Conditions: Muscular Dystrophies
Keywords: 968 Duchenne Muscular Dystrophy GSK2402968 DMD Duchenne GSK
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 51
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine if GSK2402968 is effective in the treatment of ambulant boys with Duchenne muscular dystrophy resulting from a mutation thought to be corrected by exon 51 skipping. Two doses of GSK2402968 and placebo will be used in this study.

Detailed description:
Boys with Duchenne Muscular Dystrophy (DMD) suffer from a relentless, progressive and fatal disease due to lack of dystrophin, a critical muscle protein. There is currently no known cure for the disease. GSK2402968 is thought to correct several genetic mutations through skipping of exon 51 and therefore targets only those boys with these mutations.

A reasonable hypothesis is that increasing dystrophin will result in clinical improvement, and that the amount of dystrophin expressed will correlate with clinical improvement above a threshold level (e.g. around 30% of control). The initial limited efficacy data from completed and ongoing unblinded studies with GSK2402968 are encouraging as they have demonstrated de novo production of dystrophin and improved walking ability (primary efficacy endpoint) after 48 weeks of treatment which has been generally well tolerated.

This study is designed to explore the efficacy, safety and pharmacokinetics of two doses of GSK2402968 given over 24 weeks. The two doses to be assessed are 6mg/kg/week and 3mg/kg/week. Based on pharmacokinetic and pharmacodynamic modeling, it is predicted at steady-state that the 6 mg/kg/week dose will induce dystrophin expression greater than 30% of control. The 3 mg/kg/week dose was chosen as modeling predicts 3 mg/kg/week of GSK2402968 will produce dystrophin expression in the range of 18-22%. Potential variability between subjects could theoretically produce higher expression and lead to a dystrophin level correlated with clinical improvement.

Following the treatment period, the study has a 24 week post-treatment phase. The purpose of the post-treatment phase is to model the half-life of dystrophin, assess maintenance of response, and provide information about resolution of adverse event and laboratory abnormalities following cessation of treatment.

Arms:
arm 1: 3 mg/kg/week of investigational product arm 2: 6 mg/kg/week of investigational Product arm 3: Placebo arm 4: Placebo

Interventions: intervention 1: GSK2402968 3mg/kg/week intervention 2: GSK2402968 6 mg/kg/week intervention 3: Placebo to match GSK2402968 3 mg/kg/week intervention 4: Placebo to match GSK2402968 6 mg/kg/week
Intervention descriptions: intervention 1: Comparison of 2 doses of GSK2402968 intervention 2: Comparison of 2 doses of GSK2402968 intervention 3: Matched placebo intervention 4: Matched Placebo

Protocol document: