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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Muscular Dystrophies

Treatments: Drug: matched placebo; Drug: GSK2402968

Study type: Interventional

Funder types: Industry

Identifiers

NCT01153932

114117

Details and patient eligibility

About

The purpose of this study is to determine whether GSK2402968 given as a continuous dose and as an intermittent dose is effective and safe in the treatment of Duchenne muscular dystrophy.

Full description

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.

Enrollment: 53 patients

Sex: Male

Ages: 5+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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53 participants in 2 patient groups

Continuous regimen; 6mg/kg once weekly

Experimental group

Description:

Once Weekly

Treatment:

Drug: GSK2402968

Drug: matched placebo

Intermittent regimen; 6mg/kg twice weekly

Experimental group

Description:

Twice weekly on 1st, 3rd and 5th weeks, once weekly on 2nd, 4th and 6th weeks, and no active drug on 7th to 10th week of each 10 week cycle

Treatment:

Drug: GSK2402968

Drug: matched placebo