Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

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

Detailed Description
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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. The total sample size of  250 subjects will include  160 subjects who meet the criteria for inclusion in the primary analysis population (age 7 to 16 years old, baseline six minute walk distance (6MWD) greater than or equal to (>=) 300 meters, supine to stand >= 5 seconds). The study will be conducted in the United States and other countries around the world.

Official Title
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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

Conditions
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Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Disease, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, X-Linked, Genetic Diseases, Inborn

Intervention / Treatment
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* Drug: Ataluren
* Drug: PLACEBO


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study describes the randomized, double-blind, placebo-controlled, 72-week study and its 72-week open-label extension
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ataluren<br>10, 20 milligrams per kilogram (mg/kg) | Drug: Ataluren<br>* 10, 20 mg/kg<br>* Other names: PTC124;|
| Placebo Comparator: Placebo<br>10, 20 mg/kg | Drug: PLACEBO<br>* 10, 20 mg/kg<br>* Other names: Matching Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks |  | 72 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 72 in 6MWD |  | Baseline, Week 72 | 
| Change from Baseline to Week 72 in Time to Run/Walk 10 Meters |  | Baseline, Week 72 | 
| Change from Baseline to Week 72 in Time to Climb 4 Stairs |  | Baseline, Week 72 | 
| Change from Baseline to Week 72 in Time to Descend 4 Stairs |  | Baseline, Week 72 | 
| Change from Baseline to Week 72 in North Start Ambulatory Assessment (NSAA) Total Score |  | Baseline, Week 72 | 
| Time to Loss of Ambulation Over 72 Weeks |  | 72 weeks | 
| Time to Loss of Stair-Climbing Over 72 Weeks |  | 72 Weeks | 
| Time to Loss of Stair-Descending Over 72 Weeks |  | 72 weeks | 
| Risk of Loss of NSAA Items Over 72 weeks |  | 72 weels | 
| Number of Treatment-Emergent Adverse Events Considered Related to Study Drug |  | 72 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PTC124, Ataluren, Duchenne Muscular Dystrophy, Dystrophinopathy, Nonsense Mutation, Premature Stop Codon, Becker Muscular Dystrophy, DMD/BMD