E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Sense Mutation Duchenne Muscular Dystrophy (nmDMD) |
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E.1.1.1 | Medical condition in easily understood language |
Non-Sense Mutation Duchenne Muscular Dystrophy (nmDMD) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
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 change in levels of dystrophin in ambulatory nmDMD subjects after treatment with ataluren for 40 weeks using quantitative assay, such as electrochemiluminescence (ECL) |
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E.2.2 | Secondary objectives of the trial |
To assess dystrophin levels/intensity and protein localization by immunohistochemistry after 40 weeks of ataluren treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male aged 2 to less than 8 years old. • Phenotypic evidence of duchenne muscular dystrophy (DMD) based on the onset of characteristic clinical symptoms or signs (for example, proximal muscle weakness, waddling gait, and Gowers’ maneuver) and an elevated serum creatine kinase (CK). • Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing. • Willing to undergo muscle biopsy. |
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E.4 | Principal exclusion criteria |
Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy. • Known contra-indication to muscle biopsy (such as bleeding or clotting disorders). • Prior or ongoing therapy with ataluren. • Known hypersensitivity to any of the ingredients or excipients of the study drug (for example, refined polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, colloidal silica, magnesium stearate). • Exposure to another investigational drug within 2 months prior to start of study treatment, or ongoing participation in any interventional clinical trial. • Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy. Evening non-invasive mechanical ventilation such as use of bilevel positive airway pressure (Bi-PAP) therapy is allowed. • Elevated serum creatinine or cystatin C levels at screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent Change From Baseline in Dystrophin Levels at Week 40, as Measured by ECL |
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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) |
Percent Change From Baseline in Dystrophin Levels/Intensity at Week 40, as Determined by a Validated Immunohistochemistry Assay |
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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 | Yes |
E.6.6 | Pharmacokinetic | No |
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) | 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.8.3 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |