Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
- Conditions
- Nervous System DiseasesMuscular Dystrophy, DuchenneMuscular DystrophiesMusculoskeletal DiseaseGenetic Diseases, InbornMuscular DiseasesNeuromuscular DiseasesGenetic Diseases, X-LinkedMuscular Disorders, Atrophic
- Interventions
- Drug: PLACEBO
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 360
- 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.
- 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 Time to Loss of Ambulation Over 72 Weeks 72 weeks 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
Trial Locations
- Locations (64)
Stanford University Medical Center
🇺🇸Palo Alto, California, United States
Queensland Children's Hospital
🇦🇺South Brisbane, Australia
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Instituto Nacional de Pediatría
🇲🇽Ciudad de mexico, Mexico
"Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre
🇷🇺Saint Petersburg, Russian Federation
Siriraj Hospital
🇹🇭Bangkok, Thailand
Hospital de Clínicas da Universidade Federal de Minas Gerais
🇧🇷Belo Horizonte, Brazil
The Royal Childrens Hospital
🇦🇺Parkville, Victoria, Australia
P.D. Hinduja Hospital
🇮🇳Mahim, Maharashtra, India
Postgraduate Institute of Medical Education and Research
🇮🇳Chandigarh, India
Russian National Research Medical University n.a. N.I.Pirogov, structural branch - Research Clinical Institute of Pediatrics n.a. Academician Yu. E. Veltishchev
🇷🇺Moscow, Russian Federation
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
University Malaya Medical Centre (UMMC)
🇲🇾Pantai, Malaysia
Hospital Angeles Chihuahua
🇲🇽Chihuahua, Mexico
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland
🇺🇸Oakland, California, United States
Loma Linda University Children's Hospital
🇺🇸San Bernardino, California, United States
Indiana University Health - Riley Child Neurology
🇺🇸Indianapolis, Indiana, United States
Columbia University College of Physicians & Surgeons
🇺🇸New York, New York, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
University Of Utah
🇺🇸Salt Lake City, Utah, United States
Christian Medical College Hospital Vellore
🇮🇳Vellore, Tamil Nadu, India
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Perth Children's Hospital
🇦🇺Nedlands, Western Australia, Australia
Apollo Children's Hospital Chennai
🇮🇳Chennai, Tamil Nadu, India
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Phoenix Childrens Hospital
🇺🇸Phoenix, Arizona, United States
University of California (UC) Davis Medical Center
🇺🇸Sacramento, California, United States
University of Michigan - CS Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Shriners Hospital for Children
🇺🇸Portland, Oregon, United States
Northwest Florida Clinical Research Group, LLC
🇺🇸Gulf Breeze, Florida, United States
University of Pittsburgh School of Medicine
🇺🇸Pittsburgh, Pennsylvania, United States
The Childrens Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Children's Hospital of the King's Daughters
🇺🇸Norfolk, Virginia, United States
Universidade Federal do Rio de Janeiro
🇧🇷Rio De Janeiro, Brazil
UMHAT Sofiamed
🇧🇬Sofia, Bulgaria
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
🇧🇷São Paulo, Brazil
Childrens Hospital London Health Sciences Centre
🇨🇦London, Ontario, Canada
Childrens Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
General Hospital of Chinese Armed Police Forces
🇨🇳Beijing, China
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, China
Children's Hospital of Fudan University
🇨🇳Shanghai, China
Panchshil Hospital
🇮🇳Ahmedabad, Gujarat, India
Xiangya Hospital Central South University
🇨🇳Hunan, China
Shenzhen Children's Hospital
🇨🇳Shenzhen, China
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
National Institute of Mental Health and Neurosciences
🇮🇳Bengaluru, Karnataka, India
Nizam's Institute of Medical Sciences (NIMS)
🇮🇳Hyderabad, Telangana, India
Apollo Gleneagles Hospital
🇮🇳Kolkata, West Bengal, India
All India Institute of Medical Sciences
🇮🇳New Delhi, India
PTC Clinical Site
🇯🇵Multiple Locations, Japan
Hospital Tunku Azizah Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Gyeongsangnamdo, Korea, Republic of
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
🇵🇱Warszawa, Poland
University of Puerto Rico - School of Medicine
🇵🇷San Juan, Puerto Rico
Instituto Nacional de Rehabilitacion
🇲🇽Tlalpan, Mexico
Istanbul University- Instanbul Medical Faculty
🇹🇷Istanbul, Turkey
Cook Childrens Medical Center
🇺🇸Fort Worth, Texas, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States