Plain English Summary
Current plain English summary as of 22/05/2020:
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 or older and children aged 5 - 12 years. 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 June 2021
Who is funding the study?
National Institute for Health Research (NIHR) (UK)
Who is the main contact?
Emma Plested, covid19@ndm.ox.ac.uk
_____
Previous 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 - 55 years and children aged 5 - 12 years. 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 five and nine study visits over a 12-month period. Participants will be asked to complete a diary for 7 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 June 2021
Who is funding the study?
UK Research and Innovation, Coalition for Epidemic Preparedness Innovations (CEPI)
Who is the main contact?
Emma Plested, covid19@ndm.ox.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Mrs Emma Plested
ORCID ID
Contact details
Oxford Vaccine Centre
Centre for Clinical Vaccinology & Tropical Medicine
University of Oxford
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
-
covid19@ndm.ox.ac.uk
Additional identifiers
EudraCT number
2020-001228-32
ClinicalTrials.gov number
Nil known
Protocol/serial number
CPMS 45551, IRAS 281904
Study information
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
Acronym
COV002
Study hypothesis
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
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
Study design
Single-blind randomised safety and efficacy study, with immunogenicity sub-studies in older and younger age groups
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Prevention
Patient information sheet
See additional files
Condition
COVID-19 (SARS-CoV-2 infection)
Intervention
Current interventions as of 24/06/2020:
Before vaccination, volunteers will be asked about their recent health to ensure that they are still medically fit. They will have blood tests taken and participants will be randomised (Groups 1 and 7: 3:1, Groups 2 and 8: 5:1, Groups 3-6: 1:1) to receive either ChAdOx1 nCoV-19 or MenACWY.
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 MenACWY at day 0 and day 28, 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 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 MenACWY at day 0 and day 28, 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 3
60 participants aged 5 to 12 years will receive ChAdOx1 nCoV-19 2.5x10(10) vp (qPCR) or MenACWY at day 0 and day 28, then followed up at days 3, 7, 28, 182 and 364
Group 4
Up to 4000 participants aged 18 years or older 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 MenACWY at day 0 and day 28, then followed up at days 28, 90, 182 and 364. Two dose subgroups will have additional visits at day 42 and 56.
Group 5
200 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, then followed up at days 3, 7, 14, 28, 56, 182 and 364
Group 6
Up to 6000 participants aged 18 years or older will receive ChAdOx1 nCoV-19 5x10(10) vp (qPCR)or MenACWY at day 0, then followed up at days 28, 90, 182 and 364
Group 7
80 participants aged 56-69 years will receive either single dose ChAdOx1 nCoV-19 5x10(10) virus particles (vp) (qPCR) or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY at day 0 and day 28, 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 ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or MenACWY at day 0 and day 28, 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
Volunteers will stay in the trial site for observation for 15 minutes (+15 minutes), in case of immediate adverse events.
In groups 1-3, 5 and in a subset of volunteers in groups 4 and 6 (n=1000, each), 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.
______
Previous interventions from 15/06/2020 to 24/06/2020:
Volunteers will initially be required to complete an online screening. This is an initial confirmation of eligibility. Volunteers will initially be invited for a screening visit. Prior to attending they will have received written information about the study and had time to consider it. At the screening visit, a doctor will explain about the study and answer any questions they may have. If the volunteer decides to take part, they will be asked to sign a consent form. The doctor will then check whether the volunteer is eligible to take part. This will involve taking a medical history, performing a physical examination, taking blood tests, urine tests, and measuring blood pressure and temperature.
The doctor will then write to the volunteer's own GP to enquire about their medical health. If all the inclusion criteria are met and none of the exclusion criteria are present then the volunteer is invited to return for vaccination. Due to the need for rapid delivery of this study, there will be minimal flexibility around appointment dates.
Before vaccination, volunteers will be asked about their recent health to ensure that they are still medically fit. They will have blood tests taken and participants will be randomised (Group 1: 3:1, Group 2: 5:1, Groups 3-6: 1:1) to receive either ChAdOx1 nCoV-19 or MenACWY.
Group 1
80 participants aged 56-<70 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) or MenACWY at day 0 and day 28, 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 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) or MenACWY at day 0 and day 28, 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 3
60 participants aged 5 to 12 years will receive ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) or MenACWY at day 0 and day 28, then followed up at days 3, 7, 28, 182 and 364
Group 4
Up to 3900 participants aged 18 years or older will receive ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) or MenACWY at day 0, then followed up at days 28, 90, 182 and 364
Group 5
100 participants aged 18-55 will receive ChAdOx1 nCoV-19 5x10(10) vp (Abs 260) or MenACWY at day 0, then followed up at days 3, 7, 14, 28, 56, 182 and 364
Group 6
Up to 6000 participants aged 18 years or older will receive ChAdOx1 nCoV-19 5x10(10) vp (qPCR)or MenACWY at day 0, then followed up at days 28, 90, 182 and 364
Volunteers will stay in the trial site for observation for 15 minutes (+15 minutes), in case of immediate adverse events.
In groups 1-3, 5 and in a subset of volunteers in groups 4 and 6 (n=1000, each), 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.
______
Previous interventions as of 04/06/2020:
Volunteers will initially be required to complete an online screening. This is an initial confirmation of eligibility. Volunteers will initially be invited for a screening visit. Prior to attending they will have received written information about the study and had time to consider it. At the screening visit, a doctor will explain about the study and answer any questions they may have. If the volunteer decides to take part, they will be asked to sign a consent form. The doctor will then check whether the volunteer is eligible to take part. This will involve taking a medical history, performing a physical examination, taking blood tests, urine tests, and measuring blood pressure and temperature.
The doctor will then write to the volunteer's own GP to enquire about their medical health. If all the inclusion criteria are met and none of the exclusion criteria are present then the volunteer is invited to return for vaccination. Due to the need for rapid delivery of this study, there will be minimal flexibility around appointment dates.
Before vaccination, volunteers will be asked about their recent health to ensure that they are still medically fit. They will have blood tests taken and participants will be randomised (Group 1: 3:1, Group 2: 5:1, Groups 3-5: 1:1) to receive either ChAdOx1 nCoV-19 or MenACWY.
Group 1
80 participants aged 56-<70 years will receive either single dose ChAdOx1 nCoV-19 5 x 10(10) virus particles (vp) or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, 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 2
120 participants aged 70 years or older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, 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 3
60 participants aged 5 to 12 years will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, then followed up at days 3, 7, 28, 182 and 364
Group 4
Up to 9900 participants aged 18 or older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, then followed up at days 28, 90, 182 and 364
Group 5
100 participants aged 18-55 older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, then followed up at days 3, 7, 14, 28, 56, 182 and 364
Volunteers will stay in the trial site for observation for 15 minutes (+15 minutes), in case of immediate adverse events.
In groups 1-3, 5 and in a subset of volunteers in group 4 (n=1000), 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.
_____
Previous interventions as of 22/05/2020:
Volunteers will initially be required to complete an online screening. This is an initial confirmation of eligibility. Volunteers will initially be invited for a screening visit. Prior to attending they will have received written information about the study and had time to consider it. At the screening visit, a doctor will explain about the study and answer any questions they may have. If the volunteer decides to take part, they will be asked to sign a consent form. The doctor will then check whether the volunteer is eligible to take part. This will involve taking a medical history, performing a physical examination, taking blood tests, urine tests, and measuring blood pressure and temperature.
The doctor will then write to the volunteer's own GP to enquire about their medical health. If all the inclusion criteria are met and none of the exclusion criteria are present then the volunteer is invited to return for vaccination. Due to the need for rapid delivery of this study, there will be minimal flexibility around appointment dates.
Before vaccination, volunteers will be asked about their recent health to ensure that they are still medically fit. They will have blood tests taken and participants will be randomised (Group 1: 3:1, Group 2: 5:1, Groups 3-5: 1:1) to receive either ChAdOx1 nCoV-19 or MenACWY.
Group 1
80 participants aged 56-<70 years will receive either single dose ChAdOx1 nCoV-19 5 x 10(10) virus particles (vp) or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, 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 2
120 participants aged 70 years or older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, 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 3
60 participants aged 5 to 12 years will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, then followed up at days 3, 7, 28, 182 and 364
Group 4
Up to 9900 participants aged 18 or older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, then followed up at days 28, 90, 182 and 364
Group 5
100 participants aged 18-55 older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, then followed up at days 3, 7, 14, 28, 56, 182 and 364
Participants will be observed for 60 minutes after vaccination (+/-30 minutes) and given an oral thermometer, tape measure and access to a diary with instructions for use. They will also receive an 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.
_____
Previous interventions:
Volunteers will initially be required to complete an online screening. This is an initial confirmation of eligibility. Volunteers will initially be invited for a screening visit. Prior to attending they will have received written information about the study and had time to consider it. At the screening visit, a doctor will explain about the study and answer any questions they may have. If the volunteer decides to take part, they will be asked to sign a consent form. The doctor will then check whether the volunteer is eligible to take part. This will involve taking a medical history, performing a physical examination, taking blood tests, urine tests, and measuring blood pressure and temperature.
