RAPID-PROTECTION
Research type
Research Study
Full title
RAPID-PROTECTION: An adaptive clinical trial of AZD7442 and SARS-CoV-2 vaccination in immunosuppressed patients highly vulnerable to infection with SARS-CoV-2 virus
IRAS ID
1004764
Contact name
Mark Tuthill
Contact email
Sponsor organisation
Cardiff University
Eudract number
2021-006703-15
ISRCTN Number
ISRCTN53507177
Research summary
Despite repeated vaccinations against COVID-19, some people with impaired immune systems caused by cancer and its treatment, inflammatory conditions, and those with organ transplants and other serious health conditions remain at very high risk of catching COVID-19 and becoming unwell.
AZD7442 (Evusheld) is a long-acting antibody treatment which has been shown in clinical trials to prevent COVID-19 infection for up to a year after a single injection. Unlike vaccinations, which take several doses given weeks apart to reach maximum efficacy, AZD7442 reaches effective levels within the body a few hours after an injection. AZD7442 has been approved for emergency use in the United States for the prevention of COVID-19 and is being considered for emergency use in UK to prevent COVID-19.
The RAPID-PROTECTION trial will determine the levels of immune protection that AZD7442 offers patients at the very highest risk of COVID-19 infection using laboratory based tests and whether or not this protection can be further enhanced by repeated vaccination against COVID-19. The participants will be enrolled in one of the following 4 cohorts: Haematological malignancies, Solid tumours, Renal and Hepatic disorders, and inflammatory disorders. All the participants in the study will receive AZD7442 and then 28 days later a COVID-19 vaccination that has been approved for use in the UK (currently vaccines by Moderna, Oxford/AstraZeneca, Pfizer/BioNTech, and Janssen). All the participants and their study teams will know which treatment and vaccines they have been offered in the study. They will be followed up for 1 year, and have blood tests before, during and after each study treatment. Unless the study team specifically advise otherwise, participants will not be able to receive any of the approved NHS COVID-19 vaccines (used within this study) for three months after receiving their booster vaccine on this study."Despite repeated vaccinations against COVID-19, some people with impaired immune systems caused by cancer and its treatment, inflammatory conditions, and those with organ transplants and other serious health conditions remain at very high risk of catching COVID-19 and becoming unwell. An antibody called AZD7442 (Evusheld) is a long-acting antibody treatment which has been shown in previous clinical trials to prevent COVID-19 infection for up to one year after a single dose was given to participants. The aim of the RAPID-PROTECTION trial was to determine the levels of immune protection that AZD7442 gave patients at the very highest risk of COVID-19 infection and whether this protection could be further enhanced by repeated vaccinations against COVID-19.The trial was funded by Astra Zeneca and was sponsored by Cardiff University. The trial team benefitted from the involvement of a patient and public member who was immunocompromised. Input was given into trial design and trial documentation and support for all aspects of the trial throughout. RAPID-PROTECTION was carried out in 5 NHS hospitals across England and Wales. Immunocompromised adults who had one of four pre-defined health conditions were eligible to enter the trial. All adults received the AZD7442 antibody and then were given one of two COVID-19 vaccines at 28 days. All the participants had blood tests taken before, during, and after each trial treatment to check the levels of AZD7442 and to examine their immune responses against COVID-19. Participants were followed up for 6 months.
The RAPID PROTECTION trial findings showed that AZD7442 can be safety administered with a COVID-19 vaccination to patients that are highly vulnerable to COVID-19 infection. We have described for the first time that AZD7442 leads to enhanced humoral and cellular immunity against COVID-19 and that this effect is further enhanced by vaccination, even against different strains of COVID-19 that are not targeted by the AZD7442 antibody itself. The mechanisms behind this effect are unclear and appear not be related to concurrent COVID-19 infection and are currently under investigation. This trial demonstrates that vaccination can lead to enhanced immunity against viral strains not neutralised by AZD7442 and should be considered as part of the development of future therapeutic antibodies like AZD7442."
REC name
London - Fulham Research Ethics Committee
REC reference
22/HRA/0359
Date of REC Opinion
25 Jul 2022
REC opinion
Further Information Favourable Opinion