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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II, Double Blind, Exploratory, Parallel-group, Placebocontrolled Clinical Study to Assess Two Dosing Regimens of GSK2402968 for Efficacy, Safety, Tolerability and Pharmacokinetics in Ambulant Subjects With Duchenne Muscular Dystrophy

Conditions
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Muscular Dystrophies

Intervention / Treatment
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* Drug: GSK2402968
* Drug: matched placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 5 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous regimen; 6mg/kg once weekly<br>Once Weekly | Drug: GSK2402968<br>* Subcutaneous injection<br>* Other names: 968;Drug: matched placebo<br>* Subcutaneous injection<br>* Other names: Placebo;|
| Experimental: Intermittent regimen; 6mg/kg twice weekly<br>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 | Drug: GSK2402968<br>* Subcutaneous injection<br>* Other names: 968;Drug: matched placebo<br>* Subcutaneous injection<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 24 weeks in ambulant subjects with DMD |  | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects |  | one year | 
| To assess the PK of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD |  | 48 weeks | 
| To assess long term efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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968, muscular dystrophy, duchenne, DMD