Post-approval follow-up study for the COV001 and COV002 trials to determine the long-term safety and character of immune response to the Oxford-AstraZeneca coronavirus vaccine
| ISRCTN | ISRCTN16270186 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16270186 |
| EudraCT/CTIS number | 2021-003382-36 |
| IRAS number | 300456 |
| ClinicalTrials.gov number | NCT04324606 |
| Secondary identifying numbers | OVG2021/03, IRAS 300456, CPMS 50168 |
- Submission date
- 31/08/2021
- Registration date
- 01/09/2021
- Last edited
- 07/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English summary of protocol
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.
On the 29th December 2020 the UK regulator MHRA authorised the Oxford/AstraZeneca ChAdOx1 nCOV-19 vaccine for emergency use. The first participant received ChAdOx1 nCoV-19 on 23rd April 2020, so there is limited long-term data following human exposure to this new vaccine. Since 2012, several hundred patients have received different ChAdOx-based vaccines to prevent other diseases, including influenza, tuberculosis, prostate cancer and malaria, where to date, no serious adverse events were considered related to those vaccines. Under the “conditions of authorisation for emergency supply” in the UK and other territories, AstraZeneca agreed to meet the demands of a pharmacovigilance risk management plan to provide ongoing monitoring of individuals who have received the vaccine.
This safety and immunogenicity extension study aims partly to fulfil those obligations, while also gathering data to permit investigation into the character and persistence of the immune responses that have been stimulated. As such, this is an observational study, where the researchers do not propose to administer additional medicines. The risk to participants is limited to those resulting from simple blood tests at the two study visits. The findings that result from COV009 will be valuable to vaccine developers and policymakers to inform decisions on future vaccine scheduling and design.
Who can participate?
Participants previously enrolled in the UK Phase I/II (COV001) and Phase II/III (COV002) trials
What does the study involve?
Participants will be assessed at two study visits at 6 and 12 months. Each study visit will consist of a blood draw and collection of information on new adverse events since enrolment.
What are the possible benefits and risks of participating in the study?
The participants will have the opportunity to help clinicians better understand the long-term safety of the Oxford/AstraZeneca vaccine. The risks are limited to localised bruising and discomfort can occur at the site of blood sampling. Infrequently fainting may occur. The majority of the blood draws are small volumes.
Where is the study run from?
University of Oxford (UK)
When is the study starting and how long is it expected to run for?
August 2021 to December 2024
Who is funding the study?
AstraZeneca (UK)
Who is the main contact?
Nelly Owino, nelly.owino@paediatrics.ox.ac.uk
Contact information
Scientific
Oxford Vaccine Group
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom
| Phone | +44 (0)1865611400 |
|---|---|
| andrew.pollard@paediatrics.ox.ac.uk |
Public
Project Manager
Oxford Vaccine Group
Department of Paediatrics
University of Oxford
Centre for Clinical Vaccinology and Tropical Medicine
Churchill Drive
Oxford
OX3 7LE
United Kingdom
| Phone | +44 (0)1865611400 |
|---|---|
| nelly.owino@paediatrics.ox.ac.uk |
Study information
| Study design | Multi-centre prospective safety study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Prevention |
| Participant information sheet | ISRCTN16270186 COV009 PIS V4.0 18 Jul 2022.clean.pdf |
| Scientific title | Safety and immunogenicity extension study for ChAdOx1 nCoV-19 |
| Study acronym | COV009 |
| Study objectives | This study aims to: 1. Document the long-term safety profile of the ChAdOx1 nCoV-19 vaccine 2. Evaluate the character and durability of immune responses that are stimulated by the ChAdOx1 nCoV-19 vaccine |
| Ethics approval(s) | Approved 20/08/2021, South Central - Berkshire Research Ethics Committee (Bristol REC Centre, Temple Quay House, 2 The Square, Temple Quay, Bristol, BS1 6PN, UK; +44 (0)207 104 8372; berkshire.rec@hra.nhs.uk), REC ref: 21/SC/0261 |
