Investigating a vaccine against COVID-19
| ISRCTN | ISRCTN90906759 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN90906759 |
| EudraCT/CTIS number | 2020-001228-32 |
| IRAS number | 281904 |
| ClinicalTrials.gov number | NCT04400838 |
| Secondary identifying numbers | CPMS 45551, IRAS 281904 |
- Submission date
- 04/05/2020
- Registration date
- 07/05/2020
- Last edited
- 24/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
COVID-19 is a condition caused by the coronavirus (called SARS-CoV-2) that was first identified in late 2019. This virus can infect the respiratory (breathing) system. Some people do not have symptoms but can carry the virus and pass it on to others. People who have developed the condition may develop a fever and/or a continuous cough among other symptoms. This can develop into pneumonia. Pneumonia is a chest infection where the small air pockets of the lungs, called alveoli, fill with liquid and make it more difficult to breathe.
In 2020, the virus has spread to many countries around the world and neither a vaccine against the virus or specific treatment for COVID-19 has yet been developed. As of March 2020, it is advised that people minimize travel and social contact, and regularly wash their hands to reduce the spread of the virus.
Groups who are at a higher risk from infection with the virus, and therefore of developing COVID-19, include people aged over 70 years, people who have long-term health conditions (such as asthma or diabetes), people who have a weakened immune system and people who are pregnant. People in these groups, and people who might come into contact with them, can reduce this risk by following the up-to-date advice to reduce the spread of the virus.
The WHO declared the COVID-19 epidemic a Public Health Emergency of International Concern on 30th January 2020. There are no currently licensed vaccines or specific treatments for COVID-19. Vaccines are the most cost-effective way of controlling outbreaks and the international community have stepped-up their efforts towards developing one against COVID-19.
The aim of this study is to assess whether healthy people can be protected from COVID-19 with a new vaccine called ChAdOx1 nCoV-19. It will also provide valuable information on the safety of the vaccine and its ability to generate good immune responses against the virus. The researchers will do this by randomly allocating participants to receive the investigational vaccine or a MenACWY vaccine in addition to doing blood tests and collecting information about any symptoms that occur after vaccination.
Who can participate?
Healthy adults aged 18 years and older. Participation in this study is voluntary but the researchers are only accepting volunteers from the local area around the study sites.
What does the study involve?
Participants will be randomly allocated to receive the investigational vaccine or a MenACWY vaccine. The researchers will then do blood tests and collect information about any symptoms that occur after vaccination. Dependent on the group, there will be between six and twelve study visits over a 12-month period. Participants will be asked to complete a diary for up to 28 days after the vaccination and will be closely monitored by the study team.
What are the possible benefits and risks of participating?
Knowledge gained from this study will help researchers to develop a vaccine against the newly emerging coronavirus disease COVID-19. There are no direct benefits of taking part, however, participants will receive a full medical examination as part of the study. Although this is the first time this vaccine has been administered to humans, similar investigational vaccines have been widely administered for many pathologies without significant safety concerns. Drawing blood may cause slight pain and occasionally bruising. Common side effects of vaccinations are some mild redness and swelling at the injection site. Participants may feel like they have flu-like symptoms within 24 hours of the vaccinations. These usually resolve within 48 hours.
Where is the study run from?
Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital (UK)
When is the study starting and how long is it expected to run for?
March 2020 to December 2024
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Emma Plested, covid19@ndm.ox.ac.uk
Contact information
Scientific
Oxford Vaccine Centre
Centre for Clinical Vaccinology & Tropical Medicine
University of Oxford
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
| covid19@ndm.ox.ac.uk |
Study information
| Study design | Single-blind randomized safety and efficacy study, with immunogenicity sub-studies in older and younger age groups |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | ISRCTN90906759_PIS(group 4)_v2.0_14Apr20.pdf |
| Scientific title | A phase II/III study to determine the efficacy, safety and immunogenicity of the candidate coronavirus disease (COVID-19) vaccine ChAdOx1 nCoV-19 |
| Study acronym | COV002 |
| Study hypothesis | Current objectives as of 28/09/2020: 1. To assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older 2. To assess the safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19 3. To assess the efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 4. To assess the humoral immunogenicity of ChAdOx1 nCoV-19 5. To assess the cellular immunity of ChAdOx1 nCoV-19 in older adults and in children (groups 1, 2, 3, 7 and 8 only) 6. To 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) Previous objectives: 1. To assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older 2. To assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults and children |
| Ethics approval(s) | Approved 08/04/2020, South Central - Berkshire Research Ethics Committee (Level 3, Block B, Whitefriars, Lewins Mead, Bristol, BS1 2NT, UK; +44 (0)2071048046; berkshire.rec@hra.nhs.uk), REC ref: 20/SC/0179 |
| Condition | COVID-19 (SARS-CoV-2 infection) |
