A single-blind, randomised, phase II UK multi-centre study to determine reactogenicity and immunogenicity of heterologous prime/boost COVID-19 vaccine schedules – Stage 2
Closed to recruitment – in follow-up
Aim of the study
There are now a number of vaccines in the UK that have been approved to prevent COVID-19, and others are expected to be approved in the near future. These use two-doses, a ‘prime’ first dose, followed by a ‘boost’ second dose some weeks later. The purpose of this trial is to see how well people’s immune systems respond when their second “boost” dose is a different type of vaccine to their first “prime” dose. We will also be looking at how common vaccine reactions, such as fever, are after such ‘mixed’ schedules. This is important, as being able to use different vaccines in this way creates a more flexible immunisation programme; potentially allowing more people to be immunised more quickly.
At present, the vaccines in this trial are:
- Oxford/AstraZeneca ChAdOx1 nCoV-19
- Pfizer/BioNTech BNT162b2
- COVID-19 Vaccine Moderna
- Novavax NVX-CoV2373
Inclusion and exclusion criteria
Adults that are aged 50 and over are able to take part. In order to be enrolled in the trial:
- You must have had your first dose of COVID-19 vaccine through the national immunisation programme between 29th January 2021-3rd March 2021.
- You must be able to provide documentation of this to the trial team, or allow the trial team to check this information via NHS systems
- You must be willing to tell the trial staff about your medical history, and you may be asked to allow the trial staff to check this with your General Practitioner (GP). Bear in mind that we would also notify your GP if you joined the trial (even if we did not need to check your medical history with them in advance).
- If you are able to become pregnant you must be willing to practice continuous effective contraception for three months after boost and have a negative pregnancy test on the day of any vaccination
- You must agree not to donate blood during the trial
You cannot take part in this trial if you:
- Have already received more than one dose of any COVID-19 vaccine
- Are already taking part in any trial looking to prevent COVID-19 through vaccines or medications
- Receive any other vaccine in the 30 days before or after COVID-19 vaccination in this study. The exceptions to this are the seasonal influenza vaccine and the pneumococcal vaccine (known as Pneumovax, which is routinely given to over 65-year olds). If you are offered these by your GP or your place of work, we ask that you have these at least 7 days before or after you receive the boost vaccine dose in this study.
- Have previously received certain vaccines (such as non-COVID adenovirus-based vaccines) that might impact on understanding your results. If you are not sure about this, please contact us to discuss.
- Have received a transfusion of any blood products, or immunoglobulins (antibodies) in the 3 months before having the trial vaccine
- Have immunosuppression or immunodeficiency – this includes being on medications that reduce the immune system such as steroid tablets
- Have ever had a severe allergic reaction (anaphylaxis)
- Have an allergy to any of the component of the COVID-19 vaccines used in this study. Specific allergies of concern are latex and polyethylene glycol/macrogol (PEG). PEGs are a group of known allergens commonly found in medicines, many household products and cosmetics, and are contained in the Pfizer and Moderna vaccines. Known allergy to PEG is very rare.
- Are pregnant, breastfeeding or intend to become pregnant within 3 months after vaccination
- Have received immunosuppressive chemotherapy or radiotherapy for treatment of cancer within the 6 months prior to enrolment.
- Have a bleeding disorder
- Continuously take medicines that reduce your blood clotting, such as coumarins and related anticoagulants (i.e. warfarin) or novel oral anticoagulants (i.e. apixaban, rivaroxaban, dabigatran and edoxaban)
- Have current alcohol or drug dependency
- Have severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, rheumatological disease, renal disease, endocrine disorder or neurological illness
- Have a history of confirmed COVID-19 by a validated test or have previously had a blood test that shows that you have had contact with the COVID-19 virus (antibody test)
What participating in the study involves?
In this study participants will receive a second dose of a COVID-19 vaccine that may differ from their first dose received through the national immunisation programme. We are aiming to recruit 1050 participants. As new SARS-CoV-2 vaccines become available, more vaccines may be included in the trial and so the total number of participants may increase.
- Participants must be 50 years and over, and have had one dose of a COVID-19 vaccine through the national immunisation programme approximately 8 to 12 weeks before being enrolled in the study. They cannot have received their boost dose already.
- Participants will be allocated, at random, to receive the same vaccine as their first dose “prime”, or one of two different COVID-19 vaccines.
- They will not know which vaccine they have received for their boost (i.e. they will be “blinded”)
- Between 5 and 7 routine blood tests will be taken over 10 months to look at the immune responses to the vaccine depending on the group you are in. You may also be asked for a nasal fluid and saliva sample at each visit. You might also be asked to attend for a repeat blood test if there were any safety concerns.
- Participants will need to complete an online diary for up to 28 days following the vaccine received in the trial
- Participants should expect their involvement in the trial to last approximately 10 months
- If you were to test positive for the virus causing COVID-19 we may ask you to attend for an extra visit.
The potential schedule of how the vaccines would be given is detailed below.
|Vaccine received in routine Immunisation Programme||Trial boost vaccine – one of the following options 8-12 weeks from first vaccine|
|(Approximately 525 participants in each group)||(Approximately 175 participants in each group)|