| Health condition(s) or problem(s) studied | COVID-19 (SARS-CoV-2 infection) |
| Intervention | The study aims to enrol participants in parallel with the final visit of their parent trial (COV001/002), provided they have consented to be contacted for future research. At consent, participants will have sufficient opportunity to read and understand the contents of the patient information sheet prior to being invited to give informed written consent, with further opportunities to ask questions and seek clarification at the consent and enrolment visit. Participants will be consented to allow the central study team to access their NHS SARS-CoV-2 nucleic acid amplification test (NAAT) results including viral sequencing where it is available from NHS digital and local sequencing labs, using the participants NHS number or other personal identifiers in the event of a diagnosis of COVID-19 during the study period. Consent will also be sought to access all participant’s COVID-19 vaccination records through NHS digital or by accessing medical records. The following data will be collected for any participant that has completed the final study visit for the parent trial on a different day to enrolment in COV009. Any new: 1. COVID-19 diagnoses 2. Serious adverse events (SAEs) 3. Adverse events of special interest (AESI) 4. Administration of any vaccines 5. Participation in other clinical trials Participants will be assessed at two study visits after consent and enrolment: 1. At 6 months (study visit 1 – SV1) 2. At 12 months (study visit 2 – SV2) Each study visit will consist of a blood draw for immunology and questions to capture details of any of the following new events since enrolment: 1. COVID-19 diagnoses 2. Serious adverse events (SAEs) – the participant may also be asked about any new medical diagnoses or medically attended adverse events to ensure any SAEs are not missed 3. Adverse events of special interest (AESI) 4. Administration of any vaccines (any vaccine including but not limited to COVID vaccines are permissible but must be recorded in the eCRF) 5. Participation in other clinical trials In the event that a participant is unable to attend an in-person clinic visit, telephone safety assessments may be conducted instead. Participants will be able to contact the study team outside of study visits 1 and 2 to report any new relevant medical event as stated in the patient information sheet Following enrolment, some participants (Oxford and Southampton sites only) will be allocated sequentially at enrolment to the exploratory immunology subgroup. For most participants up to 10 ml of blood will be taken at each of the two visits, totalling 20 ml for the study. For those participants allocated to the ‘exploratory immunology’ subgroup, a larger volume of blood, up to 50 ml at each visit, will be taken. Each participant may exercise his or her right to withdraw from the study at any time. In addition, the investigator may terminate a participant’s involvement in the study, at any time, if the investigator considers it necessary. |
| Intervention type | Biological/Vaccine |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Not provided at time of registration |
| Primary outcome measure | Long-term safety of the ChAdOx1 nCoV-19 vaccine measured from the registry of serious adverse events (SAEs) and adverse events of special interest (AESIs) at visit 1 (6 months, +/- 28 days) and visit 2 (12 months, +/- 28 days) and may also be reported by the participant at other times during the study |
| Secondary outcome measures | Character and durability of the immune response to vaccination measured by the immune responses (for a subset of participants, in exploratory immunology group), anti-SARS-CoV-2 spike protein immunoglobulins, and neutralising antibodies against SARS-CoV-2 at visit 1 (6 months +/- 28 days) and visit 2 (12 months +/-28 days) |
| Overall study start date | 20/08/2021 |
| Completion date | 31/12/2024 |
Eligibility
| Participant type(s) | Other |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Up to 12,000 participants from the COV001 and COV002 trials |
| Total final enrolment | 1077 |
