A Bayesian Adaptive Trial in Duchenne Muscular Dystrophy

• Activity Number: 262 - The FDA Complex Innovative Trial Design Pilot Program: Learning from Case Examples and Simulations for the Public Good
• Type: Topic Contributed
• Date/Time: Tuesday, August 4, 2020 : 1:00 PM to 2:50 PM
• Sponsor: Biopharmaceutical Section
• Author(s): Stephen Lake* and Melanie Quintana and Scott Berry and Jennifer Panagoulias and Michael A. Panzara
• Companies: WAVE Life Sciences and Berry Consultants and Berry Consultants and Wave Life Sciences and Wave Life Sciences
• Keywords: Bayes; trial design ; adaptive; placebo augmentation; Duchenne Muscular Dystrophy; interim analysis

Abstract

A Bayesian adaptive trial design to evaluate a treatment for Duchenne Muscular Dystrophy will be presented. In the U.S., the primary endpoint was the change in dystrophin, while in other regulatory jurisdictions, the primary endpoint was the change in the North Star Ambulatory Assessment (NSAA). The trial design focused on achieving two goals: 1. To identify a treatment effect on dystrophin prior to study conclusion, 2. To maximize the probability of a definitive NSAA result. Interim analyses of dystrophin were planned to assess whether a significant treatment effect could be established before completion of study enrollment and follow-up. A Bayesian progression model for the change in NSAA which could dynamically augment the placebo arm of the trial with historical data was proposed. Prospective trial adaptation based on interim analysis of dystrophin and NSAA was planned, including the potential to drop a dose arm. The operating characteristics of the design were assessed via extensive simulation. This design was selected for the pilot FDA Complex and Innovative Trial Design Program. The experience of participation will be discussed.