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Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

Sponsor
PTC Therapeutics (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03179631
Collaborator
(none)
360
Enrollment
72
Locations
2
Arms
72.4
Anticipated Duration (Months)
5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
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. 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
360 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 extensionThis 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 and Open-Label Extension
Actual Study Start Date :
Jul 6, 2017
Anticipated Primary Completion Date :
May 1, 2022
Anticipated Study Completion Date :
Jul 20, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Ataluren

10, 20 milligrams per kilogram (mg/kg)

Drug: Ataluren
10, 20 mg/kg
Other Names:
  • PTC124

    		•
    Placebo Comparator: Placebo

    10, 20 mg/kg

    Drug: PLACEBO
    10, 20 mg/kg
    Other Names:
  • Matching Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Slope of Change in 6-Minute Walk Distance (6MWD) Over 72 Weeks [72 weeks]

    Secondary Outcome Measures

    1. Change from Baseline to Week 72 in 6MWD [Baseline, Week 72]

    2. Change from Baseline to Week 72 in Time to Run/Walk 10 Meters [Baseline, Week 72]

    3. Change from Baseline to Week 72 in Time to Climb 4 Stairs [Baseline, Week 72]

    4. Change from Baseline to Week 72 in Time to Descend 4 Stairs [Baseline, Week 72]

    5. Change from Baseline to Week 72 in North Start Ambulatory Assessment (NSAA) Total Score [Baseline, Week 72]

    6. Time to Loss of Ambulation Over 72 Weeks [72 weeks]

    7. Time to Loss of Stair-Climbing Over 72 Weeks [72 Weeks]

    8. Time to Loss of Stair-Descending Over 72 Weeks [72 weeks]

    9. Risk of Loss of NSAA Items Over 72 weeks [72 weels]

    10. Number of Treatment-Emergent Adverse Events Considered Related to Study Drug [72 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    5 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Phoenix Childrens Hospital Phoenix Arizona United States 85016
    2 Children's Hospital of Los Angeles Los Angeles California United States 90027
    3 University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland Oakland California United States 94143
    4 Stanford University Medical Center Palo Alto California United States 94305
    5 University of California (UC) Davis Medical Center Sacramento California United States 95817
    6 Loma Linda University Children's Hospital San Bernardino California United States 92408
    7 Child Neurology Center of Northwest Florida Gulf Breeze Florida United States 32561
    8 Indiana University Health - Riley Child Neurology Indianapolis Indiana United States 46202
    9 University of Kansas Medical Center Kansas City Kansas United States 66160
    10 University of Michigan - CS Mott Children's Hospital Ann Arbor Michigan United States 48109
    11 Children's Hospital of Michigan Detroit Michigan United States 48201
    12 University of Minnesota Minneapolis Minnesota United States 55455
    13 Columbia University College of Physicians & Surgeons New York New York United States 10032
    14 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
    15 Shriners Hospital for Children Portland Oregon United States 97239
    16 University of Pittsburgh School of Medicine Pittsburgh Pennsylvania United States 15224
    17 Cook Childrens Medical Center Fort Worth Texas United States 76104
    18 Texas Children's Hospital Houston Texas United States 77030
    19 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229-3900
    20 University Of Utah Salt Lake City Utah United States 84112
    21 Children's Hospital of the King's Daughters Norfolk Virginia United States 23507
    22 Seattle Children's Hospital Seattle Washington United States 98105
    23 The Childrens Hospital at Westmead Westmead New South Wales Australia 2145
    24 The Royal Childrens Hospital Parkville Victoria Australia 3052
    25 Perth Children's Hospital Nedlands Western Australia Australia 6009
    26 Queensland Children's Hospital South Brisbane Australia Q4101
    27 Hospital de Clínicas da Universidade Federal de Minas Gerais Belo Horizonte Brazil 30130-100
    28 Universidade Federal do Rio de Janeiro Rio De Janeiro Brazil 21.941-912
    29 Sao Paulo University São Paulo Brazil 05403-000
    30 UMHAT Sofiamed Sofia Bulgaria 1793
    31 Childrens Hospital London Health Sciences Centre London Ontario Canada N6A5W9
    32 Childrens Hospital of Eastern Ontario Ottawa Ontario Canada K1H8L1
    33 General Hospital of Chinese Armed Police Forces Beijing China 100039
    34 The First Affiliated Hospital of Fujian Medical University Fuzhou China 350005
    35 Xiangya Hospital Central South University Hunan China 410008
    36 Children's Hospital of Fudan University Shanghai China 200032
    37 Shenzhen Children's Hospital Shenzhen China 518038
    38 Queen Mary Hospital Hong Kong Hong Kong SAR
    39 Panchshil Hospital Ahmedabad Gujarat India 380005
    40 National Institute of Mental Health and Neurosciences Bengaluru Karnataka India 560029
    41 P.D. Hinduja Hospital Mahim Maharashtra India 400016
    42 Apollo Children's Hospital Chennai Chennai Tamil Nadu India 600006
    43 Christian Medical College Hospital Vellore Vellore Tamil Nadu India 632004
    44 Nizam's Institute of Medical Sciences (NIMS) Hyderabad Telangana India 500082
    45 Apollo Gleneagles Hospital Kolkata West Bengal India 700054
    46 Postgraduate Institute of Medical Education and Research Chandigarh India 160012
    47 All India Institute of Medical Sciences New Delhi India 110029
    48 National Hospital Organization Higashisaitama National Hospital Hasuda-city Japan
    49 National Center of Neurology and Psychiatry Kodaira Japan
    50 Kumamoto University Hospital Kumamoto-shi Japan
    51 Kyoto University Hospital Kyoto Japan
    52 Nagoya City University Hospital Nagoya-shi Japan
    53 Hyogo College of Medicine Hospital Nishinomiya Japan
    54 Miyagi Children's Hospital Sendai Japan
    55 National Hospital Organization Toneyama National Hospital Toyonaka-shi Japan
    56 Tottori University Hospital Yonago Japan
    57 Pusan National University Yangsan Hospital Yangsan Gyeongsangnamdo Korea, Republic of 50612
    58 Samsung Medical Center Seoul Korea, Republic of 06351
    59 Seoul National University Hospital Seoul Korea, Republic of 3080
    60 Hospital Tunku Azizah Kuala Lumpur Kuala Lumpur Malaysia 50586
    61 University Malaya Medical Centre (UMMC) Pantai Malaysia 59100
    62 Hospital Angeles Chihuahua Chihuahua Mexico 31217
    63 Instituto Nacional de Pediatría Ciudad de mexico Mexico 04530
    64 Instituto Nacional de Rehabilitacion Tlalpan Mexico 14389
    65 Samodzielny Publiczny Centralny Szpital Kliniczny w Warszawie Warszawa Poland 02-097
    66 University of Puerto Rico - School of Medicine San Juan Puerto Rico 00936-5067
    67 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 125412
    68 "Saint Petersburg State Paediatric Medical University" based at Consultative and Diagnostic Centre Saint Petersburg Russian Federation 194100
    69 Kaohsiung Medical University Chung-Ho Memorial Hospital Kaohsiung Taiwan 80756
    70 National Taiwan University Hospital Taipei Taiwan 10002
    71 Siriraj Hospital Bangkok Thailand 10700
    72 Istanbul University- Instanbul Medical Faculty Istanbul Turkey 34093

    Sponsors and Collaborators

    • PTC Therapeutics

    Investigators

    • Study Director: Vinay Penematsa, MD, PTC Therapeutics, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    PTC Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03179631
    Other Study ID Numbers:
    • PTC124-GD-041-DMD
    First Posted:
    Jun 7, 2017
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    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
    Dystrophinopathy
    Nonsense Mutation
    Premature Stop Codon
    Becker Muscular Dystrophy
    DMD/BMD
    PTC124
    Ataluren
    Additional relevant MeSH terms:
    Muscular Dystrophies
    Muscular Dystrophy, Duchenne
    Musculoskeletal Diseases
    Muscular Diseases
    Muscular Disorders, Atrophic
    Nervous System Diseases
    Neuromuscular Diseases
    Genetic Diseases, Inborn
    Genetic Diseases, X-Linked

    Study Results

    No Results Posted as of Mar 31, 2022