Clinical trial NCT03179631: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Disease
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Keywords: Duchenne Muscular Dystrophy
Dystrophinopathy
Nonsense Mutation
Premature Stop Codon
Becker Muscular Dystrophy
DMD/BMD
PTC124
Ataluren
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-06-07
Enrollment: 360
Sex: MALE
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study describes the randomized, double-blind, placebo-controlled, 72-week study and its 72-week open-label extension
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks
timeFrame: 72 weeks
Secondary outcomes:
measure: Change from Baseline to Week 72 in 6MWD
timeFrame: Baseline, Week 72
measure: Change from Baseline to Week 72 in Time to Run/Walk 10 Meters
timeFrame: Baseline, Week 72
measure: Change from Baseline to Week 72 in Time to Climb 4 Stairs
timeFrame: Baseline, Week 72
measure: Change from Baseline to Week 72 in Time to Descend 4 Stairs
timeFrame: Baseline, Week 72
measure: Change from Baseline to Week 72 in North Start Ambulatory Assessment (NSAA) Total Score
timeFrame: Baseline, Week 72
measure: Time to Loss of Ambulation Over 72 Weeks
timeFrame: 72 weeks
measure: Time to Loss of Stair-Climbing Over 72 Weeks
timeFrame: 72 Weeks
measure: Time to Loss of Stair-Descending Over 72 Weeks
timeFrame: 72 weeks
measure: Risk of Loss of NSAA Items Over 72 weeks
timeFrame: 72 weels
measure: Number of Treatment-Emergent Adverse Events Considered Related to Study Drug
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Oakland
country: United States
facility: University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: Sacramento
country: United States
facility: University of California (UC) Davis Medical Center
state: California
city: San Bernardino
country: United States
facility: Loma Linda University Children's Hospital
state: California
city: Gulf Breeze
country: United States
facility: Northwest Florida Clinical Research Group, LLC
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health - Riley Child Neurology
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan - CS Mott Children's Hospital
state: Michigan
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: New York
country: United States
facility: Columbia University College of Physicians & Surgeons
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Shriners Hospital for Children
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine
state: Pennsylvania
city: Fort Worth
country: United States
facility: Cook Childrens Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University Of Utah
state: Utah
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughters
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Westmead
country: Australia
facility: The Childrens Hospital at Westmead
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Childrens Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Perth Children's Hospital
state: Western Australia
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Belo Horizonte
country: Brazil
facility: Hospital de Clínicas da Universidade Federal de Minas Gerais
city: Rio De Janeiro
country: Brazil
facility: Universidade Federal do Rio de Janeiro
city: São Paulo
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
city: Sofia
country: Bulgaria
facility: UMHAT Sofiamed
city: London
country: Canada
facility: Childrens Hospital London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Childrens Hospital of Eastern Ontario
state: Ontario
city: Beijing
country: China
facility: General Hospital of Chinese Armed Police Forces
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Hunan
country: China
facility: Xiangya Hospital Central South University
city: Shanghai
country: China
facility: Children's Hospital of Fudan University
city: Shenzhen
country: China
facility: Shenzhen Children's Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Ahmedabad
country: India
facility: Panchshil Hospital
state: Gujarat
city: Bengaluru
country: India
facility: National Institute of Mental Health and Neurosciences
state: Karnataka
city: Mahim
country: India
facility: P.D. Hinduja Hospital
state: Maharashtra
city: Chennai
country: India
facility: Apollo Children's Hospital Chennai
state: Tamil Nadu
city: Vellore
country: India
facility: Christian Medical College Hospital Vellore
state: Tamil Nadu
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences (NIMS)
state: Telangana
city: Kolkata
country: India
facility: Apollo Gleneagles Hospital
state: West Bengal
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
city: New Delhi
country: India
facility: All India Institute of Medical Sciences
city: Multiple Locations
country: Japan
facility: PTC Clinical Site
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
state: Gyeongsangnamdo
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Kuala Lumpur
country: Malaysia
facility: Hospital Tunku Azizah Kuala Lumpur
city: Pantai
country: Malaysia
facility: University Malaya Medical Centre (UMMC)
city: Chihuahua
country: Mexico
facility: Hospital Angeles Chihuahua
city: Ciudad de mexico
country: Mexico
facility: Instituto Nacional de Pediatría
city: Tlalpan
country: Mexico
facility: Instituto Nacional de Rehabilitacion
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico - School of Medicine
city: Moscow
country: Russian Federation
facility: Russian National Research Medical University n.a. N.I.Pirogov, structural branch - Research Clinical Institute of Pediatrics n.a. Academician Yu. E. Veltishchev
city: Saint Petersburg
country: Russian Federation
facility: "Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Istanbul
country: Turkey
facility: Istanbul University- Instanbul Medical Faculty
Study officials:
affiliation: PTC Therapeutics, Inc.
name: Vinay Penematsa, MD
role: STUDY_DIRECTOR
References: