Investigating a vaccine against COVID-19

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 September 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

https://www.covid19vaccinetrial.co.uk/home

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

EudraCT number

2020-001228-32

ClinicalTrials.gov number

NCT04400838

Protocol/serial number

CPMS 45551, IRAS 281904

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 25/08/2020:

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, 9-10: 1:1, a subgroup of Group 5 5:1) to receive either ChAdOx1 nCoV-19 or MenACWY. Group 11 is open-label and not randomised.

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.

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.

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 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
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 or 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 3, 7, 14, 28, 56, 182 and 364. Two dose subgroups will have additional visits at day 31, 35 and 42.

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
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
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.
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 and 11 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.

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, 7, 8 and 11 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.

_____

Previous interventions as of 04/08/2020:

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, 9-10: 1:1, a subgroup of Group 5 5:1) to receive either ChAdOx1 nCoV-19 or MenACWY. Group 11 is open-label and not randomised.

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 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 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. 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) or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) boost at day 0 and day 28, respectively, or two-dose MenACWY,at day 0 and day 28. The booster subgroup will be further followed up at days 28, 90, 182 and 365 after booster.

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 or 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, 56, 182 and 364. Two dose subgroups will have additional visits at day 31, 35 and 42.

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) or ChAdOx1 nCoV-19 5x10(10) vp (qPCR) or two-dose 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. 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 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 two dose ChAdOx1 nCoV-19 3.5-6.5 x10(10) vp (Abs 260, corrected for PS80) or 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 9
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 at day 0 and day 28, then followed up at days 28, 56, 118, 210 and 364.

Group 10
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 at day 0 and day 28, 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) at day 0 and day 28, then followed up at days 28, 56, 118, 210 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, 7, 8 and 11 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.

______

Previous interventions as of 30/07/2020:

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, 9-10: 1:1, a subgroup of Group 5 5:1) to receive either ChAdOx1 nCoV-19 or MenACWY. Group 11 is open-label and not randomised.

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 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 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. 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 at day 0 and day 28, respectively, or two-dose MenACWY,at day 0 and day 28. The booster subgroup will be further followed up at days 28, 90, 182 and 365 after booster.

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 or 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, 56, 182 and 364. Two dose subgroups will have additional visits at day 31, 35 and 42.

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) or two-dose 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. 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 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 two dose ChAdOx1 nCoV-19 3.5-6.5 x10(10) vp (Abs 260, corrected for PS80) 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 9
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 at day 0 and day 28, then followed up at days 28, 56, 118, 210 and 364.

Group 10
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 at day 0 and day 28, 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) at day 0 and day 28, then followed up at days 28, 56, 118, 210 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, 7, 8 and 11 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.

_____

Previous 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

Current 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 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

30/09/2021

Reason abandoned (if study stopped)

Participant inclusion criteria

Current inclusion criteria as of 30/07/2020:
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. 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

Participant type

Healthy volunteer

Age group

Mixed

Gender

Both

Target number of participants

Up to 12,330 participants

Participant exclusion criteria

Current exclusion criteria as of 25/08/2020:

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, with the exception of the seasonal influenza vaccination. Participants will be encouraged to receive this vaccination 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; 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
18.1 Seropositivity to SARS-CoV-2 before enrolment (except groups 5d, 9 and,10 and 11)

Additional Exclusion criteria to 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 to 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

Recruitment start date

11/05/2020

Recruitment end date

30/09/2020

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

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

http://www.ox.ac.uk/

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

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

31/03/2022

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

• 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_Previous inclusion and exclusion criteria.docx 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

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.