Investigating a Vaccine Against COVID-19

• ClinicalTrials.gov Identifier: NCT04400838
• Recruitment Status: Active, not recruiting
• First Posted: May 26, 2020
• Last Update Posted: January 21, 2022
• Sponsor: University of Oxford
• Information provided by (Responsible Party): University of Oxford

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Coronavirus	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	Phase 2; Phase 3

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 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

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group 1 a1; Volunteers 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 a3; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 1 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) boost; 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
Experimental: Group 2 a1; Volunteers 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 a3; 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; Two 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) boost; 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
Experimental: Group 4 a1; Volunteers 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 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) boost; 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
Experimental: Group 4 c1; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 5 a1; Volunteers 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 a3; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 5 b1; Volunteers 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 c1; Volunteers 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 d1; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 5 e1; 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; Two dose ChAdOx1 nCoV-19 0.5mL (Covishield 0.9 x 10^11 vp/mL), 4-6 weeks apart
Experimental: Group 5 f1; 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; Two 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 a1; Volunteers 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 b1; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 7 a1; Volunteers 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 b1; Volunteers will receive two doses of ChAdOx1nCOV19 vaccine, 5x10^10vp (qPCR)* 4-6 weeks apart	Biological: ChAdOx1 nCoV-19 0.5mL prime plus boost; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 8 a1; Volunteers 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 b1; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 9 a1; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 10 a1; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 11; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Experimental: Group 12; 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; Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10^10 vp Abs 260)
Active Comparator: Single dose MenACWY; 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; Standard single dose of MenACWY vaccine; Other Names: Menveo; Nimenrix
Active Comparator: Two dose MenACWY 4 - 6 weeks; 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; Two standard doses of MenACWY vaccine 4-6 weeks apart; Other Names: Menveo; Nimenrix
Active Comparator: Two dose MenACWY minimum 4 weeks; 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; Two standard doses of MenACWY vaccine minimum 4 weeks apart; Other Names: Menveo; Nimenrix

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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 :

1. 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
2. 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
3. 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
4. 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)
5. 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
6. 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
7. 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
8. 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
9. 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
10. 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)
11. 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)
12. 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
13. 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
14. 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
15. 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
16. 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
17. 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)
18. 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)
19. 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:

1. 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
2. Exploratory Immunology by flow cytometry [ Time Frame: 6 months ]
   Cell analysis by flow cytometry assays
3. Exploratory Immunology by functional antibody assays [ Time Frame: 6 months ]
   Functional antibody assays
4. Exploratory Immunology: anti-vector immunity [ Time Frame: 6 months ]
   Anti-vector immunity induced by 1 or 2 doses of ChAdOx1 nCoV-19
5. 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
6. 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
7. 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
8. 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).
9. 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).
10. 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
11. 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
12. 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)
13. 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
14. 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.
15. 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:

    1. Proportion of seroconversion to antibodies (Ab) against SARS-CoV-2 spike protein measured by ELISA.
    2. Interferon-gamma enzyme linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein
    3. Intracellular Cytokine analyses of CD4 and CD8-specific SARS-CoV-2 spike protein responses
    4. Further exploratory immunology including immune responses to a further dose administered via the NHS national roll out
16. Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults: CD4 count-vaccine immune responses [ Time Frame: 6 months ]
    Relationship between nadir CD4 count vs vaccine immune responses
17. Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults: age vs vaccine immune responses [ Time Frame: 6 months ]
    Relationship between age at enrolment and vaccine immune response
18. Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults [ Time Frame: 6 months ]
    Immune responses to ChAdOx1 nCoV-19 (assessed as described above)
19. Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in HIV infected adults [ Time Frame: Study duration (12 months from last vaccination) ]

    Measured by the following:

    1. Occurrence of serious adverse events (SAEs) throughout the study duration
    2. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination
    3. Occurrence of solicited systemic signs and symptoms for 7 days following each vaccination
    4. Occurrence of unsolicited AEs for 28 days following each vaccination
20. To assess Impact of vaccination on HIV reservoirs [ Time Frame: Study duration (12 months from last vaccination) ]
    Change in Total HIV DNA copies per million CD4 T cells
21. To 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, United Kingdom, SO16 6YD

Castle Hill Hospital

Cottingham, Hull, United Kingdom, HU16 5JQ

St Georges University Hospital NHS Foundation Trust

London, Tooting, United Kingdom, SW17 0QT

University Hospitals Birmingham NHS Foundation Trust

Birmingham, United Kingdom

University Hospitals Bristol and Weston NHS Foundation Trust

Bristol, United Kingdom, BS1 3NU

North Bristol NHS Trust

Bristol, United Kingdom

NIHR Cambridge Clinical Research Facility

Cambridge, United Kingdom, CB2 0QQ

NHS Lothian, Western General Hospital

Edinburgh, United Kingdom, EH4 2XU

Glasgow University and NHS Greater Glasgow & Clyde, New Lister Building, Glasgow Royal Infirmary & Queen Elizabeth University Hospital

Glasgow, United Kingdom, G31 2ER

Liverpool School of Tropical Medicine (LSTM), Accelerator Research Clinic. Clinical Sciences Accelerator

LIverpool, United Kingdom, L7 8XZ

London North West University Healthcare Trust (LNWUH), Northwick Park Hospital

London, United Kingdom, HA1 3UJ

University College London Hospitals NHS Foundation Trust

London, United Kingdom, NW1 2PG

Guy's and St Thomas' NHS Foundation Trust, Department of Infection, St Thomas Hospital

London, United Kingdom, SE1 7EH

Imperial College Healthcare NHS Trust

London, United Kingdom, W12 0HS

The Newcastle upon Tyne Hospitals NHS Foundation Trust, Royal Victoria Infirmary

Newcastle upon Tyne, United Kingdom, NE1 4LP

Public Health Wales

Newport, United Kingdom, NP18 3XQ

University of Nottingham Health Service, Cripps Health Centre, University Park

Nottingham, United Kingdom, NG7 2QW

CCVTM, University of Oxford, Churchill Hospital

Oxford, United Kingdom, OX3 7LE

John Radcliffe Hospital

Oxford, United Kingdom, OX3 9DU

Sheffield Teaching Hospitals, Royal Hallamshire Hospital

Sheffield, United Kingdom, S10 2RX

Sponsors and Collaborators

University of Oxford

Investigators

• Principal Investigator: Andrew Pollard, Prof; University of Oxford

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ogbe A, Pace M, Bittaye M, Tipoe T, Adele S, Alagaratnam J, Aley PK, Ansari MA, Bara A, Broadhead S, Brown A, Brown H, Cappuccini F, Cinardo P, Dejnirattisai W, Ewer KJ, Fok H, Folegatti PM, Fowler J, Godfrey L, Goodman AL, Jackson B, Jenkin D, Jones M, Longet S, Makinson RA, Marchevsky NG, Mathew M, Mazzella A, Mujadidi YF, Parolini L, Petersen C, Plested E, Pollock KM, Rajeswaran T, Ramasamy MN, Rhead S, Robinson H, Robinson N, Sanders H, Serrano S, Tipton T, Waters A, Zacharopoulou P, Barnes E, Dunachie S, Goulder P, Klenerman P, Screaton GR, Winston A, Hill AV, Gilbert SC, Carroll M, Pollard AJ, Fidler S, Fox J, Lambe T, Frater J. Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV. JCI Insight. 2022 Apr 8;7(7):e157031. doi: 10.1172/jci.insight.157031.

Flaxman A, Marchevsky NG, Jenkin D, Aboagye J, Aley PK, Angus B, Belij-Rammerstorfer S, Bibi S, Bittaye M, Cappuccini F, Cicconi P, Clutterbuck EA, Davies S, Dejnirattisai W, Dold C, Ewer KJ, Folegatti PM, Fowler J, Hill AVS, Kerridge S, Minassian AM, Mongkolsapaya J, Mujadidi YF, Plested E, Ramasamy MN, Robinson H, Sanders H, Sheehan E, Smith H, Snape MD, Song R, Woods D, Screaton G, Gilbert SC, Voysey M, Pollard AJ, Lambe T; Oxford COVID Vaccine Trial group. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002). Lancet. 2021 Sep 11;398(10304):981-990. doi: 10.1016/S0140-6736(21)01699-8. Epub 2021 Sep 1.

