A phase II, double blind, exploratory, parallel-group, placebo-controlled clinical study to assess two dosing regimens of GSK2402968 for efficacy, safety, tolerability and pharmacokinetics in ambulant subjects with Duchenne muscular dystrophy

Phase 1

Conditions: Duchenne Muscular Dystrophy
MedDRA version: 14.0Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders

Registration Number: EUCTR2010-018412-32-BE

Lead Sponsor: GlaxoSmithKline Research and Development LTD

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Male

Target Recruitment: 54

Inclusion Criteria

1.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), SCAIP (Single Condition Amplification/Internal Primer) or H-RMCA (High-Resolution Melting Curve Analysis), and correctable by GSK2402968-induced DMD exon 51 skipping,
2.Aged at least 5 years,
3.Male,
4.Life expectancy of at least 1 year,
5.Able to rise from floor in =7 seconds (without aids/orthoses),
6.Able to complete the 6MWD test with a distance of at least 75m. In addition, results of 6MWD must be within 20% of each other at each pre-drug visit,
7.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,
8. 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, and machine read or manual overread,
9. Willing and able to comply with all protocol requirements and procedures,
10.Able to give informed assent and/or consent in writing signed by the subject and/or parent(s)/legal guardian (according to local regulations),
11.In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Are the trial subjects under 18? yes
Number of subjects for this age range: 54
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects meeting any of the following criteria must not be enrolled in the study:
1.Any additional missing exon for DMD that cannot be treated with GSK2402968,
2.Current or history of liver or renal disease or impairment,
3.Acute illness within 4 weeks of the first anticipated administration of study medication which may interfere with study assessments,
4.Use of anticoagulants, antithrombotics or antiplatelet agents, previous treatment with investigational drugs within 6 months of the first administration of study medication, and idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication,
5.Current or anticipated participation in any investigational clinical studies,
6.Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test at screening,
7.Symptomatic cardiomyopathy. If subject has a left ventricular ejection fraction <45% at Screening, the investigator should discuss inclusion of subject in the study with the medical monitor,
8.Children in Care. The definition of a Child in Care is a child who has been placed under the control or protection of an agency, organisation, institution or entity by the courts, the government or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: •To assess the safety and tolerability of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD.<br>•To assess the PK of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD.<br>•To assess long term efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD.<br>;Primary end point(s): Primary efficacy endpoint: <br><br>•Muscle function using 6 minute walking distance (6MWD) test.<br>;Timepoint(s) of evaluation of this end point: Every 12 weeks;Main Objective: •To assess the efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 24 weeks in ambulant subjects with DMD.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Timed function tests (times and grading):<br> -rise from floor<br> -10m walk/run<br> -4-stair climb<br>•Muscle strength (total score): knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors (as determined by handheld dynamometry)<br>•North Star Ambulatory Assessment<br>•Frequency of accidental falls (during 6MWD)<br>•Time to loss of ambulation<br>•Creatine kinase serum concentrations<br>•Pulmonary function (FEV1, FVC, MIP, MEP, PCF, PF)<br>•Dystrophin expression (muscle biopsies<br>;Timepoint(s) of evaluation of this end point: Various

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