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
- Conditions
- Duchenne Muscular DystrophyMedDRA version: 14.1Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disorders
- Registration Number
- EUCTR2010-018412-32-Outside-EU/EEA
- Lead Sponsor
- GlaxoSmithKline Research and Development LTD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- A
- Sex
- Male
- Target Recruitment
- 54
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
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>;Main Objective: •To assess the efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 24 weeks in ambulant subjects with DMD.;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
- 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