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 |
To explore safety and tolerability of eteplirsen in patients with advanced stage Duchenne muscular dystrophy (DMD) who are amenable to exon 51 skipping. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of eteplirsen on pulmonary function tests (PFTs) and other functional clinical measures.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male 7 - 21 years of age 2. Diagnosis of DMD with a mutation that is amenable to exon 51 skipping, confirmed by a genetic report 3. Stable dose of oral corticosteroids for at least 24 weeks or has not received corticosteroids for at least 24 weeks 4. Non-ambulatory, or incapable of walking ≥300 meters on the 6-Minute Walk Test (6MWT) 5. Score of ≤4 on the Brooke Score for Arms and Shoulders 6. Stable cardiac and pulmonary function 7. Use of contraceptives for sexually active males throughout the study |
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E.4 | Principal exclusion criteria |
1. Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks that may have an effect on muscle strength or function (e.g., growth hormone, anabolic steroids) 2. Previous treatment with SMT C1100/BMN 195 at any time 3. Previous treatment with drisapersen (PRO051) within the last 6 months 4. Participation in any other DMD interventional clinical study within 12 weeks 5. Major change in physiotherapy regimen within the past 3 months 6. Major surgery within 3 months 7. Presence of other clinically significant illness 8. Use of an aminoglycoside antibiotic within 12 weeks or the need for this antibiotic or statin during study 9. Forced vital capacity % predicted [FVC % predicted] <40%, or requiring daytime ventilation 10. Require antiarrhythmic and/or antidiuretic therapy for heart failure 11. Have a left ventricular ejection fraction (LVEF) of <40% 12. Prior or ongoing medical condition that could adversely affect the safety of the patient, make it unlikely that the course of treatment would be completed, or impair the assessment of study results |
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E.5 End points |
E.5.1 | Primary end point(s) |
The incidence of adverse events, clinical laboratory abnormalities, abnormalities in vital signs and physical examinations, and abnormalities on ECGs and ECHOs. |
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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) |
Change from Baseline to Week 96 in the following clinical measures of pulmonary function: 1. Maximum inspiratory pressure (MIP) % predicted 2. Maximum expiratory pressure (MEP) % predicted 3. MIP 4. MEP 5. FVC 6. FVC % predicted
Change from Baseline to Week 96 in the following functional clinical measures including: 1. Performance Upper Limb (PUL) 2. Brooke Score for Arms and Shoulders 3. 9-hole peg test 4. Ability Captured Through Interactive Video Evaluation (ACTIVE) 5. 10-Meter Walk/Run Test 6. Egen Klassifikation (EK) Scale 7. Biomarkers including micro-ribonucleic acid (miRNA) and matrix metalloproteinase 9 (MMP 9) 8. Anti-phosphorodiamidate morpholino oligomer (PMO) and anti-dystrophin antibodies
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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 | Yes |
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 | 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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |