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Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy (ACT DMD)

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. Read our disclaimer for details. Identifier: NCT01826487
Recruitment Status : Completed
First Posted : April 8, 2013
Last Update Posted : April 8, 2019
Information provided by (Responsible Party):
PTC Therapeutics

Brief Summary:
Dystrophinopathy is a disease continuum that includes Duchenne muscular dystrophy, which develops in boys. It is caused by a mutation in the gene for dystrophin, a protein that is important for maintaining normal muscle structure and function. Loss of dystrophin causes muscle fragility that leads to weakness and loss of walking ability. A specific type of mutation, called a nonsense (premature stop codon) mutation is the cause of dystrophinopathy in approximately 10-15% of boys with the disease. Ataluren is an orally delivered, investigational drug that has the potential to overcome the effects of the nonsense mutation. The main goal of this Phase 3 study is to evaluate the effect of ataluren on walking ability. The effect of ataluren on physical function, quality of life, and activities of daily living will be evaluated. This study will also provide additional information on the long-term safety of ataluren.

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

Detailed Description:
This study is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of ataluren 10, 10, 20 mg/kg in patients with nonsense-mutation (nm) dystrophinopathy. Patients will be randomized in a 1:1 ratio to ataluren 10-, 10-, 20-mg/kg dose level or placebo. Patients will receive study drug TID at morning, midday, and evening. It is planned that 220 patients will be enrolled and patients will undergo 48 weeks of blinded treatment prior to the final analysis. Study assessments will be performed at clinic visits every 8 weeks. It is anticipated that an open-label extension study will be available to patients (who successfully complete the double-blind study) in countries where ataluren is not commercially available.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy
Study Start Date : March 2013
Actual Primary Completion Date : August 2015
Actual Study Completion Date : August 2015

Arm Intervention/treatment
Active Comparator: Ataluren
10, 10, 20 mg/kg
Drug: Ataluren
Ataluren PO 10-,10-,20-mg/kg for 48 weeks.
Other Name: PTC124

Placebo Comparator: Placebo
Matching placebo
Drug: Placebo
Placebo PO 10-,10-,20-,mg/kg for 48 weeks.

Primary Outcome Measures :
  1. Changes in the distance walked during a 6-minute walk test [ Time Frame: Baseline and 48 weeks ]

Secondary Outcome Measures :
  1. Physical function [ Time Frame: Baseline and 48 weeks ]
    North Star Ambulatory Assessment and Timed Function Testing

  2. Patient and/or parent-reported activities of daily living and disease symptoms [ Time Frame: Baseline and 48 weeks ]
  3. Quality of Life [ Time Frame: Baseline and 48 weeks ]
  4. Safety [ Time Frame: Baseline and 48 weeks ]
    Safety profile characterized by type, frequency, severity, timing, and relationship to study drug of any adverse events, or of abnormalities of laboratory tests, vital signs, physical examinations, or ECGs

  5. Ataluren blood levels [ Time Frame: Baseline and 48 weeks ]
  6. Compliance [ Time Frame: Baseline and 48 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years to 16 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Ability to provide written informed consent (parental/guardian consent if applicable)/assent per local requirements.
  • Male sex.
  • Age ≥7 and ≤16 years.
  • Phenotypic evidence of dystrophinopathy based on the onset of characteristic clinical symptoms or signs (eg. proximal muscle weakness, waddling gait, and Gowers' maneuver) by 6 years of age, an elevated serum creatinine kinase level, and ongoing difficulty with walking.
  • Documentation of the presence of a nonsense point mutation in the dystrophin gene as determined by gene sequencing from a laboratory certified by the College of American Pathologists (CAP), the Clinical Laboratory Improvement Act/Amendment (CLIA) or an equivalent organization.
  • Documentation that a blood sample has been drawn for confirmation of the presence of a nonsense mutation in the dystrophin gene.
  • Use of systemic corticosteroids (prednisone, prednisolone, or deflazacort) for a minimum of 6 months immediately prior to start of study treatment, with no significant change in dosage or dosing regimen (not related to body weight change) for a minimum of 3 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
  • Ability to walk ≥150 meters unassisted during the screening 6-minute walk test. Patients need to be below the protocol-specified threshold for %-predicted 6MWD.
  • Results of the 2 Baseline 6MWD results must be determined as valid and results of the Day 2 Baseline 6MWD must be within 20% of the Day 1 Baseline 6MWD.
  • Baseline 6MWD (mean of valid Day 1 and Day 2 values) must be no more than a 20% reduction from the valid Screening 6MWD.
  • Confirmed screening laboratory values within the central laboratory ranges (hepatic, renal, and serum electrolyte parameters)
  • Willingness to abstain from sexual intercourse or employ an approved method of contraception during the period of study drug administration and 6-week follow-up period.
  • Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, laboratory tests, and study restrictions.

