A phase III study to investigate a vaccine against COVID-19

• Register: ISRCTN
• Last refreshed on: 5 August 2022
• Main ID: ISRCTN89951424
• Date of registration: 11/06/2020
• Prospective Registration: Yes
• Primary sponsor: University of Oxford
• Public title: A phase III study to investigate a vaccine against COVID-19
• Scientific title: A phase III randomized controlled trial to determine safety, efficacy, and immunogenicity of the non-replicating ChAdOx1 nCoV-19 vaccine
• Date of first enrolment: 15/06/2020
• Target sample size: 10300
• Recruitment status: Ongoing
• URL: https://www.isrctn.com/ISRCTN89951424
• Study type: Interventional
• Study design: Single-blind randomised efficacy, safety and immunogenicity study (Prevention)
• Phase: Phase III

Countries of recruitment

Brazil

Contacts

• Name: Peter O'Reilly

Key inclusion & exclusion criteria

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
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

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

COVID-19 (SARS-CoV-2 infection)
Infections and Infestations

Intervention(s)

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 co

Primary Outcome(s)

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(s)

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.

Secondary ID(s)

COV003

Nil known

Source(s) of Monetary Support

University of Oxford

Ethics review

Status:
Approval date:
Contact:

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; [phone]; [e-mail]), 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; [e-mail]),

Results

• Results available: Yes
• Date Completed: 31/03/2023