Phase II Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy

This is a phase II, double-blind, exploratory, parallel-group, placebo-controlled clinical study in ambulant subjects with DMD resulting from a mutation that can be corrected by exon skipping induced by GSK2402968. The study aims to randomise 54 subjects. There will be 2 parallel cohorts. Each cohort will include subjects on GSK2402968 and matched placebo in a 2:1 ratio.

Inclusion criteria

• Ambulant subjects with Duchenne muscular dystrophy resulting from a mutation in the DMD gene, confirmed by a state-of-the-art DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping,
• Males, at least 5 years of age and with a life expectancy of at least 1 year
• Able to rise from floor in ≤7 seconds (without aids/orthoses),
• Able to complete the 6MWD test with a distance of at least 75m
• Receiving glucocorticoids for a minimum of 6 months immediately prior to screening, with no significant change in total daily dosage or dosing regimen for a minimum of 3 months immediately prior to screening and a reasonable expectation that total daily dosage and dosing regimen will not change significantly for the duration of the study
• QTc <450msec
• On adequate contraception
• Able to comply with and complete all protocol requirements

Exclusion criteria

• any additional missing exon for DMD
• Current of history of liver or renal disease or impairment
• Acute illness within 4 weeks of the first dose
• Use of prohibited meds within 6 months of fist dose
• Current participation in any other investigational clinical trial
• Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test at screening
• Symptomatic cardiomyopathy
• Children in Care