The doctor will then write to the volunteer's own GP to enquire about their medical health. If all the inclusion criteria are met and none of the exclusion criteria are present then the volunteer is invited to return for vaccination. Due to the need for rapid delivery of this study, there will be minimal flexibility around appointment dates.
Before vaccination, volunteers will be asked about their recent health to ensure that they are still medically fit. They will have blood tests taken and participants will be randomised (1:1) to receive either ChAdOx1 nCoV-19 or MenACWY.
Group 1
80 participants aged 56-<70 years will receive either single dose ChAdOx1 nCoV-19 5 x 10(10) virus particles (vp) or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, then followed up at days 3, 7, 14, 28, 56, 182 and 364 (optional)
Group2
120 participants aged 70 years or older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, or two dose ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, then followed up at days 3, 7, 14, 28, 56, 182 and 364 (optional)
Group 3
60 participants aged 5 to 12 years will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0 and day 28, then followed up at days 3, 7, 28, 182 and 364 (optional)
Group 4
5000 participants aged 18 or older will receive ChAdOx1 nCoV-19 5 x 10(10) vp or MenACWY at day 0, then followed up at days 28, 90, 182 and 364 (optional)
Participants will be observed for 60 minutes after vaccination (+/-30 minutes) and given an oral thermometer, tape measure and access to a diary with instructions for use. They will also receive an 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
Phase
Phase II/III
Drug names
ChAdOx1-nCoV19, MenACWY
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 15/06/2020:
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 trial start date
02/03/2020
Overall trial end date
30/06/2021
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Current inclusion criteria as of 24/06/2020:
1. Adults aged 18 years or older (groups 4 and 6); aged 18-55 years (group 5)
2. Adults aged 56-69 years (groups 1 and 7)
3. Adults aged 70 years and older (groups 2 and 8)
4. Children aged 5-12 years inclusive (group 3)
5. Able and willing (in the Investigator’s opinion) to comply with all study requirements.
6. 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.
7. 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.
8. Agreement to refrain from blood donation during the course of the study.
9. Provide written informed consent.
10. Parent/guardian provides informed consent
_____
Previous inclusion criteria from 15/06/2020 to 24/06/2020:
1. Adults aged 18 years or older (groups 4 and 6); aged 18-55 years (group 5)
2. Adults aged 56 years or older (groups 1 and 2)
3. Children aged 5-12 years inclusive (group 3)
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
9. Parent/guardian provides informed consent
_____
Previous inclusion criteria as of 22/05/2020:
1. Adults aged 18 years or older (group 4); aged 18-55 years (group 5)
2. Adults aged 56 years or older (groups 1 and 2)
3. Children aged 5-12 years inclusive (group 3)
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
9. Parent/guardian provides informed consent
_____
Previous inclusion criteria:
1. Adults aged 18 or older (group 4)
2. Adults aged 56 or older (groups 1 and 2)
3. Children aged 5-12 inclusive (group 3)
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
9. Parent/guardian provides informed consent
Participant type
Healthy volunteer
Age group
Mixed
Gender
Both
Target number of participants
Up to 10,560 participants
Participant exclusion criteria
Current exclusion criteria as of 15/06/2020:
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
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)
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; 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
19. Seropositivity to SARS-CoV-2 before enrolment
Additional Exclusion criteria to Groups 4 and 6:
20. History of allergic disease or reactions likely to be exacerbated by Paracetamol
Additional Exclusion Criteria to Group 3:
21. Chronic medical conditions such as chronic lung disease, chronic liver disease, chronic renal failure, chronic heart disease, congenital genetic syndromes (e.g. Trisomy 21)
22. Fulfil any of the contraindications to vaccination as specified in The Green Book
_____
Previous exclusion criteria as of 22/05/2020:
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
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)
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; 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
19. Seropositivity to SARS-CoV-2 before enrolment
Additional Exclusion criteria to Group 4:
20. History of allergic disease or reactions likely to be exacerbated by Paracetamol
Additional Exclusion Criteria to Group 3:
21. Chronic medical conditions such as chronic lung disease, chronic liver disease, chronic renal failure, chronic heart disease, congenital genetic syndromes (e.g. Trisomy 21)
22. Fulfil any of the contraindications to vaccination as specified in The Green Book
_____
Previous exclusion criteria:
1. Current or planned participation in other clinical trial of an investigational medicinal product
2. Prior receipt of any vaccines (licensed or investigational) ≤30 days before enrolment
3. Planned receipt of any vaccine other than the study intervention within 30 days before and after each study vaccination
4. Prior receipt of an investigational or licensed vaccine likely to impact on interpretation of the trial data (e.g. Adenovirus vectored vaccines, any coronavirus vaccines)
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, including HIV infection; asplenia; recurrent severe infections and chronic use (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)
7. History of allergic disease or reactions likely to be exacerbated by any component of ChAdOx1 nCoV-19 or MenACWY
8. Any history of hereditary angioedema or idiopathic 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. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
15. Suspected or known injecting drug abuse in the 5 years preceding enrolment
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. History of laboratory-confirmed COVID-19
18. New onset of fever or a cough or shortness of breath since February 2020
19. Those who have been at high risk of exposure before enrolment, including but not limited to: close contacts of confirmed COVID-19 cases, anyone who had to self-isolate as a result of a symptomatic household member, frontline healthcare professionals working in A&E, ICU and other higher-risk areas and significant exposure associated with travel abroad to high incidence areas since January 2020
20. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban)
Additional exclusion criteria for Groups 1 and 2:
1. Chronic respiratory disease, including asthma
2. Severe and/or uncontrolled cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness (mild well-controlled comorbidities are allowed)
3. Seriously overweight (BMI ≥40 kg/m²)
4. History of auto-immune disease
Additional exclusion criteria for Group 3:
1. Chronic medical conditions such as chronic lung disease, chronic liver disease, chronic renal failure, chronic heart disease, congenital genetic syndromes (e.g. Trisomy 21)
2. Fulfil any of the contraindications to vaccination as specified in The Green Book
Recruitment start date
11/05/2020
Recruitment end date
30/06/2020
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Centre for Clinical Vaccinology & Tropical Medicine
University of Oxford
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
Trial participating centre
NIHR WTCRF
University Hospital Southampton NHS Foundation Trust
Southampton
SO16 6YD
United Kingdom
Trial participating centre
NIHR Imperial CRF
NIHR Imperial Clinical Research Facility Imperial College
Hammersmith Hospital, Imperial College NHS Trust
150 Du Cane Road
London
W12 0HS
United Kingdom
Trial participating centre
St Georges University Hospital NHS Foundation Trust
Blackshaw Road
Tooting
London
SW17 0TQ
United Kingdom
Trial participating centre
University Hospitals Bristol and Weston NHS Foundation Trust
Marlborough Street
Bristol
BS1 3NU
United Kingdom
Trial participating centre
North Bristol NHS Trust
Southmead Hospital
Southmead Road
Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom
Trial participating centre
University of Nottingham Health Service
Cripps Health Centre
University Park
Nottingham
NG7 2QW
United Kingdom
Trial participating centre
Sheffield Teaching Hospitals
Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2RX
United Kingdom
Trial participating centre
University Hospitals Birmingham NHS Foundation Trust (UHB)
Queen Elizabeth Hospital Birmingham
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
Trial participating centre
Wales (Public Health Wales)
Aneurin Bevan Local Health Board of Aneurin Bevan Local Health Board Headquarters,
St. Cadoc’s Hospital, Lodge Road, Caerleon,
Newport
NP18 3XQ
United Kingdom
Trial participating centre
Greater Glasgow and Clyde NHS Board
NHS Greater Glasgow and Clyde Corporate HQ
J B Russell House Gartnavel Royal Hospital Campus
1055 Great Western Road
Glasgow
G12 0XH
United Kingdom
Trial participating centre
Guy’s and St Thomas’ NHS Foundation Trust
Department of Infection
St Thomas Hospital
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Trial participating centre
Liverpool School of Tropical Medicine
Accelerator Research Clinic Clinical Sciences Accelerator
1 Daulby Street
Liverpool
L7 8XZ
United Kingdom
Trial participating centre
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom
Trial participating centre
UCLH
250 Euston Road
London
NW1 2PG
United Kingdom
Trial participating centre
NHS Lothian
Western General Hospital
Crewe Rd
Edinburgh
EH4 2XU
United Kingdom
Trial participating centre
NIHR Cambridge Clinical Research Facility
Cambridge Biomedical Campus
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Trial participating centre
Oxford University Hospital Foundation Trust
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom
Trial participating centre
Nottingham University Hospitals NHS Trust
C Floor
South Block
Queen's Medical Centre Campus
Derby Road
Nottingham
NG7 2UH
United Kingdom
Trial participating centre
Hull University Teaching Hospitals NHS Trust (HUTH)
Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Trial participating centre
Northwick Park Hospital
London North West University Healthcare Trust
Northwick Park Hospital
Watford Road
Harrow
HA1 3UJ
United Kingdom
Sponsor information
Organisation
University of Oxford
Sponsor details
Joint Research Office
1st floor
Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
United Kingdom
+44 (0)1865 616480
ctrg@admin.ox.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
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 statement:
The current data sharing plans for this study are unknown and will be available at a later date.
Intention to publish date
31/12/2021
Participant level data
To be made available at a later date
Basic results (scientific)
Publication list
Publication citations
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