Design of REACH: Phase 3 Randomized, Double-Blind, Placebo-Controlled, 48-Week Study of the Efficacy and Safety of Losmapimod in FSHD
Alrabi Tawil1, Jay Han2, Leo Wang3, John Vissing4, Jeffrey Statland5, Jennifer Shoskes6, John Jiang6
1University of Rochester Medical Center, 2UCI Medical Center, 3University of Washington, 4University of Copenhagen, 5University of Kansas Medical Center, 6Fulcrum Therapeutics
Objective:
Evaluate the efficacy and safety of losmapimod for the treatment of FSHD.
Background:
FSHD is a chronic, variably progressive disease leading to accumulation of disability over decades. Nonclinical studies have shown that losmapimod (a small molecule p38 α/β MAPK inhibitor) reduces the aberrant expression of DUX4, the underlying cause of FSHD. Two Phase 2 clinical studies, a 48-week randomized controlled study (ReDUX4, FIS-002-2019) and a 52-week open-label study (OLS, FIS-001-2019) demonstrated evidence of benefit of treatment with losmapimod on muscle structure and function, as well as FSHD-relevant clinical endpoints that are recognized by patients and favorable safety and tolerability, supporting continued development. Fulcrum is initiating a Phase 3 double-blind, placebo-controlled trial to support the development of losmapimod in FSHD.
Design/Methods:
Approximately 230 people with FSHD, 210 with genetically confirmed FSHD1 and 20 with FSHD2, will be randomized 1:1 to receive losmapimod or placebo orally, twice daily for 48-weeks. The primary endpoint is reachable workspace quantification of total relative surface area (Q1-Q5) with 500 g wrist weight in the dominant arm, with secondary efficacy endpoints of quality of life in the neurological disorders upper extremity scale (Neuro-QoL UE), patient global impression of change (PGIC), and muscle fat infiltration (MFI) using whole-body musculoskeletal MRI (WB-MSK MRI). Exploratory assessments include muscle fat fraction, muscle strength by hand-held dynamometry, and patient reported outcomes (PRO) including patient global impression of severity (PGIS), a novel FSHD PRO, numeric pain rating scale (NPRS), 5-level EQ-5D (EQ-5D-5L) and healthcare utilization questionnaire.
Results:
The design of this Phase 3 study will be presented.
Conclusions:
The design of this Phase 3 study will be presented.