Clinical Trial: Ataluren for Nonsense Mutation Methylmalonic Acidemia

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Phase 2 Study of Ataluren (PTC124®) as an Oral Treatment for Nonsense Mutation Methylmalonic Acidemia

Brief Summary: Methylmalonic acidemia is a rare genetic disorder caused by mutations in the gene for mitochondrial enzyme methylmalonyl-CoA mutase (MCM) or in one of the genes for adenosylcobalamin (AdoCbl). Lack of these proteins causes toxic elevations of methylmalonic acid (MMacid) in blood, urine, and other tissues. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of the disease in approximately 5 to 20% of patients with mutations in the MCM gene, and approximately 20 to >50% of patients with mutations in one of the AdoCbl genes. Ataluren (PTC124) is an orally delivered, investigational drug that acts to overcome the effects of the premature stop codon, potentially enabling the production of functional MCM/AdoCbl. This study is a Phase 2a trial evaluating the safety and activity of ataluren in patients with methylmalonic acidemia due to a nonsense mutation. The main purpose of this study is to understand whether ataluren can safely decrease MMacid levels.

Detailed Summary: In this study, patients with methylmalonic acidemia due to a nonsense mutation will be administered an investigational drug called ataluren (PTC124). Evaluation procedures to determine if a patient qualifies for the study will be performed within 14 days prior to the start of drug administration. Eligible patients who elect to enroll in the study will then participate in 2 drug administration and follow-up periods. Within the first period, ataluren (PTC124) will be taken 3 times per day with meals for 28 days at doses of 5 mg/kg (morning), 5 mg/kg (midday) and 10 mg/kg (evening); there will then be an interval of approximately 21 days without ataluren (PTC124). Within the second period, ataluren (PTC124) will be taken 3 times per day with meals for 28 days at doses of 10 mg/kg (morning), 10 mg/kg (midday) and 20 mg/kg (evening); there will then be an interval of approximately 14 days without ataluren (PTC124). During the study, ataluren (PTC124) activity, safety, and pharmacokinetics will be evaluated, and MMacid levels in blood and urine will be measured periodically.
Sponsor: PTC Therapeutics

Current Primary Outcome: Change in plasma MMacid levels [ Time Frame: Baseline and 4 weeks in each cycle ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change in urinary MMacid levels [ Time Frame: Baseline and 4 weeks in each cycle ]
  • Effects of ataluren (PTC124) on additional markers of disease activity [ Time Frame: Baseline and 4 weeks in each cycle ]
  • Safety profile of ataluren (PTC124) as assessed by adverse events and laboratory data [ Time Frame: Baseline and 4 weeks in each cycle ]
  • Compliance with study drug administration [ Time Frame: Baseline and 4 weeks in each cycle ]
  • Ataluren (PTC124) plasma exposure [ Time Frame: Baseline and 4 weeks in each cycle ]


Original Secondary Outcome: Same as current

Information By: PTC Therapeutics

Dates:
Date Received: June 7, 2010
Date Started: June 2010
Date Completion: October 2012
Last Updated: October 31, 2011
Last Verified: October 2011