Trial design for the Phase 2 FORGE study evaluating apitegromab in adults with facioscapulohumeral muscular dystrophy

Topic:

Clinical Trials

Poster Number: 308 T

Author(s):

John Staropoli, MD, PhD, Scholar Rock, Jeffrey Statland, MD, University of Kansas Medical Center, Kansas City, Kansas, USA, Nicholas Johnson, MD, Virginia Commonwealth University, Richmond, Virginia, USA , John Vissing, MD, Neurology at the University of Copenhagen, Ryan Frieler, PhD, Scholar Rock, Guochen Song, DrPH, Scholar Rock, Jing Marantz, MD, PhD, Scholar Rock, Inc., Tina Duong, PT, PhD, Stanford University School of Medicine, Leslie Nelson, MPT, PhD, University of Texas Southwestern Medical Center

FSHD is a primary myopathy characterized by progressive and asymmetric weakness of the facial, shoulder, and lower limb muscles. Apitegromab is an investigational, monoclonal antibody that selectively inhibits activation of myostatin, a negative regulator of muscle growth, thus increasing muscle mass and motor function. In clinical studies for SMA (Phase 2 TOPAZ, NCT03921528; Phase 3 SAPPHIRE, NCT05156320), apitegromab was well-tolerated and reliably improved motor function across a broad range of patients who were also receiving SMN-targeted treatment. Nonclinical studies in a FLExD murine model of FSHD showed that the murine analog of apitegromab (muSRK-015) significantly increased skeletal muscle mass, muscle force, and endurance.

FORGE is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study that will assess the efficacy, pharmacokinetics, pharmacodynamics, safety, and tolerability of apitegromab in patients with FSHD.

Approximately 60 ambulatory adult patients (aged 18-60y) with genetically confirmed FSHD (FSHD1/FSHD2), a clinical severity score of 1.5-3.0 (Ricci score), and baseline 10MWRT time ≤5s, will be recruited to participate in the FORGE study. Individuals with any medical condition, clinically significant laboratory result, or ECG value that may compromise safety, interfere with study compliance, or confound the interpretation of the results, are ineligible for the study. Patients eligible for enrollment will be randomized to receive apitegromab 10 mg/kg monotherapy or placebo by intravenous infusion Q4W. FORGE will include a screening period of up to 4 weeks, a 52-week treatment period (13 doses), and a 20-week safety follow-up period for patients not entering the open-label extension study. The primary endpoint will be percent change from baseline in total lean muscle volume by MRI at week 52.

Building on the foundational evidence from previous work, FORGE aims to investigate apitegromab, a muscle-targeted treatment, in the adult FSHD patient population and is expected to be conducted across 20 sites in North America and Europe.