A Study to Assess Dystrophin Levels in Participants With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD)

Phase 2 Clinical Pharmacology Study to Assess Dystrophin Levels in Subjects With nmDMD Before and After Treatment With Ataluren

This study is designed to evaluate the ability of ataluren to increase dystrophin protein levels in muscle cells of participants with nmDMD. The study will evaluate the levels of dystrophin before and after 40 weeks of ataluren therapy using muscle biopsies and 2 validated assay methods, electrochemiluminescence (ECL) and immunohistochemistry.

Study Overview

• Status: Completed
• Conditions: Duchenne Muscular Dystrophy
• Intervention / Treatment: Drug: Ataluren

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Los Angeles, California, United States, 90025
      • University of California, Los Angeles (UCLA)
    • Sacramento, California, United States, 95817
      • University of California (UC) Davis Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10032
      • Columbia University College of Physicians & Surgeons
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Heath Science Center at San Antonio
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 7 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.
• 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). Medical documentation of phenotypic evidence of DMD needs to be provided upon request by the Sponsor's medical monitor.
• Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing. Review and approval of documentation by sponsor or designee is required prior to enrollment.
• Willing to undergo muscle biopsy.

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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ataluren; Participants will receive ataluren oral suspension 10 milligrams per kilogram (mg/kg) in the morning, 10 mg/kg at midday, and 20 mg/kg in the evening each day for 40 weeks.	Drug: Ataluren; Ataluren will be administered as per the dose and schedule specified in the arm.; Other Names: PTC124

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Dystrophin Level at Week 40, as Measured by ECL	The percent change in dystrophin level from baseline in ambulatory nonsense mutation duchenne muscular dystrophy (nmDMD) participants after treatment with ataluren for 40 weeks was analyzed using quantitative assay (ECL).The least square (LS) mean and 90% confidence interval (CI) were analyzed from a mixed-model repeated measures (MMRM) with factors of muscle locations and visits as fixed effects, and participants as a random effect.	Baseline, Week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Dystrophin Level at Week 40, as Determined by Immunohistochemistry (IHC) Membrane Stain Density	The percent change in dystrophin level from baseline in ambulatory nmDMD participants after 40 weeks of ataluren therapy was determined by IHC membrane stain density. The LS mean and 90% CI were analyzed from an MMRM with factors of muscle locations and visits as fixed effects, and participants as a random effect.	Baseline, Week 40

Collaborators and Investigators

• Sponsor: PTC Therapeutics
• Investigators: Study Director: Francesco Bibbiani, MD, PTC Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Actual): October 23, 2020
• Study Completion (Actual): October 23, 2020

Study Registration Dates

• First Submitted: August 24, 2018
• First Submitted That Met QC Criteria: August 24, 2018
• First Posted (Actual): August 27, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: PTC124-GD-045-DMD; 2019-001767-67 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No