| Intervention | Current intervention as of 21/04/2021 (see additional files for previous interventions prior to 04/12/2020): Group 1 80 participants aged 56-69 years will receive either single-dose ChAdOx1 nCoV-19 5x10(10) virus particles (vp) (Abs 260) or MenACWY at day 0, or two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime followed by 2.2x10(10) (qPCR) boost or two-dose MenACWY (4-6 weeks apart), then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. All group 1 volunteers that were originally randomised to single-dose subgroups will now be offered a booster vaccination. Once boosted, these remaining volunteers will instead be followed up on a schedule relative to the boost dose which will be POST BOOST+28 days, POST BOOST +90, POST BOOST +182 and POST BOOST +364 days. Group 2 120 participants aged 70 years or older will receive ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) or MenACWY at day 0, or two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime followed by 2.2x10(10) (qPCR) boost or two-dose MenACWY (4-6 weeks apart), then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. All group 2 volunteers that were originally randomised to single-dose subgroups will now be offered a booster vaccination. Once boosted, these remaining volunteers will instead be followed up on a schedule relative to the boost dose which will be POST BOOST+28 days, POST BOOST +90, POST BOOST +182 and POST BOOST +364 days. Group 4 Up to 3550 participants aged 18-55 years will receive either single-dose ChAdOx1 nCoV-19 5x10(10) virus particles (vp) (Abs 260) or MenACWY at day 0, or two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime followed by 2.2x10(10) (qPCR) boost or two-dose MenACWY (4-12 weeks apart, +2 weeks), then followed up at days 28, 90, 182 and 364. Two dose subgroups will have additional visits at day 42 and 56. A further prime/boost subgroup will receive a two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime and 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) boost or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) boost at day 0 and day 28, respectively, or two-dose MenACWY, (4-12 weeks apart, +2 weeks). The booster subgroup will be further followed up at days 28, 90, 182 and 365 after booster. Group 5 Up to 230 participants aged 18-55 will receive ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY at day 0 or two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) or ChAdOx1 nCoV-19 (Covishield 0.9x1011 vp/ml, 0.25ml prime and 0.5ml boost), or two-dose MenACWY, (4-6 weeks apart) then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at day 31, 35 and 42. All group 5a volunteers that were originally randomised to single-dose subgroups will now be offered a booster vaccination. Once boosted, these remaining volunteers will instead be followed up on a schedule relative to the boost dose which will be POST BOOST+28 days, POST BOOST +90, POST BOOST +182 and POST BOOST +364 days. Group 6 Up to 6000 participants aged 18-55 years will receive ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY at day 0 or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) prime and 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) boost or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) boost or two-dose MenACWY, (4-12 weeks apart, +2 weeks), then followed up at days 28, 90, 182 and 364. Two dose subgroups will have additional visits at day 42 and 56. Booster subgroup will be further followed up at days 28, 90, 182 and 365 after booster. Group 7 80 participants aged 56-69 years will receive either single dose ChAdOx1 nCoV-19 5x10(10) virus particles (vp) (qPCR) or single dose MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY (4-6 weeks apart), then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. Group 8 120 participants aged 70 years or older will receive single dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or single dose MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) prime and (3.5 – 6.5 × 1010 vp, Abs 260, corrected for PS80) boost OR ChAdOx1 nCoV-19 5x1010vp (qPCR) boost (4-6 weeks apart), OR two-dose MenACWY (4-6 weeks apart) then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. Group 9 Approximately 1000 participants aged 56-69 will receive two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp, (Abs 260, corrected for PS80) or two-dose MenACWY (4-6 weeks apart), then followed up at days 28, 56, 118, 210 and 364. Group 10 Approximately 1000 participants aged 70 years and over will receive two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp, (Abs 260, corrected for PS80) or two-dose MenACWY (4-6 weeks apart), then followed up at days 28, 56, 118, 210 and 364. Group 11 Up to 60 participants aged 18-55 who previously received a ChAdOx1 vectored vaccine will receive two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) (4-6 weeks apart), then followed up at days 14, 28, 56, 118, 210 and 364. Group 12 Up to 60 HIV infected individuals aged 18-55 will receive two dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) at day 0 and day 28, then followed up at days 3, 7, 14, 28, 31, 35, 42, 56, 182 and 364. Volunteers will stay in the trial site for observation for a minimum of 15 minutes (+15 minutes), in case of immediate adverse events. In groups 1-3, 5, 7, 8, 11 and 12 and in a subset of volunteers in groups 4,6, 9 and 10 (n=1000, each groups 4 and 6 and up to 500 in each of groups 9 and 10), participants will be given an oral thermometer, tape measure and diary card (paper or electronic), with instructions on use. All participants will be given the emergency 24-hour telephone number to contact the on-call study physician if needed. Safety will be assessed in real time. The DSMB will periodically assess safety and efficacy data every 4-8 weeks and/or as required. Participants will be followed over the duration of the study to record adverse events and episodes of virologically confirmed symptomatic COVID-19 cases. Participants will be tested for COVID-19 if they present with a new onset of fever OR cough OR shortness of breath. All study participants (that remain blinded) will be unblinded. Following this, control participants aged 30 and above will be offered ChAdOx1 