| Key inclusion criteria | 1. Participated in the COV001 - Phase I/II or COV002 - Phase II/III trials 2. Able and willing to provide written, informed consent to participate in the study 3. Able and willing (in the investigator’s opinion), to comply with all study requirements 4. Consent to general practitioner or responsible physician being notified of participation in the study 5. Consent to allow investigators to discuss their medical information with their general practitioner (GP) or responsible physician, and to access any medical records where relevant to the study 6. Consent to access NHS SARS-CoV-2 NAAT results, including viral sequencing, results from NHS Digital and local sequencing labs, as well as COVID-19 vaccination records if available |
| Key exclusion criteria | 1. Participants who have enrolled on a clinical trial of an investigational medicinal product (CTIMP) for a novel COVID-19 vaccine will be excluded. Examples would include the COV-Variant or ComCOV trials 2. Participants who fail to enrol onto COV009 within 26 weeks of their last study visit on the parent study will be excluded. If consent is not obtained within 26 days from the last visit on the parent trial, the participant will become ineligible for COV009 |
| Date of first enrolment | 01/09/2021 |
| Date of final enrolment | 31/08/2022 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
CCVTM
Oxford
OX3 7LE
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
South Wharf Road
London
W2 1BL
United Kingdom
Mindelsohn Way
Edgbaston
BIrmingham
B15 2GW
United Kingdom
Blackshaw Road
Tooting
London
SW17 0QT
United Kingdom
Sheffield
S5 7AU
United Kingdom
Caerleon
Newport Gwent
NP18 3XQ
United Kingdom
Harrow
HA1 3UJ
United Kingdom
Bristol
BS10 5NB
United Kingdom
Bristol
BS1 3NU
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Glasgow
G12 0XH
United Kingdom
Newcastle Upon Tyne
NW12PG
United Kingdom
Hull
HU3 2JZ
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Westminster Bridge Road
London
SE1 7EH
United Kingdom
Cranmer Terrace
London
SW17 0RE
United Kingdom
Liverpool
L3 5QA
United Kingdom
Sponsor information
University/education
Clinical Trials and Research Governance (CTRG)
University of Oxford Joint Research Office
1st Floor, Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 &LQ
United Kingdom
| Phone | +44 (0)1865289885 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | https://researchsupport.admin.ox.ac.uk/ctrg |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Industry
Government organisation / For-profit companies (industry)
- Alternative name(s)
- AstraZeneca PLC, Pearl Therapeutics
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 30/04/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available. Summary data only will be published. No identifiable personal data will be used. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.1 | 24/08/2021 | 31/08/2021 | No | No |
| Protocol file | version 3.0 | 28/10/2021 | 29/11/2021 | No | No |
| Participant information sheet | version 4.0 | 18/07/2022 | 19/08/2022 | No | Yes |
| Protocol file | version 4.0 | 18/07/2022 | 19/08/2022 | No | No |
| HRA research summary | 26/07/2023 | No | No | ||
| Protocol file | version 4.1 | 18/07/2024 | 07/08/2024 | No | No |
Additional files
Editorial Notes
07/08/2024: The following changes were made:
1. Uploaded protocol v4.1 (not peer-reviewed) as an additional file.
2. The overall study end date was changed from 31/08/2024 to 31/12/2024.
3. The intention to publish date was changed from 31/12/2024 to 30/04/2025
4. The total final enrolment number was added.
5. The individual participant data (IPD) sharing plan was added.
6. The ClinicalTrials.gov number was added.
07/11/2023: The contact confirmed the record is up to date.
19/08/2022: The following changes have been made:
1. Protocol v4.0 has been uploaded.
2. The participant information sheet v4.0 has been uploaded.
2. 09/06/2022: Contact details updated.
10/01/2022: The Scientific contact has been removed from the plain English summary.
29/11/2021: The following changes have been made:
1. The recruitment end date has been changed from 31/12/2022 to 31/08/2022.
2. The overall trial end date has been changed from 31/12/2023 to 31/08/2024 and the plain English summary updated accordingly.
3. Protocol v3.0 has been uploaded.
01/10/2021: The CPMS number was added to the protocol/serial no. field.
31/08/2021: Trial's existence confirmed by South Central - Berkshire Research Ethics Committee.
