Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03179631
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : February 21, 2018
Information provided by (Responsible Party):
PTC Therapeutics

Brief Summary:
This study is a long-term study of ataluren in patients with nonsense mutation Duchenne muscular dystrophy.

Condition or disease Intervention/treatment Phase
Muscular Dystrophy, Duchenne Muscular Dystrophies Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Disease Neuromuscular Diseases Nervous System Diseases Genetic Diseases, X-Linked Genetic Diseases, Inborn Drug: Ataluren Drug: PLACEBO Phase 3

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. Patients will be randomized in a 1:1 ratio to ataluren or placebo. Patients will receive blinded study drug TID at morning, midday, and evening for 72 weeks, after which all patients 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 6MWD >=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  (Clinical Trial)
Estimated Enrollment : 250 participants
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
Official Title: A Phase 3 Randomized Double Blind Placebo Controlled Efficacy and Safety Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy (nmDMD) and Open Label Extension
Actual Study Start Date : July 6, 2017
Estimated Primary Completion Date : March 2020
Estimated Study Completion Date : December 2021

Arm Intervention/treatment
Experimental: Ataluren
10, 10, 20 mg/kg
Drug: Ataluren
10, 10, 20 mg/kg
Other Name: PTC124
Placebo Comparator: Placebo
10, 10, 20 mg/kg
10, 10, 20 mg/kg
Other Name: Matching Placebo

Primary Outcome Measures :
  1. 6- Minute Walk Test [ Time Frame: 72 weeks ]

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   5 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria -

  • Male sex.
  • Age ≥5 years.
  • Phenotypic evidence of DMD
  • 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.
  • Prior or 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03179631

Contact: Mary Frances Harmon 908-912-9256
Contact: Amy Perniciaro 908-912-9264

  Hide Study Locations
United States, California
Stanford University Medical Center Recruiting
Palo Alto, California, United States, 94305
Contact: Carolyn McLaughlin Savage    650-206-3178   
Principal Investigator: John Day, MD         
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Contact: Novagrami George    203-785-5977   
Principal Investigator: Cristian Ionita, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Kiley Higgs    913-945-9922   
Principal Investigator: Jeffrey Statland, MD         
United States, Michigan
Children's Hospital of Michigan Recruiting
Detroit, Michigan, United States, 48201
Contact: Jamal Ameli    313-745-0627   
Principal Investigator: Huiyuan Jiang, MD         
United States, New York
Columbia University College of Physicians & Surgeons Recruiting
New York, New York, United States, 10032
Contact: Ameneh Onativia    212-342-3679   
Principal Investigator: Darryl De Vivo, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Sarah Wagner    513-803-9036   
Principal Investigator: Cuixia Tian, MD         
United States, Oregon
Shriners Hospital for Children Recruiting
Portland, Oregon, United States, 97239
Contact: Cassandra Black    971-282-4616   
Principal Investigator: Erika Finanger, MD         
United States, Texas
University of Texas Health Science Center at San Antonio Recruiting
San Antonio, Texas, United States, 78229-3900
Contact: Floyd Jones    210-567-8222   
Principal Investigator: Ratna Bhavaraju-Sanka, MD         
United States, Utah
University Of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Brittney Holmberg    801-585-9055   
Principal Investigator: Russell Butterfield, MD         
United States, Virginia
Children's Hospital of the King's Daughters Recruiting
Norfolk, Virginia, United States, 23507
Contact: Terrie Karras Conklin    757-469-9123   
Principal Investigator: Crystal Proud, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Ana Christensen    206-987-5433   
Principal Investigator: Susan Apkon, MD         
United States, Wisconsin
Prevea Clinic, Inc Recruiting
Green Bay, Wisconsin, United States, 54301
Contact: Cindy Quinnell    920-272-1044   
Principal Investigator: Terence Edgar, MD         
Australia, Victoria
The Royal Childrens Hospital Recruiting
Parkville, Victoria, Australia, 3052
Contact: Jemima Mitchell    +61 39936 6157   
Principal Investigator: Monique Ryan, MD         
UMHAT Sofiamed Recruiting
Sofia, Bulgaria, 1793
Contact: Elena Tzolova-Stamenova    359 888 771 652   
Principal Investigator: Velina Guergueltcheva, MD         
Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong, SAR
Contact: Amanda Mok    +852 2255 4538   
Principal Investigator: Sophelia Chan, MD         
Korea, Republic of
Pusan National University Yangsan Hospital Recruiting
Gyeongsang, Korea, Republic of, 50612
Contact: Jiyung Jeong   
Principal Investigator: Jin-Hong Shin, MD         
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 3080
Contact: Miae Kim    82-2-6072-5185   
Principal Investigator: Jong-Hee Chae, MD         
Pusan National University Yangsan Hospital Recruiting
Yangsan, Korea, Republic of, 50612
Contact: Jiyung Jeong    82 10 4747 3238   
Principal Investigator: Jin-Hong Shin, MD         
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 Recruiting
Moscow, Russian Federation, 125412
Contact: Svetlana Artemyeva    7 916-207-81-53   
Principal Investigator: Dmitry Vlodavets, MD         
Kaohsiung Medical University Chung-Ho Memorial Hospital Recruiting
Kaohsiung, Taiwan, 80756
Contact: Yun-Hui Chou    886 972 977 320   
Principal Investigator: Yuh-Jyh Jong, MD         
Sponsors and Collaborators
PTC Therapeutics
Study Director: Francesco Bibbiani, MD PTC Therapeutics, Inc.

Additional Information:
Responsible Party: PTC Therapeutics Identifier: NCT03179631     History of Changes
Other Study ID Numbers: PTC124-GD-041-DMD
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: February 21, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by PTC Therapeutics:
Duchenne Muscular Dystrophy
Nonsense Mutation
Premature Stop Codon
Becker Muscular Dystrophy

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Nervous System Diseases
Genetic Diseases, Inborn
Neuromuscular Diseases
Musculoskeletal Diseases
Muscular Diseases
Genetic Diseases, X-Linked
Muscular Disorders, Atrophic