nCoV-19 in the approved MHRA 4-to-12 week, 2-dose schedule. Participants will remain enrolled in the study and continue the follow up visit schedule listed for their sub-group concurrently with the provision of treatment prime and boost visits. Due to the updated guidance relating to the emerging association of thrombosis with thrombocytopenia and ChAdOx1 nCoV-19, trial participants aged 29 and under will not be offered (prime) vaccinations with ChAdOx1 nCoV-19. These individuals will instead be advised to await vaccination under the national rollout program. _____ Previous intervention as of 04/12/2020 (see additional files for previous interventions): Group 1 80 participants aged 56-69 years will receive either single-dose ChAdOx1 nCoV-19 5x10(10) virus particles (vp) (Abs 260) or MenACWY at day 0, or two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime followed by 2.2x10(10) (qPCR) boost or two-dose MenACWY (4-6 weeks apart), then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. All group 1 volunteers that were originally randomised to single-dose subgroups will now be offered a booster vaccination. Once boosted, these remaining volunteers will instead be followed up on a schedule relative to the boost dose which will be POST BOOST+28 days, POST BOOST +90, POST BOOST +182 and POST BOOST +364 days. Group 2 120 participants aged 70 years or older will receive ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) or MenACWY at day 0, or two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime followed by 2.2x10(10) (qPCR) boost or two-dose MenACWY (4-6 weeks apart), then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. All group 2 volunteers that were originally randomised to single-dose subgroups will now be offered a booster vaccination. Once boosted, these remaining volunteers will instead be followed up on a schedule relative to the boost dose which will be POST BOOST+28 days, POST BOOST +90, POST BOOST +182 and POST BOOST +364 days. Group 4 Up to 3550 participants aged 18-55 years will receive either single-dose ChAdOx1 nCoV-19 5x10(10) virus particles (vp) (Abs 260) or MenACWY at day 0, or two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime followed by 2.2x10(10) (qPCR) boost or two-dose MenACWY (4-12 weeks apart, +2 weeks), then followed up at days 28, 90, 182 and 364. Two dose subgroups will have additional visits at day 42 and 56. A further prime/boost subgroup will receive a two-dose ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) prime and 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) boost or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) boost at day 0 and day 28, respectively, or two-dose MenACWY, (4-12 weeks apart, +2 weeks). The booster subgroup will be further followed up at days 28, 90, 182 and 365 after booster. Group 5 Up to 230 participants aged 18-55 will receive ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY at day 0 or two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) or ChAdOx1 nCoV-19 (Covishield 0.9x1011 vp/ml, 0.25ml prime and 0.5ml boost), or two-dose MenACWY, (4-6 weeks apart) then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at day 31, 35 and 42. All group 5a volunteers that were originally randomised to single-dose subgroups will now be offered a booster vaccination. Once boosted, these remaining volunteers will instead be followed up on a schedule relative to the boost dose which will be POST BOOST+28 days, POST BOOST +90, POST BOOST +182 and POST BOOST +364 days. Group 6 Up to 6000 participants aged 18-55 years will receive ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY at day 0 or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) prime and 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) boost or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) boost or two-dose MenACWY, (4-12 weeks apart, +2 weeks), then followed up at days 28, 90, 182 and 364. Two dose subgroups will have additional visits at day 42 and 56. Booster subgroup will be further followed up at days 28, 90, 182 and 365 after booster. Group 7 80 participants aged 56-69 years will receive either single dose ChAdOx1 nCoV-19 5x10(10) virus particles (vp) (qPCR) or single dose MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY (4-6 weeks apart), then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. Group 8 120 participants aged 70 years or older will receive single dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or single dose MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) prime and (3.5 – 6.5 × 1010 vp, Abs 260, corrected for PS80) boost OR ChAdOx1 nCoV-19 5x1010vp (qPCR) boost (4-6 weeks apart), OR two-dose MenACWY (4-6 weeks apart) then followed up at days 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at days 31, 35 and 42. Group 9 Approximately 1000 participants aged 56-69 will receive two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp, (Abs 260, corrected for PS80) or two-dose MenACWY (4-6 weeks apart), then followed up at days 28, 56, 118, 210 and 364. Group 10 Approximately 1000 participants aged 70 years and over will receive two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp, (Abs 260, corrected for PS80) or two-dose MenACWY (4-6 weeks apart), then followed up at days 28, 56, 118, 210 and 364. Group 11 Up to 60 participants aged 18-55 who previously received a ChAdOx1 vectored vaccine will receive two-dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) (4-6 weeks apart), then followed up at days 14, 28, 56, 118, 210 and 364. Group 12 Up to 60 HIV infected individuals aged 18-55 will receive two dose ChAdOx1 nCoV-19 3.5 – 6.5 × 10(10) vp (Abs 260, corrected for PS80) at day 0 and day 28, then followed up at days 3, 7, 14, 28, 31, 35, 42, 56, 182 and 364. Volunteers will stay in the trial site for observation for a minimum of 15 minutes (+15 minutes), in case of immediate adverse events. In groups 1-3, 5, 7, 8, 11 and 12 and in a subset of volunteers in groups 4,6, 9 and 10 (n=1000, each groups 4 and 6 and up to 500 in each of groups 9 and 10), participants will be given an oral thermometer, tape measure and diary card (paper or electronic), with instructions on use. All participants will be given the emergency 24-hour telephone number to contact the on-call study physician if needed. Safety will be assessed in real time. The DSMB will periodically assess safety and efficacy data every 4-8 weeks and/or as required. Participants will be followed over the duration of the study to record adverse events and episodes of virologically confirmed symptomatic COVID-19 cases. Participants will be tested for COVID-19 if they present with a new onset of fever OR cough OR shortness of breath. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase II/III |
| Drug / device / biological / vaccine name(s) | ChAdOx1-nCoV19, MenACWY |
| Primary outcome measure | Current primary outcome measure as of 17/11/2020: 1. Efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older measured by virologically confirmed (PCR* positive) symptomatic cases of COVID-19. 2. Safety of the candidate vaccine ChAdOx1 nCoV-19 in adults and children measured by recording the occurrence of serious adverse events (SAEs) throughout the study duration. * Or other nucleic acid amplification test (NAAT) _____ Previous primary outcome measure as of 30/07/2020: 1. Efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older measured by virologically confirmed (PCR positive) symptomatic cases of COVID-19 2. Safety of the candidate vaccine ChAdOx1 nCoV-19 in adults and children measured by recording the occurrence of serious adverse events (SAEs) over the course of 6 months _____ Previous primary outcome measure: 1. Efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older measured by virologically confirmed (PCR positive) symptomatic cases of COVID-19 over the course of 6 months 2. Safety of the candidate vaccine ChAdOx1 nCoV-19 in adults and children measured by recording the occurrence of serious adverse events (SAEs) over the course of 6 months |
| Secondary outcome measures | Current secondary outcome measures as of 28/09/2020: 1. Safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: 1.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination 1.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination 1.3. Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination 1.4. Change from baseline for safety laboratory measures (except groups 4, 6, 9 and 10) 1.5. Occurrence of disease enhancement episodes 2. Efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 over the course of 6 months: 2.1. Hospital admissions associated with COVID-19 2.2. Intensive care unit (ICU) admissions associated with COVID-19 2.3. Deaths associated with COVID-19 2.4. Seroconversion against non-Spike SARS-CoV-2 antigens 2.5. Severe COVID-19 disease (defined according to clinical severity scales) 3. Cellular and humoral immunogenicity of ChAdOx1 nCoV-19 over the course of 6 months: 3.1. Antibodies against SARS-CoV-2 spike protein (seroconversion rates) at Day 28 post-vaccination 3.2. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination 3.3. Cellular immunity of ChAdOx1 nCoV-19 in older adults and in children (groups 1, 2, 3, 7 and 8 only) 3.4. Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein 4. 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): 4.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination 4.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination 4.3. Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination 4.4. Change from baseline and change from pre-booster for safety laboratory measures 4.5. Occurrence of disease enhancement episodes over the course of 6 months 4.6. Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination 4.7. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination ______ Previous secondary outcome measures from 15/06/2020 to 28/09/2020: 1. Safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: 1.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination 1.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination 1.3. Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination (except group 4 and 6) 1.4. Change from baseline for safety laboratory measures (except group 4 and 6) 1.5. Occurrence of disease enhancement episodes 2. Efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 over the course of 6 months: 2.1. Hospital admissions associated with COVID-19 2.2. Intensive care unit (ICU) admissions associated with COVID-19 2.3. Deaths associated with COVID-19 2.4. Seroconversion against non-Spike SARS-CoV-2 antigens 3. Cellular and humoral immunogenicity of ChAdOx1 nCoV-19 over the course of 6 months: 3.1. Antibodies against SARS-CoV-2 spike protein (seroconversion rates) at Day 28 post-vaccination 3.2. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination 3.3. Cellular immunity of ChAdOx1 nCoV-19 in older adults and in children (groups 1, 2 and 3 only) 3.4. Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein 4. 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): 4.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination 4.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination 4.3. Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination 4.4. Change from baseline and change from pre-booster for safety laboratory measures 4.5. Occurrence of disease enhancement episodes over the course of 6 months 4.6. Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination 4.7. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination ______ Previous secondary outcome measures as of 22/05/2020: 1. Safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: 1.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination 1.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination 1.3. Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination (except group 4) 1.4. Change from baseline for safety laboratory measures (except group 4) 1.5. Occurrence of disease enhancement episodes 2. Efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 over the course of 6 months: 2.1. Hospital admissions associated with COVID-19 2.2. Intensive care unit (ICU) admissions associated with COVID-19 2.3. Deaths associated with COVID-19 2.4. Seroconversion against non-Spike SARS-CoV-2 antigens 3. Cellular and humoral immunogenicity of ChAdOx1 nCoV-19 over the course of 6 months: 3.1. Antibodies against SARS-CoV-2 spike protein (seroconversion rates) at Day 28 post-vaccination 3.2. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination 3.3. Cellular immunity of ChAdOx1 nCoV-19 in older adults and in children (groups 1, 2 and 3 only) 3.4. Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein 4. 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): 4.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination 4.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination 4.3. Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination 4.4. Change from baseline and change from pre-booster for safety laboratory measures 4.5. Occurrence of disease enhancement episodes over the course of 6 months 4.6. Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination 4.7. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination ______ Previous secondary outcome measures: 1. Safety, tolerability and reactogenicity profile of the candidate vaccine ChAdOx1 nCoV-19: 1.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following vaccination 1.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following vaccination 1.3. Occurrence of unsolicited adverse events (AEs) for 28 days following vaccination 1.4. Change from baseline for safety laboratory measures over the course of 6 months 1.5. Occurrence of disease enhancement episodes 2. Efficacy of the candidate ChAdOx1 nCoV-19 against severe and non-severe COVID-19 over the course of 6 months: 2.1. Hospital admissions associated with COVID-19 2.2. Intensive care unit (ICU) admissions associated with COVID-19 2.3. Deaths associated with COVID-19 2.4. Seroconversion against non-Spike SARS-CoV-2 antigens 3. Cellular and humoral immunogenicity of ChAdOx1 nCoV-19 over the course of 6 months: 3.1. Antibodies against SARS-CoV-2 spike protein (seroconversion rates) at Day 28 post-vaccination 3.2. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 28 post-vaccination 3.3. Cellular immunity of ChAdOx1 nCoV-19 in older adults and in children (groups 1, 2 and 3 only) 3.4. Interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISpot) responses to SARS-CoV-2 spike protein 4. 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): 4.1. Occurrence of solicited local reactogenicity signs and symptoms for 7 days following booster vaccination 4.2. Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following booster vaccination 4.3. Occurrence of unsolicited adverse events (AEs) for 28 days following booster vaccination 4.4. Change from pre-booster for safety laboratory measures 4.5. Occurrence of disease enhancement episodes over the course of 6 months 4.6. Antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination 4.7. Proportion of seroconversion to antibodies against SARS-CoV-2 spike protein at Day 56 post-vaccination |
| Overall study start date | 02/03/2020 |
| Overall study end date | 31/12/2024 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 55 Years |
| Sex | Both |
| Target number of participants | Approximately 12,390 participants |
| Participant inclusion criteria | Current inclusion criteria as of 04/12/2020 (see additional files for previous interventions): 1. Adults aged 18-55 years (groups 4, 5, 6 and 11) 2. Adults aged 56-69 years (groups 1, 7 and 9) 3. Adults aged 70 years and older (groups 2, 8 and 10) 4. Able and willing (in the Investigator’s opinion) to comply with all study requirements 5. 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 6. 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 7. Agreement to refrain from blood donation during the course of the study 8. Provide written informed consent Additional Inclusion criteria for Group 12 (HIV sub-study): 1. HIV positive 2. Receiving antiretroviral therapy 3. Undetectable HIV viral load 4. CD4 >350 cells/ml |
| Participant exclusion criteria | Current exclusion criteria as of 21/10/2020 (see additional files for previous interventions): 1. 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 2. 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 3. 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 4. 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. 5. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate 6. 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) 7. History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY 8. Any history of angioedema 9. Any history of anaphylaxis 10. Pregnancy, lactation or willingness/intention to become pregnant during the study 11. Current diagnosis of or treatment for cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) 12. History of serious psychiatric condition likely to affect participation in the study 13. Bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture 14: Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 15. Suspected or known current alcohol or drug dependency 16. 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 17. 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) 18. History of laboratory-confirmed COVID-19 (except groups 5d, 9, 10 and 11). 18.1 Seropositivity to SARS-CoV-2 before enrolment (except groups 5d, 9 and,10 and 11) Additional exclusion criteria for Groups 4, 6, 9 and 10: 19. 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 Additional exclusion criteria for Group 3: 20. Chronic medical conditions such as chronic lung disease, chronic liver disease, chronic renal failure, chronic heart disease, congenital genetic syndromes (e.g. Trisomy 21) 21. Fulfil any of the contraindications to vaccination as specified in The Green Book NB: volunteers with previous PCR-positive results are also allowed in groups 9, 10 and 11 |
| Recruitment start date | 28/05/2020 |
| Recruitment end date | 30/09/2020 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
Southampton
SO16 6YD
United Kingdom
Hammersmith Hospital, Imperial College NHS Trust
150 Du Cane Road
London
W12 0HS
United Kingdom
Tooting
London
SW17 0TQ
United Kingdom
Bristol
BS1 3NU
United Kingdom
Southmead Road
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom
University Park
Nottingham
NG7 2QW
United Kingdom
Glossop Road
Sheffield
S10 2RX
United Kingdom
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
St. Cadoc’s Hospital, Lodge Road, Caerleon
Newport
NP18 3XQ
United Kingdom
J B Russell House Gartnavel Royal Hospital Campus
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
St Thomas Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
1 Daulby Street
Liverpool
L7 8XZ
United Kingdom
Newcastle upon Tyne
NE1 4LP
United Kingdom
London
NW1 2PG
United Kingdom
Crewe Rd
Edinburgh
EH4 2XU
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
South Block
Queen's Medical Centre Campus
Derby Road
Nottingham
NG7 2UH
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom
Sponsor information
University/education
Joint Research Office
1st floor
Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865 616480 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
Funders
Funder type
Research organisation
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/10/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | There are no plans currently to have any additional documents be available. Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version v2.0 | 14/04/2020 | 07/05/2020 | No | Yes |
| Participant information sheet | version v2.0 | 14/04/2020 | 07/05/2020 | No | Yes |
| Participant information sheet | version v2.0 | 14/04/2020 | 07/05/2020 | No | Yes |
| Participant information sheet | version v3.0 | 13/05/2020 | 22/05/2020 | No | Yes |
| Participant information sheet | version V4.0 | 26/05/2020 | 04/06/2020 | No | Yes |
| Participant information sheet | version V2.0 | 26/05/2020 | 04/06/2020 | No | Yes |
| Participant information sheet | version V2.0 | 26/05/2020 | 04/06/2020 | No | Yes |
| Participant information sheet | version V2.0 | 26/05/2020 | 04/06/2020 | No | Yes |
| Participant information sheet | version V4.0 | 08/06/2020 | 15/06/2020 | No | Yes |
| Participant information sheet | version V4.0 | 08/06/2020 | 15/06/2020 | No | Yes |
| Participant information sheet | version V4.0 | 08/06/2020 | 15/06/2020 | No | Yes |
| Participant information sheet | version V4.0 | 08/06/2020 | 15/06/2020 | No | Yes |
| Participant information sheet | version V6.0 | 18/06/2020 | 24/06/2020 | No | Yes |
| Participant information sheet | version V5.0 | 18/06/2020 | 24/06/2020 | No | Yes |
| Participant information sheet | version V5.0 | 18/06/2020 | 24/06/2020 | No | Yes |
| Participant information sheet | version V5.0 | 18/06/2020 | 24/06/2020 | No | Yes |
| Participant information sheet | version V8.0 | 12/07/2020 | 17/07/2020 | No | Yes |
| Participant information sheet | version V8.0 | 12/07/2020 | 17/07/2020 | No | Yes |
| Participant information sheet | version V8.0 | 12/07/2020 | 17/07/2020 | No | Yes |
| Participant information sheet | version V9.0 | 20/07/2020 | 30/07/2020 | No | Yes |
| Participant information sheet | version V9.0 | 20/07/2020 | 30/07/2020 | No | Yes |
| Participant information sheet | version V9.0 | 20/07/2020 | 30/07/2020 | No | Yes |
| Participant information sheet | version V10.0 | 05/08/2020 | 25/08/2020 | No | Yes |
| Participant information sheet | version V10.0 | 05/08/2020 | 25/08/2020 | No | Yes |
| Participant information sheet | version V10.0 | 05/08/2020 | 25/08/2020 | No | Yes |
| Participant information sheet | version V11.0 | 11/09/2020 | 15/09/2020 | No | Yes |
| Participant information sheet | version V11.0 | 11/09/2020 | 15/09/2020 | No | Yes |
| Participant information sheet | version V11.0 | 11/09/2020 | 15/09/2020 | No | Yes |
| Other files | Previous inclusion and exclusion criteria | 28/09/2020 | No | No | |
| Participant information sheet | version V12.0 | 15/09/2020 | 28/09/2020 | No | Yes |
| Participant information sheet | version V12.0 | 15/09/2020 | 28/09/2020 | No | Yes |
| Participant information sheet | version V12.0 | 15/09/2020 | 28/09/2020 | No | Yes |
| Participant information sheet | version V13.0 | 14/10/2020 | 21/10/2020 | No | Yes |
| Participant information sheet | version V13.0 | 14/10/2020 | 21/10/2020 | No | Yes |
| Participant information sheet | version V13.0 | 14/10/2020 | 21/10/2020 | No | Yes |
| Results article | results | 19/12/2021 | 19/11/2020 | Yes | No |
| Other files | Previous inclusion and exclusion criteria | 04/12/2020 | No | No | |
| Participant information sheet | version V14.0 | 02/12/2020 | 04/12/2020 | No | Yes |
| Participant information sheet | version V14.0 | 02/12/2020 | 04/12/2020 | No | Yes |
| Participant information sheet | version V14.0 | 02/12/2020 | 04/12/2020 | No | Yes |
| Interim results article | interim results | 09/01/2021 | 09/12/2020 | Yes | No |
| Participant information sheet | version V15.0 | 10/12/2020 | 14/12/2020 | No | Yes |
| Participant information sheet | version V15.0 | 10/12/2020 | 14/12/2020 | No | Yes |
| Participant information sheet | version V15.0 | 10/12/2020 | 14/12/2020 | No | Yes |
| Results article | results | 06/03/2021 | 23/02/2021 | Yes | No |
| Participant information sheet | version V16.0 | 01/03/2021 | 10/03/2021 | No | Yes |
| Participant information sheet | version V16.0 | 01/03/2021 | 10/03/2021 | No | Yes |
| Participant information sheet | version V16.0 | 01/03/2021 | 10/03/2021 | No | Yes |
| Participant information sheet | version 17.0 | 09/04/2021 | 21/04/2021 | No | Yes |
| Participant information sheet | version 17.0 | 09/04/2021 | 21/04/2021 | No | Yes |
| Participant information sheet | version 4.0 | 09/04/2021 | 21/04/2021 | No | Yes |
| Participant information sheet | version 17.0 | 09/04/2021 | 21/04/2021 | No | Yes |
| Participant information sheet | version 4.1 | 14/05/2021 | 24/05/2021 | No | Yes |
| Participant information sheet | version 17.1 | 14/05/2021 | 24/05/2021 | No | Yes |
| Participant information sheet | version 17.1 | 14/05/2021 | 24/05/2021 | No | Yes |
| Participant information sheet | version 17.1 | 14/05/2021 | 24/05/2021 | No | Yes |
