A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy
Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which 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. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of dystrophinopathy 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. The main goal of this Phase 3 study is to evaluate the effect of ataluren on walking ability. The effect of ataluren on physical function, quality of life, and activities of daily living will be evaluated. This study will also provide additional information on the long-term safety of ataluren.
- drug : Placebo
- drug : Ataluren
Phase: Phase 3
Ages Eligible For Study:
- Ability to provide written informed consent (parental/guardian consent if applicable)/assent per local requirements. - Male sex. - Age ?7 and ?16 years. - Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (eg. proximal muscle weakness, waddling gait, and Gowers' maneuver) by 6 years of age, an elevated serum creatinine kinase level, and ongoing difficulty with walking. - Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization. - Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene. - Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a minimum of 6 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen (not related to body weight change) for a minimum of 3 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study. - Ability to walk ?150 meters unassisted during the screening 6-minute walk test. Patients need to be below the protocol-specified threshold for %-predicted 6MWD. - Results of the 2 Baseline 6MWD results must be determined as valid and results of the Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD. - Baseline 6MWD (mean of valid Day 1 and Day 2 values) must be no more than a 20% reduction from the valid Screening 6MWD. - Confirmed screening laboratory values within the central laboratory ranges (hepatic, renal, and serum electrolyte parameters) - Willingness to abstain from sexual intercourse or employ an approved method of contraception during the period of study drug administration and 6-week follow-up period. - Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.