A phase III study to investigate a vaccine against COVID-19
| ISRCTN | ISRCTN89951424 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN89951424 |
| Secondary identifying numbers | COV003 |
- Submission date
- 26/05/2020
- Registration date
- 11/06/2020
- Last edited
- 14/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Current plain English summary as of 25/11/2020:
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.
Since early 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. 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 in Brazil 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.
Who can participate?
Adults aged 18 and above
What does the study involve?
Participants are randomly allocated to receive two doses of the investigational vaccine or a well-established meningitis vaccine. Volunteers will be followed for 12 months after their final vaccine, and they will be tested for COVID-19 if they develop any symptoms which may represent COVID-19 disease. In addition, blood tests will be done during the study to look at how the volunteers' immune systems have reacted to the virus. At the end of the study, the researchers will look at how many people had COVID-19 disease in each group and this will help them to decide if the vaccine has worked.
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, the majority of participants in this study will not have had MenACWY vaccine previously, and therefore will gain the benefit of protection against group A, C, W and Y meningococcus. 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?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
May 2020 to March 2023
Who is funding the study?
University of Oxford (UK)
Who is the main contact?
Dr Peter O'Reilly
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.
Since early 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. 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 in Brazil 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.
Who can participate?
Adults aged 18 to 55
What does the study involve?
Participants are randomly allocated to receive the investigational vaccine or a well-established meningitis vaccine. Volunteers will be followed for 12 months, and they will be tested for COVID-19 if they develop any symptoms which may represent COVID-19 disease. In addition, blood tests will be done during the study to look at how the volunteers' immune systems have reacted to the virus. At the end of the study, the researchers will look at how many people had COVID-19 disease in each group and this will help them to decide if the vaccine has worked.
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, the majority of participants in this study will not have had MenACWY vaccine previously, and therefore will gain the benefit of protection against group A, C, W and Y meningococcus. 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?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
May 2020 to October 2021 (updated 04/08/2020, previously: July 2021)
Who is funding the study?
University of Oxford (UK)
Who is the main contact?
Dr Peter O'Reilly
covid19@ndm.ox.ac.uk
Contact information
Scientific
Oxford Vaccine Centre
Centre for Clinical Vaccinology & Tropical Medicine
University of Oxford
Churchill Hospital
Oxford
OX3 7LE
United Kingdom
| Phone | +44 (0)1865 611400 |
|---|---|
| covid19@ndm.ox.ac.uk |
Study information
| Study design | Single-blind randomised efficacy, safety and immunogenicity study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A phase III randomized controlled trial to determine safety, efficacy, and immunogenicity of the non-replicating ChAdOx1 nCoV-19 vaccine |
| Study acronym | COV003 |
| Study hypothesis | The candidate ChAdOx1 nCoV-19 vaccine is efficacious against PCR-confirmed COVID-19 disease. |
| Ethics approval(s) | 1. Approved 03/06/2020, The National Commission for Research Ethics (Comissão Nacional de Ética em Pesquisa (CONEP), SRTVN 701, Via W 5 Norte, lote D - Edifício PO 700, 3º andar, Asa Norte CEP, Brasilia, 70.719-040, Brazil; +55 61 3315-5877; conep@saude.gov.br), ref: 4068113 2. Approved 12/06/2020, Oxford Tropical Research Ethics Committee (OxTREC) (University of Oxford, Research Services, University Offices, Wellington Square, Oxford, OX1 2JD, UK; +44 (0) 1865 (2)82106; oxtrec@admin.ox.ac.uk), ref: 36-20 |
| Condition | COVID-19 (SARS-CoV-2 infection) |
| Intervention | Current interventions as of 25/11/2020: 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 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 and performing a physical examination if deemed necessary, taking blood tests for SARS-CoV-2 antibodies, urinary pregnancy test for women, and measuring blood pressure and temperature. Participants will be randomised (1:1 using block randomisation) to receive either ChAdOx1 nCoV-19 or MenACWY (licensed control vaccine). Participants will also be advised to take paracetamol for 24 hours after vaccination if there are no contraindications to doing so. Participants will be given two doses of ChAdOx1 nCoV-19 or MenACWY, 4-12 weeks apart. ChAdOx1 nCoV-19: 5 x 10(10) vp Men ACWY: 0.5 ml Two doses of ChAdOx1 nCoV-19 or MenACWY given intramuscularly. Paracetamol 1 g taken 6 hourly for the first 24 hours after receiving vaccine. Total follow up time 1 year for each study arm. All participants will be invited to follow-up visits at day 28, 90, 182 and 364 after their last vaccination. Participants will be asked to contact the study team if they develop symptoms suggestive of COVID-19 at any point during the trial. Symptomatic participants will be asked to present for a visit to test for SARS-CoV-2 PCR. Previous interventions: 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 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 and performing a physical examination if deemed necessary, taking blood tests for SARS-CoV-2 antibodies, urinary pregnancy test for women, and measuring blood pressure and temperature. Participants will be randomised (1:1 using block randomisation) to receive either ChAdOx1 nCoV-19 or MenACWY (licensed control vaccine). Participants will also be advised to take paracetamol for 24 hours after vaccination if there are no contraindications to doing so. ChAdOx1 nCoV-19: 5 x 10(10) vp Men ACWY: 0.5 ml One dose of ChAdOx1 nCoV-19 or MenACWY given intramuscularly. Single intervention only. Paracetamol 1 g taken 6 hourly for the first 24 hours after receiving vaccine. Total follow up time 1 year for each study arm. All participants will be invited to follow-up visits at day 28, 90, 182 and 364 and participants will be asked to contact the study team if they develop symptoms suggestive of COVID-19 at any point during the trial. Symptomatic participants will be asked to present for a visit to test for SARS-CoV-2 PCR. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | ChAdOx1 nCoV-19 vaccine, MenACWY vaccine |
| Primary outcome measure | Current primary outcome measure as of 25/11/2020: Virologically confirmed (PCV positive) symptomatic cases of COVID-19 over the course of 12 months Previous primary outcome measure: Virologically confirmed (PCR positive) symptomatic cases of COVID-19 over the course of 12 months |
| Secondary outcome measures | 1. Occurrence of solicited local and systemic reactogenicity signs and symptoms for 7 days following vaccination, recorded in an electronic diary (in a subset of 200 participants only) 2. Occurrence of serious adverse events reported by participant/documented in an electronic diary over the course of 12 months 3. Occurrence of disease enhancement episodes reported by participant/documented in hospital records over the course of 12 months 4. Hospitalization due to PCR-confirmed COVID-19 disease, reported by participants, over the course of 12 months 5. Severe PCR confirmed COVID-19 disease, parameters recorded from hospital records/participant interview, over the course of 12 months 6. Death associated with COVID-19 disease over the course of 12 months 7. Antibodies against SARS-CoV-2 non-spike protein (sero-efficacy rates) measured by ELISA over the course of 12 months 8. Antibodies against SARS-CoV-2 spike protein (sero-conversion rates) measured by ELISA at 28 days post vaccination 9. Virus neutralising antibody (NAb) assays against live and/or pseudotyped SARS-CoV-2 virus at 28 days post vaccination All participants will be invited to follow-up visits at day 28, 90, 182 and 364 following their last vaccination. Participants will be asked to contact the study team if they develop symptoms suggestive of COVID-19 at any point during the trial. Symptomatic participants will be asked to present for a visit to test for SARS-CoV-2 PCR. |
| Overall study start date | 01/05/2020 |
| Overall study end date | 31/03/2023 |
Eligibility
| Participant type(s) | Mixed |
|---|---|
| Age group | Mixed |
| Sex | Both |
| Target number of participants | 10300 (with a 1% margin) |
| Participant inclusion criteria | Current inclusion criteria as of 25/11/2020: 1. Adults aged 18 to 55 years of age 2. Adults aged 56-69 years old (after review of safety data by DSMB in this age group in the UK trial) 3. Adults aged 70 and above years old (after review of safety data by DSMB in this age group in the UK trial) 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/personal doctor and access all medical records when relevant to study procedures 4. 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 5. Agreement to refrain from blood donation during the course of the study 6. Provide written informed consent 7. Health professionals and/or adults at high risk of exposure to SARS-CoV-2 Previous inclusion criteria: 1. Adults aged 18 to 55 years of age. Upper age can be extended upon the availability of additional safety data in an older population 2. Able and willing (in the Investigator’s opinion) to comply with all study requirements 3. Willing to allow the investigators to discuss the volunteer’s medical history with their General Practitioner/personal doctor and access all medical records when relevant to study procedures 4. 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 5. Agreement to refrain from blood donation during the course of the study 6. Provide written informed consent |
| Participant exclusion criteria | 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 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 accidentally unblind participants to group allocation. Participation in COV003 can only be allowed if volunteers are kept blinded to their serology results from local/national serological surveys 3. Planned receipt of any vaccine (licensed or investigational), other than the study intervention, within 30 days before and after 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; asplenia; recurrent severe infections and chronic use (more than 14 days) 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 or paracetamol 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. Suspected or known current alcohol or drug dependency 15. 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) 16. History of laboratory-confirmed COVID-19 17. Seropositive for SARS-CoV-2 antibodies before enrolment 18. New onset of fever or a cough or shortness of breath or anosmia/ageusia since February 2020, unless seronegative for SARS-CoV-2 antibodies at screening 19. Continuous use of anticoagulants, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban) 20. 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 |
| Recruitment start date | 15/06/2020 |
| Recruitment end date | 31/12/2020 |
Locations
Countries of recruitment
- Brazil
Study participating centres
770 Vila Clementino
São Paulo
CEP 04038-001
Brazil
Rio de Janeiro
RJ, 22281-100
Brazil
Salvador
BA, 41253-190
Brazil
Natal
RN, 59025-050
Brazil
Santa Maria
RS, 97105-900
Brazil
Port Alegre
RS, 90035-903
Brazil
Sponsor information
University/education
Joint Research Office
1st floor
Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865 616480 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | http://www.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
University/education
No information available
Results and Publications
| Intention to publish date | 31/10/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Data from the study may also be used as part of a thesis for a PhD or MD. Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Interim results article | interim results | 09/01/2021 | 09/12/2020 | Yes | No |
| Results article | results | 06/03/2021 | 23/02/2021 | Yes | No |
| Results article | exploratory analysis of responses in males and females | 29/06/2022 | 04/07/2022 | Yes | No |
| Other publications | post-hoc exploratory analysis of the vaccine against the SARS-CoV-2 lineages circulating | 14/08/2024 | Yes | No |
Editorial Notes
14/08/2024: Publication reference added.
04/07/2022: Publication reference added.
19/01/2022: The following changes have been made:
1. The overall trial end date has been changed from 31/12/2021 to 31/03/2023 and the plain English summary has been updated to reflect this change.
2. The intention to publish date has been changed from 31/07/2022 to 31/10/2023.
23/02/2021: Publication reference added.
14/12/2020: Internal review.
09/12/2020: Publication reference added.
25/11/2020: The following changes were made to the trial record:
1. The overall end date was changed from 31/10/2021 to 31/12/2021.
2. The recruitment end date was changed from 31/08/2020 to 31/12/2020.
3. The interventions, primary outcome measures, inclusion criteria and plain English summary were updated.
4. The target number of participants was changed from 2000 to 10300 (with a 1% margin).
5. Instituto D'Or de Pesquisa e Ensino - I’Dor, Centro de Pesquisas Clinicas de Natal (CPCLIN), Universidade Federal de Santa Maria (UFSM) and Hospital das Clinicas de Porto Alegre Universidade Federal do Rio Grande do Sul (UFRGS) were added to the trial participating centres.
04/08/2020: The following changes were made to the trial record:
1. The overall end date was changed from 31/07/2021 to 31/10/2021.
2. The recruitment end date was changed from 31/07/2020 to 31/08/2020.
3. The plain English summary was updated to reflect these changes.
28/07/2020: The ethics approval was added.
12/06/2020: Internal review.
11/06/2020: Proof of trial's existence to be provided shortly after registration.
