E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013801 |
E.1.2 | Term | Duchenne muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To assess the efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 24 weeks in ambulant subjects with DMD. |
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E.2.2 | Secondary objectives of the trial |
• To assess the safety and tolerability of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD.
• To assess the PK of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD.
• To assess long term efficacy of 2 different dosing regimens of subcutaneous GSK2402968 administered over 48 weeks in ambulant subjects with DMD.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title - Gait characterization by Accelerometry.
Date of version 1 – Sept 24, 2010
Objectives -
-test the applicability of Locometrix-2™ in measuring gait parameters with reproducibility and sensitivity in a pediatric population with DMD.
-compare the gait parameters between the 6MWD and a free walk test lasting 30s.
-correlate gait parameter values with clinical and functional data (e.g. knee extension force)
-compare gait parameters between DMD subjects and healthy control subjects
-test the sensitivity of Locometrix-2™ to detect gait changes along the disease in placebo-treated subjects
-assess drug efficacy with Locometrix-2™ in GSK2402968-treated subjects
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E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint:
• Muscle function using 6 minute walking distance (6MWD) test.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
•Timed function tests (times and grading):
•rise from floor
•10m walk/run
•4-stair climb
•Muscle strength (total score): knee flexors, knee extensors, elbow flexors, elbow extensors, shoulder abductors and hip flexors (as determined by handheld dynamometry)
•North Star Ambulatory Assessment
•Frequency of accidental falls (during 6MWD)
•Time to loss of ambulation
•Creatine kinase serum concentrations
•Pulmonary function (FEV1, FVC, MIP, MEP, PCF, PF)
•Dystrophin expression (muscle biopsies)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |