Phase 2a Extension Study of Ataluren (PTC124) in Duchenne Muscular Dystrophy (DMD)

A Phase 2a Extension Study of PTC124 in Subjects With Nonsense-Mutation-Mediated Duchenne Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is a genetic disorder that develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of DMD in approximately 10-15% of boys with the disease. Ataluren is an orally-delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. This study is a Phase 2a extension trial that will evaluate the long-term safety of ataluren in boys with nonsense mutation DMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, strength, and other important clinical and laboratory measures.

This Phase 2a, multicenter, open-label safety and efficacy study will be performed at 3 sites in the United States. The study will enroll up to 38 participants with nonsense mutation Duchenne muscular dystrophy who participated in a previous Phase 2a study of ataluren (Protocol Number PTC124-GD-004-DMD [NCT00264888]). Participants will receive study drug 3 times per day (at breakfast, lunch, and dinner) for approximately 96 weeks (approximately 2 years). Study assessments will be performed at clinic visits during screening, every 6 weeks for the first 24 weeks, and then every 12 weeks until the end of the study. Additional safety laboratory testing, which may be performed at the investigational site or at an accredited local laboratory or clinic, is required every 3 weeks for the first 24 weeks and then every 6 weeks from Week 24 to Week 48. Participants will have a biceps muscle biopsy before ataluren treatment and again after 24 weeks of ataluren treatment to evaluate changes in muscle dystrophin expression. An evaluation of the effects of ataluren on corticosteroid pharmacokinetics will be performed. Associated with this ataluren clinical trial is a substudy that will use magnetic resonance evaluations to assess changes in the composition of muscles of the legs.

Inclusion Criteria:

• Completion of ataluren treatment in the previous Phase 2a study (Protocol PTC124-GD-004-DMD).
• Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age).
• Confirmed screening laboratory values within the central laboratory ranges.
• In participants who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 6-week follow up period.
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

• Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
• Treatment with warfarin within 1 month prior to start of study treatment.
• Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], and magnesium stearate).
• Exposure to another investigational drug within 2 months prior to start of study treatment.
• History of major surgical procedure within 1 month prior to start of study treatment.
• Ongoing immunosuppressive therapy (other than corticosteroids).
• Ongoing participation in any other clinical trial (except for sub-studies specifically approved by PTC Therapeutics).
• Clinically significant symptoms and signs of congestive heart failure (CHF) (American College of Cardiology/American Heart Association Stage C or Stage D).
• Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings, electrocardiogram findings, or laboratory abnormality that, in the Investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.