A Study to Assess Dystrophin Levels in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) Who Have Been Treated With Ataluren

Study Overview
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Brief Summary
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This study is designed to generate additional data on the effect of ataluren for producing dystrophin protein in nonsense mutation nmDMD participants. This study will evaluate dystrophin levels from participants with nmDMD who currently have been receiving ataluren for ≥9 months. The study will have a single visit (Visit 1).

Official Title
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Phase 2, Non-Interventional, Clinical Study to Assess Dystrophin Levels in Subjects With Nonsense Mutation Duchenne Muscular Dystrophy Who Have Been Treated With Ataluren for ≥9 Months

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Ataluren


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Evidence of signed and dated informed consent/assent document(s) indicating that the participant (and/or his parent/legal guardian) has been informed of all pertinent aspects of the trial. Ambulatory (10 meters walk/run in less than [<] 30 seconds) and functional grade on the Brooke Upper Extremity Scale of a 1 or a 2. Currently being treated with ataluren 10, 10, 20 mg/kg for >=9 months, with no gap in treatment of greater than (>) 1 month, in an ongoing PTC-sponsored nmDMD clinical trial prior to study entry. 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) by 6 years of age and an elevated serum creatine kinase (CK). Medical documentation of phenotypic evidence of DMD needs to be provided upon request by the medical monitor. Willing to undergo muscle biopsy. Exclusion Criteria: Known contra-indication to muscle biopsy (such as bleeding or clotting disorders). Exposure to another investigational drug within 2 months prior to study enrollment or ongoing participation in any non-ataluren interventional clinical trial. Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy. Note: Evening non-invasive mechanical ventilation such as use of bilevel positive airway pressure (Bi-PAP) therapy is allowed. Prior or ongoing medical condition (for example, concomitant illness, psychiatric condition, behavioral disorder), medical history, physical findings or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the participant, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.
Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nmDMD Participants<br>Participants who have been receiving ataluren, will be dosed daily 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening, for >=9 months from ongoing PTC-sponsored nmDMD clinical trials. | Drug: Ataluren<br>* Ataluren will be administered as per the dose and schedule specified in the arm.<br>* Other names: PTC124;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Dystrophin Levels as Measured by Electrochemiluminescence (ECL) | The mean dystrophin protein levels were measured by ECL. Dystrophin levels are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). Results below the limit of quantitation were imputed as half of lower limit of quantitation (LLOQ). LLOQ = 0.5 micrograms (μg)/milliliter (mL) | Day 1 of biopsy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dystrophin Protein Levels as Determined by Immunohistochemistry | Dystrophin levels by IHC mean membrane stain density are reported by muscle group (gastrocnemius, tibialis anterior, and across muscle locations). | Day 1 of biopsy |