Conditions: Amino Acid Metabolism, Inborn Errors
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 11
Healthy volunteers: no

Brief summary:
Methylmalonic acidemia (MMA) 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 participants with mutations in the MCM gene, and approximately 20% to \>50% of participants with mutations in one of the AdoCbl genes. Ataluren 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 participants with MMA 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, participants with MMA due to a nonsense mutation will be administered an investigational drug called ataluren. Evaluation procedures to determine if a participant qualifies for the study will be performed within 14 days prior to the start of drug administration. Eligible participants who elect to enroll in the study will then participate in 2 drug administration and follow-up periods. Within the first period, ataluren will be taken 3 times per day with meals for 28 days at doses of 5 milligrams/kilograms (mg/kg) (morning), 5 mg/kg (midday), and 10 mg/kg (evening); there will then be an interval of approximately 21 days without ataluren. Within the second period, ataluren 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. During the study, ataluren activity, safety, and pharmacokinetics will be evaluated, and MMacid levels in blood and urine will be measured periodically.

Arms:
arm 1: Cycle 1: Ataluren treatment 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 21 up to 42 days without treatment.

Cycle 2: Ataluren treatment 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 14 days without treatment.

Interventions: intervention 1: Ataluren
Intervention descriptions: intervention 1: Ataluren will be provided as a vanilla-flavored powder to be mixed with water.

Protocol document: