Clinical Trial: Safety and Efficacy Study of PTC124 in Duchenne Muscular Dystrophy

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2 Study of PTC124 as an Oral Treatment for Nonsense-Mutation-Mediated Duchenne Muscular Dystrophy

Brief Summary: In some patients with Duchenne muscular dystrophy (DMD), the disease is caused by a nonsense mutation (premature stop codon) in the gene that makes the dystrophin protein. PTC124 has been shown to partially restore dystrophin production in animals with DMD due to a nonsense mutation. The main purpose of this study is to understand whether PTC124 can safely increase functional dystrophin protein in the muscles of patients with DMD due to a nonsense mutation.

Detailed Summary: In this study, patients with DMD due to a nonsense mutation will be treated with a new investigational drug called PTC124. To determine if a patient qualifies for the study evaluation procedures will be performed within 21 days prior to the start of treatment; these procedures include: history, physical examination, blood and urine tests to assess organ function, electrocardiogram (ECG), muscle biopsy for evaluation of dystrophin protein, and DMD-specific tests of muscle function (for patients who are able to perform such tests). Eligible patients who elect to enroll in the study will then participate in a 28-day treatment period and a 28-day follow-up period (56 days total). The first 6 patients to be enrolled will take PTC124 treatment 3 times per day with meals for 28 days at doses of 4 mg/kg (breakfast), 4 mg/kg (lunch) and 8 mg/kg (dinner); these patients will then be observed during a 28-day follow-up period without treatment. Next, 18 additional patients will be enrolled to take PTC124 treatment 3 times per day with meals for 28 days at doses of 10 mg/kg (breakfast), 10 mg/kg (lunch), and 20 mg/kg (dinner); these patients will then be observed during a 28-day follow-up period without treatment. Subsequently, 6-12 additional patients will be enrolled to take PTC124 treatment 3 times per day with meals for 28 days at doses of 20 mg/kg (breakfast), 20 mg/kg (lunch), and 40 mg/kg (dinner); these patients will then be observed during a 28-day follow-up period without treatment. There will be a 2-night stay at the clinical research center at the beginning and at the end of the 28 days of PTC124 treatment. To assess efficacy, patients will have an end-of-treatment biopsy and will undergo DMD-specific tests of muscle function (for patients who are able to perform such tests). To assess safety and pharmacokinetics, safety assessments, blood and urine tests, and ECGs will be performed at prespecified timepoints during the 28-day treatment period and the 28-day follow-u
Sponsor: PTC Therapeutics

Current Primary Outcome: Dystrophin expression as assessed by immunofluorescence evaluation of tissue obtained by biopsy of the extensor digitorum brevis (EDB) muscle of the foot or tibialis anterior (TA) muscle of the leg

Original Primary Outcome: - Dystrophin expression as assessed by immunofluorescence evaluation of tissue obtained by biopsy of the extensor digitorum brevis (EDB) muscle of the foot

Current Secondary Outcome: Presence of dystrophin mRNA and dystrophin-related proteins on EDB or TA muscle biopsy, muscle function, compliance with treatment, safety and PTC124 pharmacokinetics

Original Secondary Outcome:

  • - Presence of dystrophin mRNA and dystrophin-related proteins on EDB muscle biopsy
  • - Muscle function
  • - Compliance with treatment
  • - Safety
  • - PTC124 pharmacokinetics


Information By: PTC Therapeutics

Dates:
Date Received: December 9, 2005
Date Started: December 2005
Date Completion:
Last Updated: January 9, 2009
Last Verified: January 2009