All Times EDT
Keywords: platform trial, shared control, estimand, Bayesian decision rules
Non-alcoholic steatohepatitis (NASH) is a complex disease that is associated with an increased risk of long-term mortality and cardiovascular disease for which there are currently no approved therapies and the failure rate of potential new treatments in Phase 2 and Phase 3 trials has been exceedingly high due to a heterogeneous patient patient population, endpoints that are difficult to measures and a lack of a strong relationship between early biomarkers and the endpoints that are required for regulatory approval. Until now, industry sponsors have performed standalone Phase 2b and Phase 3 clinical trials to demonstrate histologic efficacy often without demonstrating the necessary efficacy required for regulatory approval. With the challenges of clinical drug development during the COVID-19 pandemic the use of master protocols, especially platform trials have increased greatly in their use across a wide range of diseases in conditions. Given the challenges faced with clinical development of both monotherapy and combination therapy treatments in NASH, the design of platform trials would potentially offer benefits to many intervention owners with the possibility of the sharing of a common set of inclusion/exclusion criteria, Bayesian decision rules to evaluate the effectiveness of new treatments, common estimands, and a shared control arm to minimize the variability in standard of care response over time. We will discuss different alternatives for platform trials in NASH and key points to consider in the design of such trials in their implementation as single sponsor or multi-sponsor trials.