A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study Assessing PK, Safety, Tolerability in Non-ambulant DMD Subjects

Study Overview
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Brief Summary
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The purpose of this study is investigate the pharmacokinetics, safety and tolerability of single subcutaneous administration of GSK2402968 in non-ambulant boys with Duchenne muscular dystrophy

Official Title
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A Double-blind, Escalating Dose, Randomized, Placebo-controlled Study to Assess the Pharmacokinetics, Safety and Tolerability of Single Subcutaneous Injections of GSK2402968 in Non-ambulant Subjects With Duchenne Muscular Dystrophy

Conditions
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Muscular Dystrophies

Intervention / Treatment
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* Drug: 3 mg/kg GSK2402968
* Drug: 6 mg/kg GSK2402968
* Drug: 9 mg/kg GSK2402968
* Drug: 12 mg/kg GSK2402968
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Duchenne muscular dystrophy resulting from a mutation in the DMD gene, confirmed by a sponsor approved DNA diagnostic technique covering all DMD gene exons, including but not limited to MLPA (Multiplex Ligation-dependent Probe Amplification), CGH (Comparative Genomic Hybridisation), SCAIP (Single Condition Amplification/Internal Primer) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by treatment with GSK2402968. Age 9 years old or greater at Screening; Male; Non-ambulant (at least 1 year in a wheelchair) within the last 4 years; Life expectancy at least three years; Willingness and ability to comply with all protocol requirements and procedures; QTc <450msec (based on single or average QTc value of triplicate ECGs obtained over a brief recording period). Note: QTc may be either QTcB or QTcF, machine read or manual overread; Subjects must be willing to use adequate contraception (condoms or abstinence), from Screening until at least 5 months after the last dose of study drug; Informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations). Exclusion Criteria: Any additional mutation (such as an additional missing exon for DMD) that cannot be treated with GSK2402968; Current or history of liver or renal disease; Acute illness within 4 weeks of anticipated administration of study medication, which may interfere with study assessments; Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs, idebenone or other forms of Coenzyme Q10, within 6 months of the first administration of study medication; Start of glucocorticosteroids within 6 months or non-stable use of glucocorticosteroids within 3 months of the anticipated first administration of study medication; Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or human immunodeficiency virus (HIV) test at Screening; Symptomatic cardiomyopathy; Use of alcohol from Screening through to the 1 month Follow-up visit ; Any Child in Care.

Ages Eligible for Study
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Minimum Age: 9 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>3 mg/kg GSK2402968 / placebo | Drug: 3 mg/kg GSK2402968<br>* Weekly subcutaneous injection<br>Other: Placebo<br>* Weekly Placebo<br>|
| Experimental: Cohort 2<br>6 mg/kg GSK2402968 / placebo | Drug: 6 mg/kg GSK2402968<br>* Weekly subcutaneous injection<br>Other: Placebo<br>* Weekly Placebo<br>|
| Experimental: Cohort 3<br>9 mg/kg GSK2402968 / placebo | Drug: 9 mg/kg GSK2402968<br>* Weekly subcutaneous injection<br>Other: Placebo<br>* Weekly Placebo<br>|
| Experimental: Cohort 4<br>12 mg/kg GSK2402968 / placebo | Drug: 12 mg/kg GSK2402968<br>* Weekly subcutaneous injection<br>Other: Placebo<br>* Weekly Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Pharmacokinetic Variables:AUC, Cmax,t-max, CL/F |  | 35 days | 
| Incidence of Adverse Events |  | 35 days | 
| Incidence of Injection Site Reactions |  | 35 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DMD, Duchenne, Duchenne Muscular Dystrophy, 968