A single-blind, randomised, phase II UK multi-centre study to determine reactogenicity and immunogenicity of heterologous prime/boost COVID-19 vaccine schedules
Closed to recruitment – in follow-up
Aim of the study
There are now a number of vaccines that have been approved to prevent COVID-19 in the UK. 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 they are primed with one type of vaccine, then boosted with another and to see how good the response is when the second dose is separated from the first dose by different periods of time.
The two vaccines in this study are AstraZeneca ChadOx1 nCoV-19 and Pfizer BioNTech BNT162b2. 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 combine different vaccines in this way, creates a more flexible immunisation programme, potentially allowing more people to be immunised more quickly. It will also give us useful information about extending the gap between prime and boost.
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 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 we 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 during the trial and have negative pregnancy tests on the days of vaccination
- You must agree not to donate blood during the trial
You cannot take part in this trial if you:
- Have already received one or more doses of the NHS COVID-19 vaccine
- Are already taking part in any trial looking to prevent COVID-19 through vaccines or medications
- Have any vaccine in the 30 days before or after this trial vaccine. 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 either of the two trial vaccine doses.
- Have previously received certain vaccines (such as other 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 methotrexate and steroid tablets
- Have ever had a severe allergic reaction (anaphylaxis)
- Have an allergy to any of the component of the COVID vaccines used in this study, including 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 BNT162b2 (Pfizer/BioNTech) vaccine. Known allergy to PEG is very rare.
- Are pregnant, breastfeeding or intend to become pregnant during the trial
- Have a current diagnosis of, or are having treatment for, cancer. Exceptions to this are certain skin cancers and pre-cancer of the cervix.
- 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, 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?
We are studying combinations of two different vaccines, and there will be 820 participants. As more 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 will be allocated, at random, (rather like a flip of a coin) to receive one dose of one approved vaccine and a second dose of either the same approved vaccine, or a dose of a different approved vaccine. Participants will also be allocated at random to the timing of receiving these doses – some will get a boost dose four weeks after the first dose (prime) and some will get a boost at twelve weeks.
- Between 5 and 9 routine blood tests will be taken over the course of a year 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 sample at each visit. If you were to test positive for the virus causing COVID-19 we may ask you to attend for an extra visit.
- Participants will need to complete an online diary for up to 28 days following each of the two vaccinations
- The trial will take one year to complete per participant (from the time the first dose of vaccine is given)
Results (if applicable)
‘Safety and Immunogenicity Report from the Com-COV Study – a Single-Blind Randomised Non-Inferiority Trial Comparing Heterologous And Homologous Prime-Boost Schedules with An Adenoviral Vectored and mRNA COVID-19 Vaccine’ – 25th June 2021 (link: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3874014)