E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping |
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E.1.1.1 | Medical condition in easily understood language |
Duchenne muscular dystrophy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
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 |
The main objective of this study is to provide confirmatory evidence of efficacy of eteplirsen (AVI-4658) in Duchenne muscular dystrophy (DMD) patients that are amenable to skipping exon 51. |
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E.2.2 | Secondary objectives of the trial |
Additional objectives include evaluation of safety, biomarkers and the long-term effects of eteplirsen up to 96 weeks, followed by a safety extension (not to exceed 48 weeks). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male 7-16 years old 2. Diagnosed with DMD, genotypically confirmed 3. Stable dose of corticosteroids for at least 24 weeks 4. Have intact right and left alternative upper muscle groups 5. Mean 6MWT greater than 300m (primary analysis on 300 to 450 meters) 6. Stable pulmonary and cardiac function: predicted FVC equal to or greater than 50% and LVEF of greater than 50% |
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E.4 | Principal exclusion criteria |
1. Previous treatment with drisapersen or any other RNA antisense agent or any gene therapy within the last 6 months 2. Participation in any other DMD interventional clinical study within 12 weeks 3. Major surgery within 3 months 4. Presence of other clinically significant illness 5. Major change in the physical therapy regime within 3 months |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the change from Baseline to Week 96 in 6MWT. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from Baseline to Week 96 |
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E.5.2 | Secondary end point(s) |
1. Change from Baseline in percent of dystrophin-positive fibers by IHC (treated patients only) 2. Change from Baseline in dystrophin protein levels quantified by Western blot (treated patients only) 3. Ability to rise independently from the floor (without external support) as indicated by a North Star Ambulatory Assessment (NSAA) subscore of “2” (without modification) or “1” (Gower’s maneuver) 4. Loss of ambulation, defined as an inability to perform the 6MWT, or a result of “0” meters on the 6MWT 5. Change from Baseline in FVC % predicted 6. Change from Baseline in NSAA total score |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from Baseline to Week 96 |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
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.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |