Recruitment into the RAPID-PROTECTION trial has been paused for this cohort of patients with immediate effect and the follow up period for trial participants has been decreased from 12 months down to only 6 months. The last follow up visit will now occur at Day 180.
The rationale for these changes is due to a FDA announcement that was released at the end of January advising that the use of Evusheld should be limited to when the combined frequency of non-susceptible SARS-CoV-2 variants nationally is less than or equal to 90%. The non-susceptible SARS-CoV-2 variants included the XBB, CH.1.1 and BQ.1 sub-lineages of the Omicron variant. At this time in the U.S fewer than 10% of circulating variants were susceptible to Evusheld so the FDA unauthorised the use of Evusheld until further notice.
The trial team met with AstraZeneca at the beginning of February to discuss the FDA announcement above and whether recruitment of patients within the UK to the RAPID-PROTECTION trial should continue. During this meeting, the data on the SARS-CoV-2 infection survey conducted within the UK published by the Office for National Statistics (ONS) was reviewed and it was concluded that the UK had not yet reached a threshold where ≥ 90% of the circulating variants were Evusheld resistant SARS-CoV-2 variants. Therefore, the decision was made to closely monitor the data published weekly by the ONS and once this threshold was breached, a further meeting should be conducted to discuss the status of the trial.
Unfortunately, the trial team met with AstraZeneca at the end of March to discuss the situation within the UK and the decision has now been made to pause recruitment within the RAPID-PROTECTION study since the percentage of circulating Evusheld resistant SARS-CoV-2 variants has now exceeded 90%.
The RAPID-PROTECTION study is trying to find a new way to protect patients who may be more vulnerable to developing severe COVID-19 due to current health conditions. Despite repeated vaccinations against COVID-19, some people with impaired immune systems caused by conditions such as cancer and its treatment, inflammatory conditions, and those with organ transplants and other serious health conditions, remain at high risk of catching COVID-19 and becoming unwell.
Evusheld is a long-acting antibody treatment which prevents COVID-19 infection. It reaches effective levels in the body within a few hours after the injection, giving protection almost immediately.
Several of the studies looking at Evusheld protection were conducted whilst earlier COVID-19 variants were in circulation, for example in the phase III PROVENT trial. In this trial, a single dose of 300mg of Evusheld reduced the risk of developing symptomatic COVID-19 by 77% when compared to a placebo, with protection lasting for at least 6 months. There were no cases of severe COVID-19 in those treated with Evusheld and the results show the side effects experienced were similar between the placebo and Evusheld groups.
The virus has since continued to evolve with a number of different variants in circulation including Omicron. Although we do know that Evusheld is effective against the current Omicron COVID-19 variants BA.4, BA.5, BA.1 and BA.1.1, the sensitivity of Evusheld against these variants is reduced. We also do not know how long the protection will last in immunocompromised people.
Emerging real world data, data from ongoing studies such as PROVENT and TACKLE, and scientific modelling suggests that increasing the dose of Evusheld from 300mg to 600mg should give 6 months of protection against COVID-19 as it continues to evolve. The higher dose of Evusheld (600mg) was found to be well tolerated and comparable to the lower dose of Evusheld (300mg).
Although we know that Evusheld does provide protection, we do not know how long for in people who are immunocompromised. This study will look at the levels of Evusheld over time in immunocompromised participants using blood tests. It will also test whether this protection can be further enhanced by giving a COVID-19 vaccine booster.