E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
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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] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
Evaluate the safety and tolerability of single ascending doses of WVE-210201 in patients with DMD. |
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E.2.2 | Secondary objectives of the trial |
Assess the pharmacokinetics (PK) of WVE-210201 in patients with DMD. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient and/or parent or legal guardian must have the ability and be willing to provide written informed consent prior to any study-related procedures. 2. Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase. 3. Documented mutation in the dystrophin gene associated with DMD that is amenable to exon 51 skipping. 4. Ambulatory or non-ambulatory male. 5. Age of ≥5 and ≤18 years at randomization tests, study restrictions, and all study procedures. 7. Stable pulmonary and cardiac function, documented within the past year, as measured by: a) Reproducible percent predicted forced vital capacity (FVC) ≥50% b) Left ventricular ejection fraction (LVEF) >55% in patients <10 years of age and >45% in patients ≥10 years of age, as measured (and documented) by echocardiogram. 8. Sexually mature males must be willing to use contraception for the duration of the study, if the patient is sexually active.
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E.4 | Principal exclusion criteria |
1. Clinically significant medical finding on the physical examination other than DMD that, in the judgment of the Investigator will make the patient unsuitable for participation in, and/or unable to complete the study procedures. 2. Other prior or ongoing medical conditions including: a) Acute illness within 28 days of Screening visit; b) Abnormal physical findings, other than those associated with musculoskeletal findings attributable to DMD. 3. Laboratory abnormality, that, in the Investigator's opinion, could adversely affect the safety of the patient, make it unlikely that the course of treatment or follow up would be completed, or impair the assessment of study results. These include, but are not limited to: a) Renal insufficiency; b) Impaired hepatic function (ALT (alanine aminotransferase) and AST (aspartate aminotransferase) elevations inconsistent with age and creatine kinase [CK] level, and elevated direct or indirect bilirubin); c) aPTT values above the upper limit of normal (ULN); d) Platelet count <lower limit of normal (LLN). 4. Severe mental retardation and/or behavioral problems that, in the opinion of the Investigator, could prohibit participation in this study. 5. Severe cardiomyopathy that, in the opinion of the Investigator, prohibits participation in this study. Cardiomyopathy that is managed by angiotensin-converting enzyme (ACE) inhibitors or beta blockers is acceptable provided the patient meets the LVEF inclusion criteria. 6. Need for mechanical or non-invasive ventilation OR anticipated need for mechanical or non-invasive ventilation within the next year, in the opinion of the Investigator. 7. Changes in nutritional or herbal supplements or concomitant medications within 1 month prior to Screening visit or plans to modify dose or regimen during the study. 8. Currently on anticoagulants or antithrombotics. 9 Received prior treatment with drisapersen. 10. Received treatment with eteplirsen or ataluren within the past 14 weeks. 11. Received any investigational drug within the past 3 months or 5 half-lives, whichever is longer.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the safety and tolerability of WVE-210201, as compared with placebo, as assessed by the number of patients with adverse events (AEs), severity of AEs, number of patients with serious AEs (SAEs), and the number of patients who withdraw due to AEs. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary safety endpoints will be assessed as incidence of events from baseline through end of study. |
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E.5.2 | Secondary end point(s) |
The secondary endpoint is the assessment of PK parameters of WVE-210201 following single dose administration. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 17 |
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 |
Belgium |
Czech Republic |
Denmark |
France |
Ireland |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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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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The end of the study is defined as the date on which the last patient completes the last visit (Day 85 ±3 days). |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |