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

NCT03648827 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: PTC124-GD-045-DMD2019-001767-67
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Duchenne Muscular Dystrophy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Percent Change From Baseline in Dystrophin Level at Week 40, as Determined by Immunohistochemistry (IHC) Membrane Stain Density

  Baseline, Week 40

Study Arms (1)

Ataluren

EXPERIMENTAL

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

Interventions

Ataluren DRUG

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

Also known as: PTC124

Ataluren

Eligibility Criteria

• Age: 2 Years - 7 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (9)

Phoenix Childrens Hospital

Phoenix, Arizona, 85016, United States

Location

University of California, Los Angeles (UCLA)

Los Angeles, California, 90025, United States

Location

University of California (UC) Davis Medical Center

Sacramento, California, 95817, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Columbia University College of Physicians & Surgeons

New York, New York, 10032, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Texas Heath Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23507, United States

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

ataluren

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Medical Information
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Study Officials

• Francesco Bibbiani, MD

  PTC Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2018
• First Posted: August 27, 2018
• Study Start: December 21, 2018
• Primary Completion: October 23, 2020
• Study Completion: October 23, 2020
• Last Updated: April 5, 2022
• Results First Posted: April 5, 2022

Record last verified: 2022-02

Locations

US (9)