A Phase 2 Study to Evaluate the Efficacy and Safety of SRK-015 in Patients with Later-Onset Spinal Muscular Atrophy (TOPAZ): An Introduction

Clinical Trials
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Amy Place, PhD, MBA, MS, RD, CLT
1. Scholar Rock

SRK-015 is a fully human anti-proMyostatin monoclonal antibody that’s being developed and investigated for the treatment of later-onset SMA. This Phase 2 study involves approximately 25 study sites across United States, Canada and Europe. The study purpose is to evaluate the safety and efficacy of SRK-015 on motor function in SMA patients with Types 2 and 3, aged 2 through 21 years old, for 52 weeks. All patients received SRK-015 every 4 weeks via intravenous infusion. Patients in Cohorts 1 and 2 were directly assigned to a 20 mg/kg SRK-015 dose and patients in Cohort 3 were randomized 1:1 in a double-blind manner to either 2 mg/kg or 20 mg/kg SRK-015. Cohort 1 (N=20) enrolled ambulatory Type 3 patients, at least some of whom were not receiving an approved SMA up-regulator, as well as patients receiving an approved SMA treatment that was started after the patient turned 5 years old. Cohort 2 (N=15) enrolled Type 2 and non-ambulatory Type 3 patients already receiving an approved SMA up-regulator that was started after the patient turned 5 years old. Cohort 3 (N=20) enrolled Type 2 patients, who started on an approved SMA up-regulator before the patient turned 5 years old. The primary efficacy endpoint for Cohort 1 is the change from baseline in the Revised Hammersmith Scale. The primary efficacy endpoint for Cohorts 2 and 3 is change from baseline in Hammersmith Functional Motor Scale Expanded. Safety is being assessed throughout the trial by the Safety Surveillance Team. Blood samples for the measurement of SRK-015 concentrations, circulating latent myostatin concentrations, and anti-SRK-015 antibodies are being obtained. Demographic, baseline characteristics and preliminary PK/PD data will be presented.