Lessons learned from a UK platform trial during the COVID-19 pandemic and beyond: The BEAT-Severe Asthma Trial

Background It is estimated that around 5% of people with asthma have severe asthma. Severe asthma typically presents with poor symptom control, impaired lung function and asthma exacerbations, despite regular inhaled steroids and additional controller medications. In the BEyond Allergic Th2-Severe Asthma clinical trials programme, we worked with severe asthma specialist centres in the United Kingdom to identify patients who experienced frequent asthma attacks (two or more per year), who were potentially eligible for stratified asthma treatments. Objectives There are currently two recognised subtypes of severe asthma which can be characterised by their level of eosinophils (a type of white blood cells). In the BEyond Allergic Th2-Severe Asthma clinical trial programme, we aimed to test whether a simple, once-daily oral antibiotic (doxycycline) can reduce asthma attacks in individuals with lower levels of eosinophils in peripheral blood (T2-Low arm: < 300 cells/µl). We also aimed to test whether a simple twice-daily oral drug (dexpramipexole) can reduce asthma attacks in individuals with high levels of eosinophils in peripheral blood (T2-High arm : ≥ 300 cells/µl). The trial was established using a master protocol and platform trial design with study protocols for the T2-High and T2-Low cohorts. Study outcomes The trial platform was successfully set up during the COVID-19 pandemic and opened across 13 sites in the United Kingdom for recruitment between August 2021 and September 2022, following a 12-month trial pause due to the pandemic. Several changes to the trial protocol were made to make the protocol easier to deliver due to pandemic restrictions. Due to capacity issues at National Health Service trusts in the United Kingdom following the pandemic, the trial was delayed in opening sites by approximately 4 months. Shortly after all sites were opened, a decision was made with the Trial Steering Committee and funders to close the dexpramipexole (T2-High) arm of the trial (October 2022), as the drug had moved on to definitive and confirmatory phase III trials. Recruitment into the doxycycline trial progressed slowly, largely in part due to challenges in finding people with asthma who had the required number of asthma attacks to be eligible, as attack rates in the United Kingdom fell during the pandemic. Furthermore, the trial was recruiting exclusively from severe asthma centres in the United Kingdom and did not have the funding required to change the recruitment model to include screening within primary care also. As a result of these factors, a decision was made by the sponsor of the trial to close the trial (April 2023), in line with National Institute for Health and Care Research post pandemic reset policy. Limitations and future work While no scientific conclusions can be drawn from this trial, following the pandemic a formal review of commercial clinical trials was commissioned by the government (Lord O’Shaughnessy review), with several recommendations to enhance clinical trial delivery in the United Kingdom. Many of the recommendations are applicable to non-commercial asthma trials. Furthermore, pivotal phase III trials of dexpramipexole are currently well underway. We would advocate the development of a Respiratory Clinical Trials Accelerator Platform for airways disease trials in the United Kingdom to support academic trials.