RAPID-PROTECTION

An adaptive clinical trial of AZD7442 and Vaxzevria (AZD1222/ChAdOx1 nCoV-19) in immunosuppressed patients that are highly vulnerable to infection with SARS-CoV-2 virus.

Despite repeated vaccinations against COVID-19, some people with weakened immune systems - caused by cancer, inflammatory conditions, as a result of organ transplants or other serious health conditions - remain at high risk of catching COVID-19 and becoming unwell.

AZD7442 is a combination of two long-acting antibodies that bind to the spike protein on the outside of the SARS-CoV2 virus and prevents the virus from entering human cells. It reaches effective levels in the body within a few hours after the injection, giving protection almost immediately.

The lack of immune response following SARS-COV-2 vaccination in certain vulnerable populations demonstrates the need of additional protection against infection. Several of the studies looking at AZD7442 protection were conducted whilst earlier COVID-19 variants were in circulation, for example in the phase III PROVENT trial. The PROVENT study has shown that treatment with a long acting antibody (AZD7442), provides immunity against SARS-COV-2 infection in participants that have not been vaccinated.

The virus has since continued to evolve with a number of different variants in circulation including Omicron. Although AZD7442 is effective against the current Omicron COVID-19 variants BA.4, BA.5, BA.1 and BA.1.1, the sensitivity of AZD7442 against these variants is reduced. It is also unknown how long the protection will last in immunocompromised people.

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. It is an adaptive platform which will allow increased recruitment in sub-groups of greatest uncertainty of effect.

The study will recruit an initial 350 participants with highly immunosuppressive conditions such as inflammatory disorders, solid tumours, haematological malignancies and renal/hepatic disorders including patients receiving transplants/dialysis. All the participants in the trial will receive AZD7442 and then 28 days later a COVID-19 vaccination with either the Moderna vaccine or Pfizer/BioNTech vaccine. All the participants will have blood tests before, during and after each trial treatments to check the levels of AZD7442 and to examine their immune responses against COVID-19 compared to age-matched healthy volunteers. Based on initial findings, cohorts of the immunosuppressive conditions may be expanded as part of the adaptive trial design.

We opened for recruitment on Friday 11 November 2022 at Oxford University Hospitals NHS Foundation Trust, The Royal Marsden Hospital (Sutton), and Northampton General Hospital. Our first participant was entered into the study today (15 November 2022) at Northampton General Hospital.