Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

• ClinicalTrials.gov Identifier: NCT03179631
• Recruitment Status: Active, not recruiting
• First Posted: June 7, 2017
• Last Update Posted: February 16, 2023
• Sponsor: PTC Therapeutics
• Information provided by (Responsible Party): PTC Therapeutics

Tracking Information

• First Submitted Date: June 1, 2017
• First Posted Date: June 7, 2017
• Last Update Posted Date: February 16, 2023
• Actual Study Start Date: July 6, 2017
• Actual Primary Completion Date: March 5, 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 23, 2018): Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks [ Time Frame: 72 weeks ]
• Original Primary Outcome Measures (submitted: June 5, 2017): 6- Minute Walk Test [ Time Frame: 72 weeks ]

Current Secondary Outcome Measures (submitted: October 23, 2018)

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

Original Secondary Outcome Measures (submitted: June 5, 2017)

• Timed Function Tests [ Time Frame: 72 weeks ]
• North Star Ambulatory Assessment [ Time Frame: 72 weeks ]
• Performance of Upper Limb (in patients >=7 years old at baseline) [ Time Frame: 72 weeks ]
• Myometry (in patients <7 years old at baseline) [ Time Frame: 72 weeks ]
• Magnetic Resonance Imaging (MRI) (at pre-qualified sites) [ Time Frame: 72 weeks ]
• EQ-5D [ Time Frame: 72 weels ]
• Ataluren safety profile characterized by adverse events and abnormalities of laboratory tests, vital signs, physical examinations, or electrocardiograms [ Time Frame: 72 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy and Open-Label Extension
• 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 Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This study describes the randomized, double-blind, placebo-controlled, 72-week study and its 72-week open-label extension

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

A randomized, double-blind, placebo-controlled,72-week study and its 72-week open-label extension

Primary Purpose: Treatment

Condition

• Muscular Dystrophy, Duchenne
• Muscular Dystrophies
• Muscular Disorders, Atrophic
• Muscular Diseases
• Musculoskeletal Disease
• Neuromuscular Diseases
• Nervous System Diseases
• Genetic Diseases, X-Linked
• Genetic Diseases, Inborn

Intervention

• Drug: Ataluren
  10, 20 mg/kg
  Other Name: PTC124
• Drug: PLACEBO
  10, 20 mg/kg
  Other Name: Matching Placebo

Study Arms

• Experimental: Ataluren
  10, 20 milligrams per kilogram (mg/kg)
  Intervention: Drug: Ataluren
• Placebo Comparator: Placebo
  10, 20 mg/kg
  Intervention: Drug: PLACEBO

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 4, 2022): 360
• Original Estimated Enrollment (submitted: June 5, 2017): 250
• Estimated Study Completion Date: July 20, 2023
• Actual Primary Completion Date: March 5, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male

• Ages: 5 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Brazil, Bulgaria, Canada, China, Hong Kong, India, Japan, Korea, Republic of, Malaysia, Mexico, Poland, Puerto Rico, Russian Federation, Taiwan, Thailand, Turkey, United States
• Removed Location Countries: Argentina, Chile, Jordan, Sri Lanka

Administrative Information

• NCT Number: NCT03179631
• Other Study ID Numbers: PTC124-GD-041-DMD
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: PTC Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: PTC Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Vinay Penematsa, MD; PTC Therapeutics, Inc.

• PRS Account: PTC Therapeutics
• Verification Date: February 2023