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Layout table for study information Study Type : Interventional (Clinical Trial) EstimatedEnrollment : 12390 participants Allocation: Randomized Intervention Model: Sequential Assignment Masking: Single (Participant) Primary Purpose: Prevention Official Title: A Phase 2/3 Study to Determine the Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19 Actual Study Start Date : May 28, 2020 Estimated Primary Completion Date : March 31, 2023 Estimated Study Completion Date : March 31, 2023 Resource links provided by the National Library of Medicine MedlinePlus related topics: COVID-19 (Coronavirus Disease 2019) Vaccines U.S. FDA Resources Arms and Interventions Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Arm Intervention/treatment Experimental: Group 1 a1Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) Biological: ChAdOx1 nCoV-19 (Abs 260)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 Experimental: Group 1 a3Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 1 b1Volunteers 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) boostA 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 Experimental: Group 2 a1Volunteers will receive a single dose ChAdOx1 nCOV19 vaccine, 5x10^10vp (Abs 260) Biological: ChAdOx1 nCoV-19 (Abs 260)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 Experimental: Group 2 a3Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 2 b1.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) boostA 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 Experimental: Group 4 a1Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp (Abs 260) Biological: ChAdOx1 nCoV-19 (Abs 260)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 Experimental: Group 4 b1Volunteers 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) boostA 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 Experimental: Group 4 c1Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 5 a1Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (Abs 260) Biological: ChAdOx1 nCoV-19 (Abs 260)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 Experimental: Group 5 a3Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 5 b1Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x1010vp, (qPCR) Biological: ChAdOx1 nCoV-19 (qPCR)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR Experimental: Group 5 c1Volunteers will receive a single dose ChAdOx1 nCoV19 vaccine, 5x10^10vp, (qPCR) Biological: ChAdOx1 nCoV-19 (Abs 260)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260 Experimental: Group 5 d1Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 5 e1Two 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 0.5mLTwo dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart Experimental: Group 5 f1Two 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 & 0.5mLTwo dose ChAdOx1 nCoV-19 (Covishield 0.9 x 10^11 vp/mL), 0.25mL prime and 0.5mL boost 4-6 weeks apart Experimental: Group 6 a1Volunteers will receive a single dose ofChAdOx1 nCoV19 vaccine, 5x1010vp (qPCR) Biological: ChAdOx1 nCoV-19 (qPCR)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR Experimental: Group 6 b1Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 7 a1Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR) Biological: ChAdOx1 nCoV-19 (qPCR)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR Experimental: Group 7 b1Volunteers will receive two doses of ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)* 4-6 weeks apart Biological: ChAdOx1 nCoV-19 0.5mL prime plus boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 8 a1Volunteers will receive a single dose ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR) Biological: ChAdOx1 nCoV-19 (qPCR)A single dose of 5x10^10vp of ChAdOx1 nCoV-19 measured by qPCR Experimental: Group 8 b1Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 9 a1Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 10 a1Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 11Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Experimental: Group 12Volunteers 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 boostTwo dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 10^10 vp Abs 260) Active Comparator: Single dose MenACWYGroups 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 vaccineStandard single dose of MenACWY vaccineOther Names:Menveo
Nimenrix
Active Comparator: Two dose MenACWY 4 - 6 weeksGroups 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 vaccineTwo standard doses of MenACWY vaccine 4-6 weeks apartOther Names:Menveo
Nimenrix
Active Comparator: Two dose MenACWY minimum 4 weeksGroups 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 apartTwo standard doses of MenACWY vaccine minimum 4 weeks apartOther Names:Menveo
Nimenrix
Outcome Measures Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information Primary Outcome Measures : Assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older. [ Time Frame: Study duration (12 months from last vaccination) ]Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19 Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults [ Time Frame: Study duration (12 months from last vaccination) ]Occurrence of serious adverse events (SAEs) throughout the study duration. Secondary Outcome Measures : 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 [ Time Frame: 7 days post 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-19: occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following [ Time Frame: 7 days post 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-19: occurrence of unsolicited adverse events (AEs) for 28 days following vaccination [ Time Frame: 28 days post 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-19 through standard blood tests (full blood count, liver and kidney function tests) [ Time Frame: 6 months ]Frequency of participants with clinically significant changes from baseline for safety laboratory measures (haematology and biochemistry blood results; except groups 4, 6, 9 & 10) Assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 by measuring the number of disease enhancement episodes [ Time Frame: Study duration (12 months from last vaccination) ]Occurrence of disease enhancement episodes Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: hospital admissions [ Time Frame: Study duration (12 months from last vaccination) ]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 (ICU) admissions associated with COVID-19 Assess efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19: number of 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 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 efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 by measuring incidence of Covid-19 [ Time Frame: Study duration (12 months from last vaccination) ]Proportion of people diagnosed with severe Covid-19 disease (defined according to clinical severity scales) Assess humoral immunogenicity of ChAdOx1 nCoV-19: antibody quantification [ Time Frame: 28 days post vaccination ]Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) Assess humoral immunogenicity of ChAdOx1 nCoV-19: seroconversion [ Time Frame: 28 days post vaccination ]Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination Assess cellular and humoral immunogenicity of ChAdOx1 nCoV-19 through ELISpot assays (groups 1, 2, 7 and 8 only) [ Time Frame: 6 months ]Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein 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 [ Time Frame: 7 days post vaccination ]Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster 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 [ Time Frame: 7 days post vaccination ]Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster 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) [ Time Frame: 28 days post vaccination ]Occurrence of unsolicited adverse events (AEs) for 28 days following booster 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) [ Time Frame: 6 months ]Frequency of participants with clinically significant changes from baseline from pre-booster for safety laboratory measures (haematology and biochemistry blood results) 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 [ Time Frame: 56 days post vaccination ]Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination (seroconversion rates) 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) [ Time Frame: 56 days post vaccination ]Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination Other Outcome Measures: Exploratory Immunology by virus neutralising antibody assays [ Time Frame: 6 months ]Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus Exploratory Immunology by flow cytometry [ Time Frame: 6 months ]Cell analysis by flow cytometry assays Exploratory Immunology by functional antibody assays [ Time Frame: 6 months ]Functional antibody assays Exploratory Immunology: anti-vector immunity [ Time Frame: 6 months ]Anti-vector immunity induced by 1 or 2 doses of ChAdOx1 nCoV-19 Measure exposure to COVID-19 [ Time Frame: 6 months ]Reported by weekly survey to collect information about cases amongst household contacts and friends, contact with the general public, infection control procedures Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection by PCR or NAAT [ Time Frame: 6 months ]Number of PCR or NAAT positive cases of COVID-19 infection Exploratory efficacy against infection: assess efficacy of the candidate ChAdOx1 nCoV-19 against SARS-CoV-2 infection [ Time Frame: 6 months ]Measure of differences in viral loads between those with severe, mild, and asymptomatic PCR+ SARS-CoV-2 infections Compare safety, reactogenicity and immunogenicity between different manufacturing batches of ChAdOx1 nCoV-19 used in COV001 and COV002 [ Time Frame: 6 months ]Differences in safety, reactogenicity and immunogenicity profiles between Group 1 in COV001 and Group 5 in COV002 (proportion of Grade 3 solicited AEs, occurrence of fevers, seroconversion rates at D28, neutralising antibody titres and differences in T-cell responses at D14). Compare safety, reactogenicity and immunogenicity between different methods for measuring doses [ Time Frame: 6 months ]Differences in safety, reactogenicity and immunogenicity profiles between Groups 1, 2, and 5A compared with Groups, 7, 8, and 5B, C and D respectively (proportion of Grade 3 solicited AEs, occurrence of fevers, seroconversion rates at D28, neutralising antibody titres and differences in T-cell responses at D14). Assess vaccine induced mucosal immunity: Nasal mucosa IgA levels at D0 and D28 in a subset of individuals [ Time Frame: 6 months ]Nasal mucosa IgA levels at D0 and D28 in a subset of individuals 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 at 7 days and beyond post SARS-CoV-2 PCR or NAAT positivity Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: differences in antibody titres [ Time Frame: 6 months ]Differences in antibody titres (ELISA and Neutralising antibodies) in participants who received 1 or 2 doses of ChAdOx1 nCoV-19 (groups 1, 2, 7 and 8) Compare immunogenicity of ChAdOx1 nCoV-19 in participants receiving 1 or 2 doses in groups 1, 2, 7 and 8: longevity of immune responses [ Time Frame: 6 months ]Longevity of immune responses in participants who received 1 or 2 doses of ChAdOx1 nCoV-19 Describe the impact of previous vaccination with other ChAdOx1 vectored vaccines on safety and immune responses to ChAdOx1 nCoV-19 [ Time Frame: 6 months ]Differences reactogenicity profile, antibody titres and T-cell responses between groups 5d and 11 and their relationship with anti-vector neutralising antibody titres. Assess the cell-mediated and humoral immunogenicity profile of ChAdOx1 nCoV-19 vaccine in HIV infected adults [ Time Frame: 6 months ]Cell-mediated and humoral responses against SARS-Cov-2 These will be measured by the following: 2ff7e9595c
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