Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

A Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy and Open-Label Extension

This study is a long-term study of ataluren in participants with nonsense mutation Duchenne muscular dystrophy.

This study is a randomized, double-blind, placebo-controlled, 72-week study, followed by a 72-week open-label period. The purpose is to characterize the long-term effects of ataluren-mediated dystrophin restoration on disease progression. Participants will be randomized in a 1:1 ratio to ataluren or placebo. Participants will receive blinded study drug three times daily (TID) at morning, midday, and evening for 72 weeks, after which all participants will receive open-label ataluren for an additional 72 weeks (144 weeks in total). Study assessments will be performed at clinic visits every 12 weeks during the double-blind period and every 24 weeks during the open-label period.

Inclusion Criteria:

• Male sex
• Age ≥5 years
• Phenotypic evidence of Duchenne Muscular Dystrophy
• Nonsense point mutation in the dystrophin gene
• Use of systemic corticosteroids (prednisone/prednisolone or deflazacort)for a minimum of 12 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen for a minimum of 3 months immediately prior to start of study treatment
• 6MWD ≥150 meters
• Ability to perform timed function tests within 30 seconds
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

• Any change in prophylaxis treatment for cardiomyopathy within 1 month prior to start of study treatment.
• Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy.
• Prior or ongoing therapy with ataluren.
• Known hypersensitivity to any of the ingredients or excipients of the study drug
• Exposure to another investigational drug within 6 months prior to start of study treatment, or ongoing participation in any interventional clinical trial.
• History of major surgical procedure within 12 weeks prior to start of study treatment, or expectation of major surgical procedure during the 72-week placebo-controlled treatment period.
• Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy.
• Uncontrolled clinical symptoms and signs of congestive heart failure
• Elevated serum creatinine or cystatin C at screening.