Back to resultsLong-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
Primary Purpose
Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Ataluren
PLACEBO
Sponsored by
About this trial
This is an interventional treatment trial for Muscular Dystrophy, Duchenne focused on measuring Duchenne Muscular Dystrophy, Dystrophinopathy, Nonsense Mutation, Premature Stop Codon, Becker Muscular Dystrophy, DMD/BMD, PTC124, Ataluren
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.
Sites / Locations
- Phoenix Childrens Hospital
- Children's Hospital of Los Angeles
- University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland
- Stanford University Medical Center
- University of California (UC) Davis Medical Center
- Loma Linda University Children's Hospital
- Northwest Florida Clinical Research Group, LLC
- Indiana University Health - Riley Child Neurology
- University of Kansas Medical Center
- University of Michigan - CS Mott Children's Hospital
- Children's Hospital of Michigan
- University of Minnesota
- Columbia University College of Physicians & Surgeons
- Cincinnati Children's Hospital Medical Center
- Shriners Hospital for Children
- University of Pittsburgh School of Medicine
- Cook Childrens Medical Center
- Texas Children's Hospital
- University of Texas Health Science Center at San Antonio
- University Of Utah
- Children's Hospital of the King's Daughters
- Seattle Children's Hospital
- The Childrens Hospital at Westmead
- The Royal Childrens Hospital
- Perth Children's Hospital
- Queensland Children's Hospital
- Hospital de Clínicas da Universidade Federal de Minas Gerais
- Universidade Federal do Rio de Janeiro
- Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
- UMHAT Sofiamed
- Childrens Hospital London Health Sciences Centre
- Childrens Hospital of Eastern Ontario
- General Hospital of Chinese Armed Police Forces
- The First Affiliated Hospital of Fujian Medical University
- Xiangya Hospital Central South University
- Children's Hospital of Fudan University
- Shenzhen Children's Hospital
- Queen Mary Hospital
- Panchshil Hospital
- National Institute of Mental Health and Neurosciences
- P.D. Hinduja Hospital
- Apollo Children's Hospital Chennai
- Christian Medical College Hospital Vellore
- Nizam's Institute of Medical Sciences (NIMS)
- Apollo Gleneagles Hospital
- Postgraduate Institute of Medical Education and Research
- All India Institute of Medical Sciences
- National Hospital Organization Higashisaitama National Hospital
- National Center of Neurology and Psychiatry
- Kumamoto University Hospital
- Kyoto University Hospital
- Nagoya City University Hospital
- Hyogo College of Medicine Hospital
- Miyagi Children's Hospital
- National Hospital Organization Toneyama National Hospital
- Tottori University Hospital
- Pusan National University Yangsan Hospital
- Samsung Medical Center
- Seoul National University Hospital
- Hospital Tunku Azizah Kuala Lumpur
- University Malaya Medical Centre (UMMC)
- Hospital Angeles Chihuahua
- Instituto Nacional de Pediatría
- Instituto Nacional de Rehabilitacion
- Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
- University of Puerto Rico - School of Medicine
- 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 State Paediatric Medical University" based at Consultative and Diagnostic Centre
- Kaohsiung Medical University Chung-Ho Memorial Hospital
- National Taiwan University Hospital
- Siriraj Hospital
- Istanbul University- Instanbul Medical Faculty
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Ataluren
Placebo
Arm Description
10, 20 milligrams per kilogram (mg/kg)
10, 20 mg/kg
Outcomes
Primary Outcome Measures
Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks
Secondary Outcome Measures
Change from Baseline to Week 72 in 6MWD
Change from Baseline to Week 72 in Time to Run/Walk 10 Meters
Change from Baseline to Week 72 in Time to Climb 4 Stairs
Change from Baseline to Week 72 in Time to Descend 4 Stairs
Change from Baseline to Week 72 in North Start Ambulatory Assessment (NSAA) Total Score
Time to Loss of Ambulation Over 72 Weeks
Time to Loss of Stair-Climbing Over 72 Weeks
Time to Loss of Stair-Descending Over 72 Weeks
Risk of Loss of NSAA Items Over 72 weeks
Number of Treatment-Emergent Adverse Events Considered Related to Study Drug
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03179631
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
July 6, 2017 (Actual)
Primary Completion Date
March 5, 2022 (Actual)
Study Completion Date
July 25, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PTC Therapeutics
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
This study describes the randomized, double-blind, placebo-controlled, 72-week study and its 72-week open-label extension
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
A randomized, double-blind, placebo-controlled,72-week study and its 72-week open-label extension
Allocation
Randomized
Enrollment
360 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ataluren
Arm Type
Experimental
Arm Description
10, 20 milligrams per kilogram (mg/kg)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
10, 20 mg/kg
Intervention Type
Drug
Intervention Name(s)
Ataluren
Other Intervention Name(s)
PTC124
Intervention Description
10, 20 mg/kg
Intervention Type
Drug
Intervention Name(s)
PLACEBO
Other Intervention Name(s)
Matching Placebo
Intervention Description
10, 20 mg/kg
Primary Outcome Measure Information:
Title
Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks
Time Frame
72 weeks
Secondary Outcome Measure Information:
Title
Change from Baseline to Week 72 in 6MWD
Time Frame
Baseline, Week 72
Title
Change from Baseline to Week 72 in Time to Run/Walk 10 Meters
Time Frame
Baseline, Week 72
Title
Change from Baseline to Week 72 in Time to Climb 4 Stairs
Time Frame
Baseline, Week 72
Title
Change from Baseline to Week 72 in Time to Descend 4 Stairs
Time Frame
Baseline, Week 72
Title
Change from Baseline to Week 72 in North Start Ambulatory Assessment (NSAA) Total Score
Time Frame
Baseline, Week 72
Title
Time to Loss of Ambulation Over 72 Weeks
Time Frame
72 weeks
Title
Time to Loss of Stair-Climbing Over 72 Weeks
Time Frame
72 Weeks
Title
Time to Loss of Stair-Descending Over 72 Weeks
Time Frame
72 weeks
Title
Risk of Loss of NSAA Items Over 72 weeks
Time Frame
72 weels
Title
Number of Treatment-Emergent Adverse Events Considered Related to Study Drug
Time Frame
72 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
5 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vinay Penematsa, MD
Organizational Affiliation
PTC Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Phoenix Childrens Hospital
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85016
Country
United States
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Stanford University Medical Center
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of California (UC) Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Loma Linda University Children's Hospital
City
San Bernardino
State/Province
California
ZIP/Postal Code
92408
Country
United States
Facility Name
Northwest Florida Clinical Research Group, LLC
City
Gulf Breeze
State/Province
Florida
ZIP/Postal Code
32561
Country
United States
Facility Name
Indiana University Health - Riley Child Neurology
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
University of Michigan - CS Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Columbia University College of Physicians & Surgeons
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Shriners Hospital for Children
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pittsburgh School of Medicine
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Cook Childrens Medical Center
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
Facility Name
University Of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Facility Name
Children's Hospital of the King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
The Childrens Hospital at Westmead
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Facility Name
The Royal Childrens Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
Facility Name
Perth Children's Hospital
City
Nedlands
State/Province
Western Australia
ZIP/Postal Code
6009
Country
Australia
Facility Name
Queensland Children's Hospital
City
South Brisbane
ZIP/Postal Code
Q4101
Country
Australia
Facility Name
Hospital de Clínicas da Universidade Federal de Minas Gerais
City
Belo Horizonte
ZIP/Postal Code
30130-100
Country
Brazil
Facility Name
Universidade Federal do Rio de Janeiro
City
Rio De Janeiro
ZIP/Postal Code
21.941-912
Country
Brazil
Facility Name
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo - FMUSP
City
São Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
UMHAT Sofiamed
City
Sofia
ZIP/Postal Code
1793
Country
Bulgaria
Facility Name
Childrens Hospital London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A5W9
Country
Canada
Facility Name
Childrens Hospital of Eastern Ontario
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H8L1
Country
Canada
Facility Name
General Hospital of Chinese Armed Police Forces
City
Beijing
ZIP/Postal Code
100039
Country
China
Facility Name
The First Affiliated Hospital of Fujian Medical University
City
Fuzhou
ZIP/Postal Code
350005
Country
China
Facility Name
Xiangya Hospital Central South University
City
Hunan
ZIP/Postal Code
410008
Country
China
Facility Name
Children's Hospital of Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Shenzhen Children's Hospital
City
Shenzhen
ZIP/Postal Code
518038
Country
China
Facility Name
Queen Mary Hospital
City
Hong Kong
ZIP/Postal Code
SAR
Country
Hong Kong
Facility Name
Panchshil Hospital
City
Ahmedabad
State/Province
Gujarat
ZIP/Postal Code
380005
Country
India
Facility Name
National Institute of Mental Health and Neurosciences
City
Bengaluru
State/Province
Karnataka
ZIP/Postal Code
560029
Country
India
Facility Name
P.D. Hinduja Hospital
City
Mahim
State/Province
Maharashtra
ZIP/Postal Code
400016
Country
India
Facility Name
Apollo Children's Hospital Chennai
City
Chennai
State/Province
Tamil Nadu
ZIP/Postal Code
600006
Country
India
Facility Name
Christian Medical College Hospital Vellore
City
Vellore
State/Province
Tamil Nadu
ZIP/Postal Code
632004
Country
India
Facility Name
Nizam's Institute of Medical Sciences (NIMS)
City
Hyderabad
State/Province
Telangana
ZIP/Postal Code
500082
Country
India
Facility Name
Apollo Gleneagles Hospital
City
Kolkata
State/Province
West Bengal
ZIP/Postal Code
700054
Country
India
Facility Name
Postgraduate Institute of Medical Education and Research
City
Chandigarh
ZIP/Postal Code
160012
Country
India
Facility Name
All India Institute of Medical Sciences
City
New Delhi
ZIP/Postal Code
110029
Country
India
Facility Name
National Hospital Organization Higashisaitama National Hospital
City
Hasuda-city
Country
Japan
Facility Name
National Center of Neurology and Psychiatry
City
Kodaira
Country
Japan
Facility Name
Kumamoto University Hospital
City
Kumamoto-shi
Country
Japan
Facility Name
Kyoto University Hospital
City
Kyoto
Country
Japan
Facility Name
Nagoya City University Hospital
City
Nagoya-shi
Country
Japan
Facility Name
Hyogo College of Medicine Hospital
City
Nishinomiya
Country
Japan
Facility Name
Miyagi Children's Hospital
City
Sendai
Country
Japan
Facility Name
National Hospital Organization Toneyama National Hospital
City
Toyonaka-shi
Country
Japan
Facility Name
Tottori University Hospital
City
Yonago
Country
Japan
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
State/Province
Gyeongsangnamdo
ZIP/Postal Code
50612
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
3080
Country
Korea, Republic of
Facility Name
Hospital Tunku Azizah Kuala Lumpur
City
Kuala Lumpur
ZIP/Postal Code
50586
Country
Malaysia
Facility Name
University Malaya Medical Centre (UMMC)
City
Pantai
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Hospital Angeles Chihuahua
City
Chihuahua
ZIP/Postal Code
31217
Country
Mexico
Facility Name
Instituto Nacional de Pediatría
City
Ciudad de mexico
ZIP/Postal Code
04530
Country
Mexico
Facility Name
Instituto Nacional de Rehabilitacion
City
Tlalpan
ZIP/Postal Code
14389
Country
Mexico
Facility Name
Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
University of Puerto Rico - School of Medicine
City
San Juan
ZIP/Postal Code
00936-5067
Country
Puerto Rico
Facility Name
Russian National Research Medical University n.a. N.I.Pirogov, structural branch - Research Clinical Institute of Pediatrics n.a. Academician Yu. E. Veltishchev
City
Moscow
ZIP/Postal Code
125412
Country
Russian Federation
Facility Name
"Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre
City
Saint Petersburg
ZIP/Postal Code
194100
Country
Russian Federation
Facility Name
Kaohsiung Medical University Chung-Ho Memorial Hospital
City
Kaohsiung
ZIP/Postal Code
80756
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Siriraj Hospital
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Istanbul University- Instanbul Medical Faculty
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://www.ptcbio.com
Description
References
Learn more about this trial
Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy
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