Ataluren for Nonsense Mutation Methylmalonic Acidemia

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Disease Information

Descriptive Information
Brief Title † Ataluren for Nonsense Mutation Methylmalonic Acidemia
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 Description 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.
Study Phase Phase 2
Study Type † Interventional
Study Design † Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary Outcome Measure † Change in plasma MMacid levels
Secondary Outcome Measure † Change in urinary MMacid levels
Condition † Amino Acid Metabolism, Inborn Errors
Intervention † DrugAtaluren (PTC124)
Study Arms / Comparison Groups Ataluren (PTC124)
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 24
Start Date † June 2010
Completion Date October 2012
Primary Completion Date July 2012
Eligibility Criteria † Major Inclusion Criteria: - Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if applicable) - Age ≥2 years - Phenotypic evidence of MMA based on the presence of characteristic clinical symptoms or signs and an elevated plasma MMacid level (>0.27 μmol/L) - Presence of a nonsense mutation in at least 1 allele of the mut, cblA, or cblB gene - Glomerular filtration rate ≥30 mL/min/1.73 m², serum aminotransferase values ≤2.5 x the upper limit of normal, serum bilirubin ≤1.5 x the upper limit of normal, plasma ACTH within normal limits - Willingness and ability to comply with scheduled visits, drug administration plan, study restrictions, and study procedures Major Exclusion Criteria: - Known hypersensitivity to any of the ingredients or excipients of the study drug - Any change in chronic treatment for methylmalonic acidemia within 2 months prior to start of screening laboratory assessments - Episode of metabolic decompensation within 1 month prior to start of Screening laboratory assessments - History of organ transplantation - Ongoing dialysis for renal dysfunction
Gender Both
Ages 2 Years - N/A
Accepts Healthy Volunteers No
Contacts ††
Location Countries † Belgium
Administrative Information
NCT ID † NCT01141075
Organization ID PTC124-GD-012-MMA
Secondary IDs ††
Responsible Party
Study Sponsor † PTC Therapeutics
Collaborators †† Genzyme, a Sanofi Company
Investigators † Study Director: Jay Barth, MD, PTC Therapeutics
Information Provided By
Verification Date October 2011
First Received Date † June 7, 2010
Last Updated Date October 31, 2011
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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