Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

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

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

Study Overview

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

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
• Enrollment (Actual): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Brisbane, Australia, Q4101
    • Queensland Children's Hospital
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • The Childrens Hospital at Westmead
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • The Royal Childrens Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perth Children's Hospital
• Brazil
  • Belo Horizonte, Brazil, 30130-100
    • Hospital de Clínicas da Universidade Federal de Minas Gerais
  • Rio De Janeiro, Brazil, 21.941-912
    • Universidade Federal do Rio de Janeiro
  • São Paulo, Brazil, 05403-000
    • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
• Bulgaria
  • Sofia, Bulgaria, 1793
    • UMHAT Sofiamed
• Canada
  • Ontario
    • London, Ontario, Canada, N6A5W9
      • Childrens Hospital London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H8L1
      • Childrens Hospital of Eastern Ontario
• China
  • Beijing, China, 100039
    • General Hospital of Chinese Armed Police Forces
  • Fuzhou, China, 350005
    • The First Affiliated Hospital Of Fujian Medical University
  • Hunan, China, 410008
    • Xiangya Hospital Central South University
  • Shanghai, China, 200032
    • Children's Hospital of Fudan University
  • Shenzhen, China, 518038
    • Shenzhen Children's Hospital
• Hong Kong
  • Hong Kong, Hong Kong, SAR
    • Queen Mary Hospital
• India
  • Chandigarh, India, 160012
    • Postgraduate Institute of Medical Education and Research
  • New Delhi, India, 110029
    • All India Institute of Medical Sciences
  • Gujarat
    • Ahmedabad, Gujarat, India, 380005
      • Panchshil hospital
  • Karnataka
    • Bengaluru, Karnataka, India, 560029
      • National Institute of Mental Health and Neurosciences
  • Maharashtra
    • Mahim, Maharashtra, India, 400016
      • P.D. Hinduja Hospital
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600006
      • Apollo Children's Hospital Chennai
    • Vellore, Tamil Nadu, India, 632004
      • Christian Medical College Hospital Vellore
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Nizam's Institute of Medical Sciences (NIMS)
  • West Bengal
    • Kolkata, West Bengal, India, 700054
      • Apollo Gleneagles Hospital
• Japan
  • Multiple Locations, Japan
    • PTC Clinical Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Gyeongsangnamdo
    • Yangsan, Gyeongsangnamdo, Korea, Republic of, 50612
      • Pusan National University Yangsan Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Tunku Azizah Kuala Lumpur
  • Pantai, Malaysia, 59100
    • University Malaya Medical Centre (UMMC)
• Mexico
  • Chihuahua, Mexico, 31217
    • Hospital Angeles Chihuahua
  • Ciudad de mexico, Mexico, 04530
    • Instituto Nacional de Pediatria
  • Tlalpan, Mexico, 14389
    • Instituto Nacional De Rehabilitacion
• Poland
  • Warszawa, Poland, 02-097
    • Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
• Puerto Rico
  • San Juan, Puerto Rico, 00936-5067
    • University of Puerto Rico - School of Medicine
• Russian Federation
  • Moscow, Russian Federation, 125412
    • Russian National Research Medical University n.a. N.I.Pirogov, structural branch - Research Clinical Institute of Pediatrics n.a. Academician Yu. E. Veltishchev
  • Saint Petersburg, Russian Federation, 194100
    • "Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
• Turkey
  • Istanbul, Turkey, 34093
    • Istanbul University- Instanbul Medical Faculty
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Childrens Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Oakland, California, United States, 94143
      • University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center
    • Sacramento, California, United States, 95817
      • University of California (UC) Davis Medical Center
    • San Bernardino, California, United States, 92408
      • Loma Linda University Children'S Hospital
  • Florida
    • Gulf Breeze, Florida, United States, 32561
      • Northwest Florida Clinical Research Group, LLC
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health - Riley Child Neurology
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan - CS Mott Children's Hospital
    • Detroit, Michigan, United States, 48201
      • Children's Hospital of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • New York
    • New York, New York, United States, 10032
      • Columbia University College of Physicians & Surgeons
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Shriners Hospital for Children
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh School of Medicine
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Childrens Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas Health Science Center at San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ataluren; 10, 20 milligrams per kilogram (mg/kg)	Drug: Ataluren; 10, 20 mg/kg; Other Names: PTC124
Placebo Comparator: Placebo; 10, 20 mg/kg	Drug: PLACEBO; 10, 20 mg/kg; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks	72 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• References

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2017
• Primary Completion (Actual): March 5, 2022
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: June 1, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (Actual): June 7, 2017

Study Record Updates

• Last Update Posted (Estimated): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy; Ataluren; PTC124; Becker Muscular Dystrophy; Dystrophinopathy; Nonsense Mutation; Premature Stop Codon; DMD/BMD
• Additional Relevant MeSH Terms: Muscular Dystrophies; Nervous System Diseases; Musculoskeletal Diseases; Muscular Diseases; Muscular Dystrophy, Duchenne; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Neuromuscular Diseases; Muscular Disorders, Atrophic
• Other Study ID Numbers: PTC124-GD-041-DMD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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