Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

Nervous System Diseases Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03179631
• Other study ID #: PTC124-GD-041-DMD
• Status: Completed
• Phase: Phase 3
• Start date: July 6, 2017
• Est. completion date: July 25, 2023

Study information

• Verified date: January 2024
• Source: PTC Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: July 25, 2023
• Est. primary completion date: March 5, 2022
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ataluren
10, 20 mg/kg
• PLACEBO
10, 20 mg/kg

Locations

Country	Name	City	State
Australia	Perth Children's Hospital	Nedlands	Western Australia
Australia	The Royal Childrens Hospital	Parkville	Victoria
Australia	Queensland Children's Hospital	South Brisbane
Australia	The Childrens Hospital at Westmead	Westmead	New South Wales
Brazil	Hospital de Clínicas da Universidade Federal de Minas Gerais	Belo Horizonte
Brazil	Universidade Federal do Rio de Janeiro	Rio De Janeiro
Brazil	Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP	São Paulo
Bulgaria	UMHAT Sofiamed	Sofia
Canada	Childrens Hospital London Health Sciences Centre	London	Ontario
Canada	Childrens Hospital of Eastern Ontario	Ottawa	Ontario
China	General Hospital of Chinese Armed Police Forces	Beijing
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou
China	Xiangya Hospital Central South University	Hunan
China	Children's Hospital of Fudan University	Shanghai
China	Shenzhen Children's Hospital	Shenzhen
Hong Kong	Queen Mary Hospital	Hong Kong
India	Panchshil Hospital	Ahmedabad	Gujarat
India	National Institute of Mental Health and Neurosciences	Bengaluru	Karnataka
India	Postgraduate Institute of Medical Education and Research	Chandigarh
India	Apollo Children's Hospital Chennai	Chennai	Tamil Nadu
India	Nizam's Institute of Medical Sciences (NIMS)	Hyderabad	Telangana
India	Apollo Gleneagles Hospital	Kolkata	West Bengal
India	P.D. Hinduja Hospital	Mahim	Maharashtra
India	All India Institute of Medical Sciences	New Delhi
India	Christian Medical College Hospital Vellore	Vellore	Tamil Nadu
Japan	PTC Clinical Site	Multiple Locations
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan	Gyeongsangnamdo
Malaysia	Hospital Tunku Azizah Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre (UMMC)	Pantai
Mexico	Hospital Angeles Chihuahua	Chihuahua
Mexico	Instituto Nacional de Pediatría	Ciudad de mexico
Mexico	Instituto Nacional de Rehabilitacion	Tlalpan
Poland	Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie	Warszawa
Puerto Rico	University of Puerto Rico - School of Medicine	San Juan
Russian Federation	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	"Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre	Saint Petersburg
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Thailand	Siriraj Hospital	Bangkok
Turkey	Istanbul University- Instanbul Medical Faculty	Istanbul
United States	University of Michigan - CS Mott Children's Hospital	Ann Arbor	Michigan
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Cook Childrens Medical Center	Fort Worth	Texas
United States	Northwest Florida Clinical Research Group, LLC	Gulf Breeze	Florida
United States	Texas Children's Hospital	Houston	Texas
United States	Indiana University Health - Riley Child Neurology	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	University of Minnesota	Minneapolis	Minnesota
United States	Columbia University College of Physicians & Surgeons	New York	New York
United States	Children's Hospital of the King's Daughters	Norfolk	Virginia
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	Phoenix Childrens Hospital	Phoenix	Arizona
United States	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania
United States	Shriners Hospital for Children	Portland	Oregon
United States	University of California (UC) Davis Medical Center	Sacramento	California
United States	University Of Utah	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Loma Linda University Children's Hospital	San Bernardino	California
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Bulgaria,  Canada,  China,  Hong Kong,  India,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Poland,  Puerto Rico,  Russian Federation,  Taiwan,  Thailand,  Turkey, 

Outcome

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

External Links

•   References