| Participant information sheet | version 5 | 12/08/2021 | 02/09/2021 | No | Yes |
| Participant information sheet | version 18 | 12/08/2021 | 02/09/2021 | No | Yes |
| Participant information sheet | version 18 | 12/08/2021 | 02/09/2021 | No | Yes |
| Participant information sheet | version 18 | 12/08/2021 | 02/09/2021 | No | Yes |
| Interim results article | Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK | 01/09/2021 | 06/09/2021 | Yes | No |
| Participant information sheet | Group 12 version 6.0 |
14/10/2021 | No | Yes | |
| Results article | 29/06/2022 | 04/07/2022 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 22.2 | 26/06/2023 | 01/08/2023 | No | No |
| Protocol file | version 22.3 | 27/03/2024 | 24/04/2024 | No | No |
Additional files
- ISRCTN90906759_PIS(group 1_2)_v2.0_14Apr20.pdf
- Uploaded 07/05/2020
- ISRCTN90906759_PIS(group 3)_v2.0_ 14Apr20.pdf
- Uploaded 07/05/2020
- ISRCTN90906759_PIS(group 4)_v2.0_14Apr20.pdf
- Uploaded 07/05/2020
- ISRCTN90906759_PIS_(group 3)_v3.0_13May2020.pdf
- uploaded 22/05/2020
- ISRCTN90906759 PIS ages 70 years and over V2.0 26 May 2020.pdf
- uploaded 04/06/2020
- ISRCTN90906759 PIS ages 56 - 69 years V2.0 26 May 2020.pdf
- uploaded 04/06/2020
- ISRCTN90906759 PIS ages 18 - 55 years V2.0 26 May 2020.pdf
- uploaded 04/06/2020
- ISRCTN90906759 PIS (group 3) V4.0 26 May 2020.pdf
- uploaded 04/06/2020
- ISRCTN90906759 PIS V4.0 Cover letter 8Jun2020.pdf
- uploaded 15/06/2020
- ISRCTN90906759 PIS ages 18 - 55 years V4.0 08Jun20.pdf
- uploaded 15/06/2020
- ISRCTN90906759 PIS ages 56 - 69 years V4.0 08Jun20.pdf
- uploaded 15/06/2020
- ISRCTN90906759 PIS ages 70 years and over V4.0 08Jun20.pdf
- uploaded 15/06/2020
- ISRCTN90906759_PIS ages 70 years and over_V5.0_18Jun20.pdf
- Uploaded 24/06/2020
- ISRCTN90906759_PIS ages 18 - 55 years_V5.0_18Jun20.pdf
- Uploaded 24/06/2020
- ISRCTN90906759_PIS ages 56 - 69 years_V5.0_18Jun20.pdf
- Uploaded 24/06/2020
- ISRCTN90906759_PIS(group 3)_V6.0_18Jun20.pdf
- Uploaded 24/06/2020
- ISRCTN90906759 PIS ages 70 years and over V8.0 12Jul2020.pdf
- uploaded 17/07/2020
- ISRCTN90906759 PIS ages 56 - 69 years V8.0 12Jul2020.pdf
- uploaded 17/07/2020
- ISRCTN90906759 PIS ages 18 - 55 years V8.0 12Jul2020.pdf
- uploaded 17/07/2020
- ISRCTN90906759 PIS ages 70 years and over V9.0 20Jul20.pdf
- uploaded 30/07/2020
- ISRCTN90906759 PIS ages 56 - 69 years V9.0 20Jul20.pdf
- uploaded 30/07/2020
- ISRCTN90906759 PIS ages 18 - 55 years V9.0 20Jul20.pdf
- uploaded 30/07/2020
- ISRCTN90906759_PIS_ages56 - 69 years_V10.0 05Aug2020_non-localiased.pdf
- uploaded 25/08/2020
- ISRCTN90906759_PIS_ages18 - 55 years_V10.0_05Aug2020_non-localised.pdf
- uploaded 25/08/2020
- ISRCTN90906759_PIS_ages 70 years and over_V10.0_05Aug2020_non-localised.pdf
- uploaded 25/08/2020
- ISRCTN90906759_PIS_ages 18-55years_V11.0_11Sep20_non-localised.pdf
- Uploaded 15/09/2020
- ISRCTN90906759_PIS_ages56-69 years_V11.0_11Sep20_non-localised.pdf
- Uploaded 15/09/2020
- ISRCTN90906759_PIS_ages70yearsandover_V11.0_11Sep20_non-localised.pdf
- Uploaded 15/09/2020
- ISRCTN90906759_PIS_ages 56 - 69 years_V12.0_15Sep20.pdf
- Uploaded 28/09/2020
- ISRCTN90906759_PIS_ages 18 - 55 years_V12.0_15Sep20.pdf
- Uploaded 28/09/2020
- ISRCTN90906759 _PIS ages 70 years and over_V12.0_15Sep20.pdf
- Uploaded 28/09/2020
- ISRCTN90906759_Previous inclusion and exclusion criteria.docx
- Uploaded 28/09/2020
- ISRCTN90906759_PIS ages 18 - 55 years V13.0_14Oct2020_non-localised.pdf
- uploaded 21/10/2020
- ISRCTN90906759_PIS ages 56 - 69 years V13.0_14Oct2020_non-localised.pdf
- uploaded 21/10/2020
- ISRCTN90906759_PIS ages 70 years and over V13.0_14Oct2020_non-localised.pdf
- uploaded 21/10/2020
- ISRCTN90906759_PIS ages 18 - 55 years_V14.0_02Dec2020.pdf
- uploaded 04/12/2020
- ISRCTN90906759_PIS ages 56 - 69 years_V14.0_02Dec2020.pdf
- uploaded 04/12/2020
- ISRCTN90906759_PIS ages 70 years and over_V14.0_02Dec2020.pdf
- uploaded 04/12/2020
- ISRCTN90906759_Previous inclusion and exclusion criteria.docx
- uploaded 04/12/2020
- ISRCTN90906759_PIS ages 18 - 55 years_V15.0_10Dec2020.pdf
- Uploaded 14/12/2020
- ISRCTN90906759_PIS ages 56 - 69 years_V15.0_10Dec2020.pdf
- Uploaded 14/12/2020
- ISRCTN90906759_PIS ages 70 years and over_V15.0_10Dec2020.pdf
- Uploaded 14/12/2020
- ISRCTN9096759_PIS ages 70 years and over_V16.0_01Mar2021_non-localised.pdf
- uploaded 10/03/2021
- ISRCTN9095759_PIS ages 56 - 69 years_V16.0_01Mar2021_non-localised.pdf
- uploaded 10/03/2021
- ISRCTN9096759_PIS ages 18 - 55 years V16.0_01Mar2021_non-localised.pdf
- uploaded 10/03/2021
- ISRCTN90906759_PIS ages 18 - 55 years_V17.0_09Apr2021.pdf
- Uploaded 21/04/2021
- ISRCTN90906759_PIS ages 56 - 69 years_V17.0_09Apr2021.pdf
- Uploaded 21/04/2021
- ISRCTN90906759_PIS ages 70 years and over_V17.0_09Apr2021.pdf
- Uploaded 21/04/2021
- ISRCTN90906759_PIS Group 12_V4.0_09Apr2021.pdf
- Uploaded 21/04/2021
- ISRCTN90906759 PIS ages 70 years and over V17.1 14 May 2021_non localised.pdf
- uploaded 24/05/2021
- ISRCTN90906759 PIS ages 56 - 69 years V17.1 14 May 2021_non localised.pdf
- uploaded 24/05/2021
- ISRCTN90906759 PIS ages 18 - 55 years V17.1 14 May 2021_non localised.pdf
- uploaded 24/05/2021
- ISRCTN90906759 PIS Group 12 V4.1 14 May 2021_ non localised.pdf
- uploaded 24/05/2021
- 38245 COV002 PIS Group 12 V5.0 12August2021 non localised.pdf
- 38245 COV002 PIS ages 70 years and over V18 12Aug2021 non localised.pdf
- 38245 COV002 PIS ages 56 - 69 years V18 12Aug2021 non localised.pdf
- 38245 COV002 PIS ages 18 - 55 years V18 12Aug2021 non localised.pdf
- 38245 COV002 PIS Group 12 V6.0 27September 2021 non-localised.pdf
- Group 12
- ISRCTN90906759_Protocol_v22.2_26Jun2023.pdf
- ISRCTN90906759 COV002_Protocol_v22.3_27Mar24.pdf
Editorial Notes
24/04/2024: The following changes were made to the trial record:
1. Uploaded protocol v22.3 (not peer-reviewed) as an additional file.
2. The overall end date was changed from 31/03/2024 to 31/12/2024.
01/08/2023: The following changes have been made:
1. Protocol file uploaded.
2. The overall study end date has been changed from 31/03/2023 to 31/03/2024 and the plain English summary updated accordingly.
04/07/2022: Publication reference added.
14/03/2022: The following changes were made to the trial record:
1. The overall end date was changed from 31/03/2022 to 31/03/2023.
2. The intention to publish date was changed from 30/09/2022 to 31/10/2023.
3. The plain English summary was updated to reflect these changes.
14/10/2021: The participant information sheet (Group 12 v6.0) was uploaded as an additional file.
07/09/2021: The following changes were made to the trial record:
1. The overall trial end date was changed from 30/09/2021 to 31/03/2022.
2. The intention to publish date was changed from 31/03/2022 to 30/09/2022.
06/09/2021: Publication reference added.
02/09/2021: The participant information sheets (v18) have been uploaded as additional files.
24/05/2021: The updated participant information sheets (v17.1) have been uploaded as additional files.
21/04/2021: The following changes have been made:
1. The intervention has been changed.
2. The participant information sheets (v17, dated 09/04/2021) were uploaded
10/03/2021: The participant information sheets (v16, dated 01/03/2021) were uploaded.
23/02/2021: Publication reference added.
14/12/2020: The participant information sheets dated 10/12/2020 were uploaded.
09/12/2020: Publication reference added.
04/12/2020: The following changes were made to the trial record:
1. The updated participant information sheets were uploaded.
2. The plain English summary was changed.
3. The interventions were changed.
4. The inclusion criteria were changed.
5. The previous inclusion criteria, exclusion criteria, and interventions were uploaded as an additional file.
23/11/2020: PubMed address added.
19/11/2020: Publication reference added.
17/11/2020: The primary outcome measure was changed.
11/11/2020: The following changes were made to the trial record:
1. The target number of participants was changed from Approximately 12,330 participants to Approximately 12,390 participants
2. The recruitment start date was changed from 11/05/2020 to 28/05/2020.
06/11/2020: The following changes were made to the trial record:
1. The interventions were changed.
2. The target number of participants was changed from Up to 12,330 participants to Approximately 12,330 participants.
21/10/2020: The following changes were made to the trial record:
1. The exclusion criteria were changed.
2. The updated participant information sheets were uploaded.
28/09/2020: The following changes were made to the trial record:
1. The updated participant information sheets were uploaded.
2. The interventions were updated.
3. The inclusion and exclusion criteria, secondary outcome measures and study hypothesis were updated.
4. The previous inclusion and exclusion criteria were uploaded as an additional file.
15/09/2020: The updated participant information sheets were uploaded.
25/08/2020: The following changes were made to the trial record:
1. The updated participant information sheets were uploaded.
2. The interventions were changed.
3. The exclusion criteria were changed.
4. The previous inclusion and exclusion criteria were uploaded as an additional file.
04/08/2020: The interventions were changed.
30/07/2020: The following changes were made to the trial record:
1. The ClinicalTrials.gov number was added.
2. The interventions were changed.
3. The primary outcome measure was changed.
4. The inclusion criteria were changed.
5. The exclusion criteria were changed.
6. The previous inclusion and exclusion criteria were uploaded as an additional file.
7. The target number of participants was changed from "Up to 10,560 participants" to "Up to 12,330 participants".
8. The updated participant information sheets were uploaded.
21/07/2020: The previous inclusion and exclusion criteria have been removed from the main record and uploaded as an additional file.
17/07/2020: The updated participant information sheets were uploaded.
10/07/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/06/2020 to 30/09/2020.
2. The overall trial end date was changed from 30/06/2021 to 30/09/2021.
3. The intention to publish date was changed from 31/12/2021 to 31/03/2022.
24/06/2020: The following changes were made to the trial record:
1. The updated participant information sheets were uploaded.
2. The interventions were changed.
3. The inclusion criteria were changed.
4. The target number of participants was changed from 10,260 to 10,560.
15/06/2020: The following changes were made to the trial record:
1. The updated participant information sheets were uploaded.
2. The interventions were changed.
3. The secondary outcome measures were changed.
4. The inclusion criteria were changed.
5. The exclusion criteria were changed.
04/06/2020: The following changes were made to the trial record:
1. The updated participant information sheets were uploaded.
2. The interventions were changed.
3. The trial participating centres were updated (added: Oxford University Hospital Foundation Trust, Nottingham University Hospitals NHS Trust, Hull University Teaching Hospitals NHS Trust (HUTH), Northwick Park Hospital.
22/05/2020: The following changes were made to the trial record:
1. The updated participant information sheet (group 3) was uploaded.
2. The interventions were changed.
3. The secondary outcome measures were changed.
4. The inclusion criteria were changed.
5. The exclusion criteria were changed.
6. The target number of participants was changed from "3000 to 5260 participants" to "Up to 10,260 participants".
7. The trial participating centres "University of Nottingham Health Service, Sheffield Teaching Hospitals, University Hospitals Birmingham NHS Foundation Trust (UHB), Public Health Wales, Castle Hill Hospital, Greater Glasgow and Clyde NHS Board, Guy’s and St Thomas’ NHS Foundation Trust, Liverpool School of Tropical Medicine, The Newcastle upon Tyne Hospitals NHS Foundation Trust, UCLH, NHS Lothian, NIHR Cambridge Clinical Research Facility” were added.
8. The funder was changed from UK research and Innovation and Coalition for Epidemic Preparedness Innovations (CEPI) to National Institute for Health Research (NIHR).
9. The plain English summary was updated to reflect these changes.
11/05/2020: The scientific contact's details have been changed.
07/05/2020: The participant information sheets have been uploaded.
04/05/2020: Trial's existence confirmed by the NIHR.
