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

Duchenne Muscular Dystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03648827
• Other study ID #: PTC124-GD-045-DMD
• Secondary ID: 2019-001767-67
• Status: Completed
• Phase: Phase 2
• Start date: December 21, 2018
• Est. completion date: October 23, 2020

Study information

• Verified date: February 2022
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: October 23, 2020
• Est. primary completion date: October 23, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 2 Years to 7 Years

Eligibility

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.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Ataluren
Ataluren will be administered as per the dose and schedule specified in the arm.

Locations

Country	Name	City	State
United States	Texas Children's Hospital	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of California, Los Angeles (UCLA)	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University College of Physicians & Surgeons	New York	New York
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	University of California (UC) Davis Medical Center	Sacramento	California
United States	University of Texas Heath Science Center at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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