P.407 - Design of a phase 3 trial to evaluate the long-term efficacy and safety of ataluren in patients with nonsense mutation Duchenne muscular dystrophy

Abstract

Ataluren is conditionally approved by the European medicines agency to treat nonsense mutation Duchenne muscular dystrophy (nmDMD), with a specific obligation to conduct a long-term trial. This phase 3, randomized, double-blind, placebo-controlled trial with an open-label extension period is designed to evaluate the long-term efficacy and safety of ataluren in boys with nmDMD (Study 041). Patients eligible for participation will include those with phenotypic evidence of DMD, a nonsense mutation in the dystrophin gene, age ≥ 5 y, corticosteroid use for at least 12 months, 6-minute walk distance (6MWD) ≥ 150 m, and ability to perform timed function tests (TFTs) within 30 s. Patients will be randomized to receive ataluren 40 mg/kg/day (given orally in three doses: 10, 10 and 20 mg/kg) or placebo for 72 weeks. All patients will receive open-label ataluren in the 72 week extension. The primary endpoint will be slope of change from baseline to week 72 in 6MWD in a subset of patients aged ≥ 7 to ≤ 16 years with baseline 6MWD ≥ 300 m and time to stand from supine ≥ 5 s. Secondary and exploratory outcome measures will include TFTs, North Star Ambulatory Assessment, muscle strength (in patients <7 years old), upper limb function (in patients ≥7 years old), and health-related quality of life, as well as magnetic resonance imaging at a subset of sites. The open-label extension period will enable comparison of outcomes in patients who received ataluren from baseline to week 144 (early-start ataluren) with those in patients who received ataluren from week 72 to 144 (delayed-start ataluren). Safety parameters will be assessed throughout the double-blind and open-label periods. This study will enroll ~250 patients overall at sites in North America, Latin America, Europe, and Asia Pacific. Patient recruitment is planned to initiate in mid-2017 and close in mid-2018.