Operational Development and Launch of an Adaptive Platform Trial in Amyotrophic Lateral Sclerosis: Processes and Learnings From the First Four Regimens of the <scp>HEALEY ALS</scp> Platform Trial
Brittney Harkey, Sofia DiStefano, Jaclyn Pagliaro, Lindsay Heyd, Marianne Chase, Courtney Igne, Hong Yu, Alexander V. Sherman, Derek D’Agostino, Eric Tustison, Genevive Changkuon, Meghan Hall, Gale Kittle, Mariah Connolly, Elisa Giacomelli, Erica Scirocco, James D. Berry, Suma Babu, Jeremy M. Shefner, Eric A. Macklin, Lori B. Chibnik, Annette De Mattos, Kristin Drake, Cornelia Kamp, Andrew McGarry, Margherita Torti, Catherine B. Small, Allison Bulat, Merit Cudkowicz, Sabrina Paganoni, for the HEALEY ALS Platform Trial Study Group
Abstract
INTRODUCTION/AIMS: Platform trials present several advantages over traditional interventional clinical trials. Here, we provide a detailed description of the operational framework of the HEALEY ALS Platform Trial. METHODS: Platform-level procedures for regulatory oversight, safety, and site management were developed prior to trial launch. Central vendors and a single Institutional Review Board (sIRB) were used. An Investigational New Drug (IND) application was submitted for the master protocol, and each regimen was added as an amendment. RESULTS: The HEALEY ALS Platform Trial was launched in 2020. Fifty-four geographically diverse sites from the Northeast ALS Consortium (NEALS), all highly experienced in ALS care and research, were selected. Three investigational products were selected to launch concurrently at the start of the trial as individual regimens. A fourth investigational product was selected and added to the trial after the initial launch. The Master Protocol and the first three regimens (Regimens A-C) were sIRB approved in 120 days. sIRB amendment for Regimen D was approved in 21 days. Enrollment for regimens A-C was completed in 15 months, whereas Regimen D was completed in 11 months from the start of enrollment. Results of all regimens were available within approximately 2 years from the initial trial launch. DISCUSSION: The HEALEY ALS Platform Trial capitalized on the benefits of the platform approach, including an adaptable operational infrastructure, concurrent enrollment into four distinct regimens, and an accelerated start-up time for a new regimen added after initial trial launch.