Exclusion Criteria:

  • Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of study treatment.
  • Initiation of systemic corticosteroids therapy within 6 months prior to start of study treatment.
  • Change in systemic corticosteroid therapy (eg, change in type of drug, dose modification not related to body weight change, schedule modification, interruption, or reinitiation) within 3 months prior to start of study treatment.
  • Any change (initiation, change in type of drug, dose modification, schedule modification,interruption, discontinuation, or reinitiation) in prophylaxis/treatment for congestive heart failure (CHF) within 3 months prior to start of study treatment.
  • Ongoing use of coumarin-based anticoagulants (eg. warfarin), phenytoin, tolbutamide, or paclitaxel.
  • Prior therapy with ataluren.
  • Known hypersensitivity to any of the ingredients or excipients of the study drug
  • Exposure to another investigational drug within 3 months prior to start of study treatment.
  • History of major surgical procedure within 6 weeks prior to start of study treatment.
  • Ongoing immunosuppressive therapy (other than corticosteroids).
  • Ongoing participation in any clinical trial (except for studies specifically approved by PTC Therapeutics).
  • Expectation of major surgical procedure (eg, scoliosis surgery) during the 12-month treatment period of the study.
  • Requirement for daytime ventilator assistance. Note: Evening ventilator assistance and use of bi-level positive airway pressure (Bi-PAP) therapy is allowed.
  • Uncontrolled clinical symptoms and signs of CHF (American College of Cardiology/American Heart Association Stage C or Stage D).
  • Prior or ongoing medical condition (eg, concomitant illness, psychiatric condition, behavioral disorder, alcoholism, drug abuse), medical history, physical findings (eg. lower limb injury that may affect 6MWT performance), ECG findings, or laboratory abnormality that, in the investigator's opinion, could adversely affect the safety of the subject, makes it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results.

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): NCT01826487

  Hide Study Locations
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United States, California
University of California, Los Angeles
Los Angeles, California, United States, 90095
UC Davis Medical Center
Sacramento, California, United States, 95817
United States, Colorado
Children's Hospital Colorado - Center for Cancer and Blood Disorders
Aurora, Colorado, United States, 80045
United States, Florida
Child Neurology Center of Northwest Florida
Gulf Breeze, Florida, United States, 32561
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research
Saint Louis, Missouri, United States, 63110
United States, New York
Columbia University College of Physicians & Surgeons
New York, New York, United States, 10032
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229-3039
Nationwide Children's Hospital
Columbus, Ohio, United States, 43209
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Childrens Medical Center Dallas, Texas
Dallas, Texas, United States, 75207
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84112
United States, Washington
Seattle Children's Hospital - Childhood Cancer and Blood Disorders
Seattle, Washington, United States, 98105
Australia, New South Wales
The Children's Hospital at Westmead
Westmead, New South Wales, Australia, 2145
Australia, Victoria
The Royal Children's Hospital
Parkville, Victoria, Australia, 3052
UZ Leuven
Leuven, Belgium, 3000
Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira
Rio de Janeiro, Brazil, 21.941-912
Sao Paulo University -HC/FMUSP
São Paulo, Brazil, 05403-900
Canada, Alberta
Alberta Children's Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, British Columbia
British Columbia Children's Hospital
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Children's Hospital of Western Ontario
London, Ontario, Canada, N6A 2E3
Hospital Luis Calvo Mackenna
Santiago, Región Metropolitana, Chile
Hospital Clinico Universidad Catolica
Santiago, Chile, 8330073
University Hospital Brno
Brno, Czechia, 635 00
Motol University Hospital
Praha, Czechia, 150 06
Hospital de la Timone
Marseille, France, 13385
CHU de Nantes
Nantes Cedex, France, 44093
Hopital Necker - Enfants Malades
Paris, France, 75015
Groupe Hospitalier La Pitie-Salpetriere
Paris, France, 75651
University of Essen-Duisburg
Essen, Germany, 45122
University Hospital Medical Center Freiburg
Freiburg, Germany, 79106
Hadassah University Hospital
Jerusalem, Israel, 91240
Policlinico Universitario G. Martino
Messina, Sicily, Italy, 98125
Fondazione IRCS Ca Granda Ospedale Maggiore Policlinico di Milano
Milan, Italy, 20122
Bambino Gesu Hospital
Rome, Italy, 00165
U.O. Complessa di Neuropsichiatria Infantile
Rome, Italy, 00168
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 110-744
Medical University of Warsaw
Warsaw, Poland, 85- 822
Hospital Sant Joan de Deu
Barcelona, Spain, 08950
Hospital Universitari i Politecnic la Fe
Valencia, Spain, 46026
Queen Silvia Children's Hospital
Goteburg, Sweden, SE-416 85
Astrid Lindgren Childrens Hospital
Stockholm, Sweden, 17176
CHUV Lausanne
Lausanne, Switzerland, 1011
Hacettepe Childrens Hospital
Ankara, Turkey, 06100
United Kingdom
University College London Institute of Child Health
London, United Kingdom, WC1N 1EH
Royal Manchester Children's Hospital
Manchester, United Kingdom, M13 9WL
The Newcastle upon Tyne Hospitals, NHS Foundation Trust
Newcastle upon Tyne, United Kingdom, NE1 3BZ
Sponsors and Collaborators
PTC Therapeutics
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Study Director: Robert Spiegel, M.D. PTC Therapeutics

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: PTC Therapeutics Identifier: NCT01826487     History of Changes
Other Study ID Numbers: PTC124-GD-020-DMD
First Posted: April 8, 2013    Key Record Dates
Last Update Posted: April 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by PTC Therapeutics:
Duchenne muscular dystrophy
Nonsense mutation
Premature stop codon
Becker muscular dystrophy

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