
| Experimental: Group 1 a3<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks from prime | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 1 b1<br>Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost (4-6 weeks apart) | Biological: ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 and 2.2x10^10vp ChAdOx1 nCoV-19 boost measured by qPCR 4-6 weeks later<br>|
| Experimental: Group 2 a1<br>Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) | Biological: ChAdOx1 nCoV-19 (Abs 260)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260<br>|
| Experimental: Group 2 a3<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 2 b1<br>.Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 and 2.2x10^10vp ChAdOx1 nCoV-19 boost measured by qPCR 4-6 weeks later<br>|
| Experimental: Group 4 a1<br>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp (Abs 260) | Biological: ChAdOx1 nCoV-19 (Abs 260)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260<br>|
| Experimental: Group 4 b1<br>Volunteers will receive two dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) prime and 2.2x10^10vp (qPCR) boost 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 (Abs 260) + 2.2x10^10vp (qPCR) boost<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 and 2.2x10^10vp ChAdOx1 nCoV-19 boost measured by qPCR 4-6 weeks later<br>|
| Experimental: Group 4 c1<br>Volunteers will receive two doses of ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs260) prime and 2.2x10^10vp (qPCR) boost*, at least 4 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 5 a1<br>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (Abs 260) | Biological: ChAdOx1 nCoV-19 (Abs 260)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260<br>|
| Experimental: Group 5 a3<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine: 5x10^10vp (Abs 260) prime and 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260) boost, minimum 4 weeks from prime | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 5 b1<br>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x1010vp, (qPCR) | Biological: ChAdOx1 nCoV-19 (qPCR)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR<br>|
| Experimental: Group 5 c1<br>Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (qPCR) | Biological: ChAdOx1 nCoV-19 (Abs 260)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260<br>|
| Experimental: Group 5 d1<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 5 e1<br>Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart | Biological: Two dose ChAdOx1 nCoV-19/Covishield 0.5mL<br>* Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart<br>|
| Experimental: Group 5 f1<br>Two dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart | Biological: Two dose ChAdOx1 nCoV-19/Covishield 0.25mL & 0.5mL<br>* Two dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart<br>|
| Experimental: Group 6 a1<br>Volunteers will receive a single dose ofChAdOx1 nCoV19 vaccine, 5x1010vp (qPCR) | Biological: ChAdOx1 nCoV-19 (qPCR)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR<br>|
| Experimental: Group 6 b1<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 5x1010vp (Abs260) prime and 0.5mL (3.5 - 6.5 × 1010 vp, Abs 260)* boost* at least 4 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 7 a1<br>Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR) | Biological: ChAdOx1 nCoV-19 (qPCR)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR<br>|
| Experimental: Group 7 b1<br>Volunteers will receive two doses of ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)* 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 8 a1<br>Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR) | Biological: ChAdOx1 nCoV-19 (qPCR)<br>* A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR<br>|
| Experimental: Group 8 b1<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 9 a1<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 10 a1<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 11<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Experimental: Group 12<br>Volunteers will receive two doses of ChAdOx1 nCoV19 vaccine, 0.5mL (3.5 - 6.5 × 10^10 vp, Abs 260)* 4-6 weeks apart | Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost<br>* Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)<br>|
| Active Comparator: Single dose MenACWY<br>Groups 1 a2, 2 a2, 4 a2, 5 a2, 5 b2, 5 c2, 6 a2, 7 a2 & 8 a2 will receive a standard single dose of MenACWY vaccine | Biological: MenACWY vaccine<br>* Standard single dose of MenACWY vaccine<br>* Other names: Nimenrix;|
| Active Comparator: Two dose MenACWY 4 - 6 weeks<br>Groups 1 b2, 2 b2, 4 b2, 5 d2, 7 b2, 8 b2, 9 a2 & 10 a2 will receive two doses of MenACWY 4-6 weeks apart | Biological: Two dose MenACWY vaccine<br>* Two standard doses of MenACWY vaccine 4-6 weeks apart<br>* Other names: Nimenrix;|
| Active Comparator: Two dose MenACWY minimum 4 weeks<br>Groups 1 a4, 2 a4, 4 c2, 5 a4, 6b2 will receive two doses of MenACWY at least 4 weeks apart | Biological: Two dose MenACWY vaccine min. 4 weeks apart<br>* Two standard doses of MenACWY vaccine minimum 4 weeks apart<br>* Other names: Nimenrix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older. | Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19 | Study duration (12 months from last vaccination) | 
| Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults | Occurrence of serious adverse events (SAEs) throughout the study duration. | Study duration (12 months from last vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of solicited local reactogenicity signs and symptoms for 7 days following | Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination | 7 days post vaccination | 
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following | Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination | 7 days post vaccination | 
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: occurrence of unsolicited adverse events (AEs) for 28 days following vaccination | Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination | 28 days post vaccination | 
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 through standard blood tests (full blood count, liver and kidney function tests) | Frequency of participants with clinically significant changes from baseline for safety laboratory measures (haematology and biochemistry blood results; except groups 4, 6, 9 & 10) | 6 months | 
| Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 by measuring the number of disease enhancement episodes | Occurrence of disease enhancement episodes | Study duration (12 months from last vaccination) | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: hospital admissions | Number of hospital admissions associated with COVID-19 | Study duration (12 months from last vaccination) | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 | Number of intensive care unit (ICU) admissions associated with COVID-19 | 6 months | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: number of 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 by measuring seroconversion rates | Proportion of people who become seropositive for non-Spike SARS-CoV-2 antigens during the study | 6 months | 
| Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring incidence of Covid-19 | Proportion of people diagnosed with severe Covid-19 disease (defined according to clinical severity scales) | Study duration (12 months from last vaccination) | 
| Assess humoral immunogenicity of ChAdOx1 nCoV-19: antibody quantification | Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) | 28 days post vaccination | 
| Assess humoral immunogenicity of ChAdOx1 nCoV-19: seroconversion | Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination | 28 days post vaccination | 
| Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays (groups 1, 2, 7 and 8 only) | Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein | 6 months | 
| Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1, 2, 7 and 8 only): local reactogenicity | Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination | 7 days post vaccination | 
| Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only): systemic reactogenicity | Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination | 7 days post vaccination | 
| Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) | Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination | 28 days post vaccination | 
| Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) through standard blood tests (full blood count, liver and kidney function tests) | Frequency of participants with clinically significant changes from baseline from pre-booster for safety laboratory measures (haematology and biochemistry blood results) | 6 months | 
| Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) via seroconversion | Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination (seroconversion rates) | 56 days post vaccination | 
| Assess the safety and immunogenicity of a booster dose of ChAdOx1 nCoV-19 in older adults aged 56 years or older (two-dose schedules for groups 1 and 2 only) | Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination | 56 days post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Covid-19, ChAdOx1 nCov19, sars-cov-2, vaccine