Coronavirus
Conditions
Keywords
Covid-19, ChAdOx1 nCov19, sars-cov-2, vaccine
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.
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
Interventions
BIOLOGICALChAdOx1 nCoV-19 (Abs 260)
A single dose of 5x10\^10vp of ChAdOx1 nCoV-19 measured by spectrophotometry at Abs260
BIOLOGICALMenACWY vaccine
Standard single dose of MenACWY vaccine
BIOLOGICALChAdOx1 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
BIOLOGICALTwo dose MenACWY vaccine
Two standard doses of MenACWY vaccine 4-6 weeks apart
BIOLOGICALChAdOx1 nCoV-19 (qPCR)
A single dose of 5x10\^10vp of ChAdOx1 nCoV-19 measured by qPCR
BIOLOGICALChAdOx1 nCoV-19 0.5mL prime plus boost
Two dose ChAdOx1 nCoV-19 0.5mL (3.5 - 6.5 × 10\^10 vp Abs 260)
BIOLOGICALTwo dose MenACWY vaccine min. 4 weeks apart
Two standard doses of MenACWY vaccine minimum 4 weeks apart
BIOLOGICALTwo 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
BIOLOGICALTwo 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
Sponsors
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults | Study duration (12 months from last vaccination) | Occurrence of serious adverse events (SAEs) throughout the study duration. |
| Assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older. | Study duration (12 months from last vaccination) | Number of virologically confirmed (PCR or NAAT positive) symptomatic cases of COVID-19 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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) | 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 | 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 | 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 | 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 | 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 | 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 | Study duration (12 months from last vaccination) | Proportion of people diagnosed with severe Covid-19 disease (defined according to clinical severity scales) |
| 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 | 7 days post vaccination | Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination |
| Assess humoral immunogenicity of ChAdOx1 nCoV-19: seroconversion | 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) | 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 | 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 | 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) | 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) | 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 | 56 days post vaccination | Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination (seroconversion rates) |
| Assess humoral immunogenicity of ChAdOx1 nCoV-19: antibody quantification | 28 days post vaccination | Quantify antibodies against SARS-CoV-2 spike protein (seroconversion rates) |
| 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 | 7 days post vaccination | Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Immunology by virus neutralising antibody assays | 6 months | Virus neutralising antibody (NAb) assays against live and/or pseudotype SARS-CoV-2 virus |
| To assess immunological correlates of protection in relation to occurrence of COVID-19 disease in ChAdOx1 nCoV-19 recipients | 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 |
| Exploratory Immunology by flow cytometry | 6 months | Cell analysis by flow cytometry assays |
| Exploratory Immunology by functional antibody assays | 6 months | Functional antibody assays |
| Exploratory Immunology: anti-vector immunity | 6 months | Anti-vector immunity induced by 1 or 2 doses of ChAdOx1 nCoV-19 |
| Measure exposure to COVID-19 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
| 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 | 6 months | Relationship between nadir CD4 count vs vaccine immune responses |
| 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 | 6 months | Relationship between age at enrolment and vaccine immune response |
| Assess whether increasing age and or CD4 nadir are associated with a lack of immune response in HIV infected adults | 6 months | Immune responses to ChAdOx1 nCoV-19 (assessed as described above) |
| Assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in HIV infected adults | 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 |
| To assess Impact of vaccination on HIV reservoirs | Study duration (12 months from last vaccination) | Change in Total HIV DNA copies per million CD4 T cells |
Countries
United Kingdom
Outcome results
None listed