Frater J, Ewer KJ, Ogbe A, Pace M, Adele S, Adland E, Alagaratnam J, Aley PK, Ali M, Ansari MA, Bara A, Bittaye M, Broadhead S, Brown A, Brown H, Cappuccini F, Cooney E, Dejnirattisai W, Dold C, Fairhead C, Fok H, Folegatti PM, Fowler J, Gibbs C, Goodman AL, Jenkin D, Jones M, Makinson R, Marchevsky NG, Mujadidi YF, Nguyen H, Parolini L, Petersen C, Plested E, Pollock KM, Ramasamy MN, Rhead S, Robinson H, Robinson N, Rongkard P, Ryan F, Serrano S, Tipoe T, Voysey M, Waters A, Zacharopoulou P, Barnes E, Dunachie S, Goulder P, Klenerman P, Screaton GR, Winston A, Hill AVS, Gilbert SC, Pollard AJ, Fidler S, Fox J, Lambe T; Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial. Lancet HIV. 2021 Aug;8(8):e474-e485. doi: 10.1016/S2352-3018(21)00103-X. Epub 2021 Jun 18.

Emary KRW, Golubchik T, Aley PK, Ariani CV, Angus B, Bibi S, Blane B, Bonsall D, Cicconi P, Charlton S, Clutterbuck EA, Collins AM, Cox T, Darton TC, Dold C, Douglas AD, Duncan CJA, Ewer KJ, Flaxman AL, Faust SN, Ferreira DM, Feng S, Finn A, Folegatti PM, Fuskova M, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hallis B, Heath PT, Hay J, Hill HC, Jenkin D, Kerridge S, Lazarus R, Libri V, Lillie PJ, Ludden C, Marchevsky NG, Minassian AM, McGregor AC, Mujadidi YF, Phillips DJ, Plested E, Pollock KM, Robinson H, Smith A, Song R, Snape MD, Sutherland RK, Thomson EC, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Williams CJ, Hill AVS, Lambe T, Gilbert SC, Voysey M, Ramasamy MN, Pollard AJ; COVID-19 Genomics UK consortium; AMPHEUS Project; Oxford COVID-19 Vaccine Trial Group. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial. Lancet. 2021 Apr 10;397(10282):1351-1362. doi: 10.1016/S0140-6736(21)00628-0. Epub 2021 Mar 30.

Voysey M, Costa Clemens SA, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Clutterbuck EA, Collins AM, Cutland CL, Darton TC, Dheda K, Dold C, Duncan CJA, Emary KRW, Ewer KJ, Flaxman A, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Galiza E, Goodman AL, Green CM, Green CA, Greenland M, Hill C, Hill HC, Hirsch I, Izu A, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Libri V, Lillie PJ, Marchevsky NG, Marshall RP, Mendes AVA, Milan EP, Minassian AM, McGregor A, Mujadidi YF, Nana A, Padayachee SD, Phillips DJ, Pittella A, Plested E, Pollock KM, Ramasamy MN, Ritchie AJ, Robinson H, Schwarzbold AV, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Thomson EC, Torok ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, White T, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials. Lancet. 2021 Mar 6;397(10277):881-891. doi: 10.1016/S0140-6736(21)00432-3. Epub 2021 Feb 19. Erratum In: Lancet. 2021 Mar 6;397(10277):880.

Ewer KJ, Barrett JR, Belij-Rammerstorfer S, Sharpe H, Makinson R, Morter R, Flaxman A, Wright D, Bellamy D, Bittaye M, Dold C, Provine NM, Aboagye J, Fowler J, Silk SE, Alderson J, Aley PK, Angus B, Berrie E, Bibi S, Cicconi P, Clutterbuck EA, Chelysheva I, Folegatti PM, Fuskova M, Green CM, Jenkin D, Kerridge S, Lawrie A, Minassian AM, Moore M, Mujadidi Y, Plested E, Poulton I, Ramasamy MN, Robinson H, Song R, Snape MD, Tarrant R, Voysey M, Watson MEE, Douglas AD, Hill AVS, Gilbert SC, Pollard AJ, Lambe T; Oxford COVID Vaccine Trial Group. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial. Nat Med. 2021 Feb;27(2):270-278. doi: 10.1038/s41591-020-01194-5. Epub 2020 Dec 17. Erratum In: Nat Med. 2021 Jun;27(6):1116.

Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, Angus B, Baillie VL, Barnabas SL, Bhorat QE, Bibi S, Briner C, Cicconi P, Collins AM, Colin-Jones R, Cutland CL, Darton TC, Dheda K, Duncan CJA, Emary KRW, Ewer KJ, Fairlie L, Faust SN, Feng S, Ferreira DM, Finn A, Goodman AL, Green CM, Green CA, Heath PT, Hill C, Hill H, Hirsch I, Hodgson SHC, Izu A, Jackson S, Jenkin D, Joe CCD, Kerridge S, Koen A, Kwatra G, Lazarus R, Lawrie AM, Lelliott A, Libri V, Lillie PJ, Mallory R, Mendes AVA, Milan EP, Minassian AM, McGregor A, Morrison H, Mujadidi YF, Nana A, O'Reilly PJ, Padayachee SD, Pittella A, Plested E, Pollock KM, Ramasamy MN, Rhead S, Schwarzbold AV, Singh N, Smith A, Song R, Snape MD, Sprinz E, Sutherland RK, Tarrant R, Thomson EC, Torok ME, Toshner M, Turner DPJ, Vekemans J, Villafana TL, Watson MEE, Williams CJ, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2021 Jan 9;397(10269):99-111. doi: 10.1016/S0140-6736(20)32661-1. Epub 2020 Dec 8. Erratum In: Lancet. 2021 Jan 9;397(10269):98.

Ramasamy MN, Minassian AM, Ewer KJ, Flaxman AL, Folegatti PM, Owens DR, Voysey M, Aley PK, Angus B, Babbage G, Belij-Rammerstorfer S, Berry L, Bibi S, Bittaye M, Cathie K, Chappell H, Charlton S, Cicconi P, Clutterbuck EA, Colin-Jones R, Dold C, Emary KRW, Fedosyuk S, Fuskova M, Gbesemete D, Green C, Hallis B, Hou MM, Jenkin D, Joe CCD, Kelly EJ, Kerridge S, Lawrie AM, Lelliott A, Lwin MN, Makinson R, Marchevsky NG, Mujadidi Y, Munro APS, Pacurar M, Plested E, Rand J, Rawlinson T, Rhead S, Robinson H, Ritchie AJ, Ross-Russell AL, Saich S, Singh N, Smith CC, Snape MD, Song R, Tarrant R, Themistocleous Y, Thomas KM, Villafana TL, Warren SC, Watson MEE, Douglas AD, Hill AVS, Lambe T, Gilbert SC, Faust SN, Pollard AJ; Oxford COVID Vaccine Trial Group. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial. Lancet. 2021 Dec 19;396(10267):1979-1993. doi: 10.1016/S0140-6736(20)32466-1. Epub 2020 Nov 19. Erratum In: Lancet. 2021 Dec 19;396(10267):1978. Lancet. 2021 Apr 10;397(10282):1350.

• Responsible Party: University of Oxford
• ClinicalTrials.gov Identifier: NCT04400838
• Other Study ID Numbers: COV002
• First Posted: May 26, 2020
• Last Update Posted: January 21, 2022
• Last Verified: January 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Oxford:

Covid-19; ChAdOx1 nCov19; sars-cov-2; vaccine

Additional relevant MeSH terms:

COVID-19; Coronavirus Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs