Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

Phase 3

Completed

• Conditions: Nervous System Diseases; Muscular Dystrophy, Duchenne; Muscular Dystrophies; Musculoskeletal Disease; Genetic Diseases, Inborn; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic
• Interventions: Drug: PLACEBO; Drug: Ataluren

• Registration Number: NCT03179631
• Lead Sponsor: PTC Therapeutics

Brief Summary

This study is a long-term study of ataluren in participants with nonsense mutation Duchenne muscular dystrophy.

Detailed Description

This study is a randomized, double-blind, placebo-controlled, 72-week study, followed by a 72-week open-label period. The purpose is to characterize the long-term effects of ataluren-mediated dystrophin restoration on disease progression. Participants will be randomized in a 1:1 ratio to ataluren or placebo. Participants will receive blinded study drug three times daily (TID) at morning, midday, and evening for 72 weeks, after which all participants will receive open-label ataluren for an additional 72 weeks (144 weeks in total). Study assessments will be performed at clinic visits every 12 weeks during the double-blind period and every 24 weeks during the open-label period. The total sample size of \~250 subjects will include \~160 subjects who meet the criteria for inclusion in the primary analysis population (age 7 to 16 years old, baseline six minute walk distance (6MWD) greater than or equal to (\>=) 300 meters, supine to stand \>= 5 seconds). The study will be conducted in the United States and other countries around the world.

Study Timeline

• Study First Submitted: 2017-06-01
• Study First Submitted QC: 2017-06-05
• Study First Posted: 2017-06-07
• Study Start: 2017-07-06
• Primary Completion: 2022-03-05
• Disposition First Submitted: 2023-02-09
• Disposition First Submitted QC: 2023-02-09
• Disposition First Posted: 2023-02-16
• Study Completion: 2023-07-25
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-16
• Last Update Posted: 2024-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 360

Inclusion Criteria

• Male sex
• Age ≥5 years
• Phenotypic evidence of Duchenne Muscular Dystrophy
• Nonsense point mutation in the dystrophin gene
• Use of systemic corticosteroids (prednisone/prednisolone or deflazacort)for a minimum of 12 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen for a minimum of 3 months immediately prior to start of study treatment
• 6MWD ≥150 meters
• Ability to perform timed function tests within 30 seconds
• Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria

• Any change in prophylaxis treatment for cardiomyopathy within 1 month prior to start of study treatment.
• Ongoing intravenous (IV) aminoglycoside or IV vancomycin therapy.
• Prior or ongoing therapy with ataluren.
• Known hypersensitivity to any of the ingredients or excipients of the study drug
• Exposure to another investigational drug within 6 months prior to start of study treatment, or ongoing participation in any interventional clinical trial.
• History of major surgical procedure within 12 weeks prior to start of study treatment, or expectation of major surgical procedure during the 72-week placebo-controlled treatment period.
• Requirement for daytime ventilator assistance or any use of invasive mechanical ventilation via tracheostomy.
• Uncontrolled clinical symptoms and signs of congestive heart failure
• Elevated serum creatinine or cystatin C at screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	PLACEBO	10, 20 mg/kg
Ataluren	Ataluren	10, 20 milligrams per kilogram (mg/kg)

Primary Outcome Measures

Name	Time	Method
Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks	72 weeks

Secondary Outcome Measures

Name	Time	Method
Change from Baseline to Week 72 in Time to Descend 4 Stairs	Baseline, Week 72
Time to Loss of Stair-Descending Over 72 Weeks	72 weeks
Change from Baseline to Week 72 in 6MWD	Baseline, Week 72
Change from Baseline to Week 72 in Time to Climb 4 Stairs	Baseline, Week 72
Time to Loss of Stair-Climbing Over 72 Weeks	72 Weeks
Risk of Loss of NSAA Items Over 72 weeks	72 weels
Change from Baseline to Week 72 in Time to Run/Walk 10 Meters	Baseline, Week 72
Change from Baseline to Week 72 in North Start Ambulatory Assessment (NSAA) Total Score	Baseline, Week 72
Number of Treatment-Emergent Adverse Events Considered Related to Study Drug	72 weeks
Time to Loss of Ambulation Over 72 Weeks	72 weeks

Trial Locations

Locations (64)

Phoenix Childrens Hospital; 🇺🇸 Phoenix, Arizona, United States

Children's Hospital of Los Angeles; 🇺🇸 Los Angeles, California, United States

University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland; 🇺🇸 Oakland, California, United States

Stanford University Medical Center; 🇺🇸 Palo Alto, California, United States

University of California (UC) Davis Medical Center; 🇺🇸 Sacramento, California, United States

Loma Linda University Children's Hospital; 🇺🇸 San Bernardino, California, United States

Northwest Florida Clinical Research Group, LLC; 🇺🇸 Gulf Breeze, Florida, United States

Indiana University Health - Riley Child Neurology; 🇺🇸 Indianapolis, Indiana, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States

University of Michigan - CS Mott Children's Hospital; 🇺🇸 Ann Arbor, Michigan, United States

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