Trial record 1 of 1 for:    NCT01826487
Previous Study | Return to List | Next Study

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by PTC Therapeutics
Information provided by (Responsible Party):
PTC Therapeutics Identifier:
First received: March 26, 2013
Last updated: July 21, 2014
Last verified: July 2014

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy

Resource links provided by NLM:

Further study details as provided by PTC Therapeutics:

Primary Outcome Measures:
  • Changes in the distance walked during a 6-minute walk test [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Physical function [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
    North Star Ambulatory Assessment and Timed Function Testing

  • Patient and/or parent-reported activities of daily living and disease symptoms [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
  • Quality of Life [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: Yes ]
    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

  • Ataluren blood levels [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
  • Compliance [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
Study Start Date: March 2013
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ataluren
10, 10, 20 mg/kg
Drug: Ataluren
Other Name: PTC124
Placebo Comparator: Placebo
Matching placebo
Drug: Placebo

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.


Ages Eligible for Study:   7 Years to 16 Years
Genders 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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01826487

Contact: Diane Goetz 908-912-9256
Contact: Diane Goetz 866-282-5873

  Hide Study Locations
United States, California
University of California, Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Angel Hu    310-825-3264   
Principal Investigator: Perry Shieh, MD         
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Erica Goude, BA CCRP    916-734-0968   
Principal Investigator: Craig McDonald, MD         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305-5236
Contact: Shirley Paulose    650-724-3792   
Principal Investigator: John Day         
United States, Colorado
Children's Hospital Colorado - Center for Cancer and Blood Disorders Recruiting
Aurora, Colorado, United States, 80045
Contact: Melissa Gibbons    720-777-3697   
Principal Investigator: Julie Parsons         
United States, Florida
Child Neurology Center of Northwest Florida Recruiting
Gulf Breeze, Florida, United States, 32561
Contact: Lynn Head    850-934-1299   
Principal Investigator: Ben Renfroe, MD         
Miami Children's Hospital Recruiting
Miami, Florida, United States, 33155
Contact: Silvia Balladares-Huete         
Principal Investigator: Maria Franco, MD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Susan Rohde    312-942-0079   
Principal Investigator: Peter Heydemann, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Carrie Stephan    319-356-2673   
Principal Investigator: Katherine Mathews, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Gabrielle Rico    913-588-5703   
Principal Investigator: Richard Barohn, MD         
United States, Massachusetts
Children's Hospital Boston Recruiting
Boston, Massachusetts, United States, 02115
Contact: Nicole Visyak    857-218-4677   
Principal Investigator: Basil Darras, MD         
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Catherine Correia         
Principal Investigator: Gregory Sawicki, MD         
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Cameron Naughton    612-625-4882   
Principal Investigator: Peter Karachunski, MD         
United States, Missouri
Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Betsy Malkus    314-362-1624   
Principal Investigator: Anne Connolly, MD         
United States, New York
Columbia University College of Physicians & Surgeons Recruiting
New York, New York, United States, 10032
Contact: Jonathan Marra    212-305-2461   
Principal Investigator: Jacinda Sampson, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229-3039
Contact: Paula Morehart    513-636-8967   
Principal Investigator: Brenda Wong, MD         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43209
Contact: Susan Gailey    614-355-2897   
Principal Investigator: Kevin Flanigan, MD         
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Bryn McCarthy    503-418-8297   
Principal Investigator: Erika Finanger, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Nancy Videon    267-426-7163   
Principal Investigator: Gihan Tennekoon, MD         
Children's Hospital of Pittsburgh Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jennifer Monahan    412-692-5176   
Principal Investigator: Hoda Abdel-Hamid, MD         
United States, Texas
Childrens Medical Center Dallas, Texas Recruiting
Dallas, Texas, United States, 75207
Contact: Sharon Kern    214-456-8755   
Principal Investigator: Susan Iannaccone, MD         
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Gloria Orozco    832-822-1804   
Principal Investigator: Tim Lotze, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Missy Dixon    801-585-7606   
Principal Investigator: Russell Butterfield, MD         
United States, Washington
Seattle Children's Hospital - Childhood Cancer and Blood Disorders Recruiting
Seattle, Washington, United States, 98105
Contact: Ana Christensen    206-884-2756   
Principal Investigator: Susan Apkon, MD         
Australia, New South Wales
The Children's Hospital at Westmead Not yet recruiting
Westmead, New South Wales, Australia, 2145
Contact: Carleen Fernandez    61 2 9845 3004   
Principal Investigator: Kristi Jones, MD         
Australia, Victoria
The Royal Children's Hospital Recruiting
Parkville, Victoria, Australia, 3052
Contact: Daniella Villano    +61 (0)3 9345 4633   
Principal Investigator: Monique Ryan, MD         
UZ Leuven Recruiting
Leuven, Belgium, 3000
Contact: Corine Antonis    32 16 34 0250   
Principal Investigator: Nathalie Goemans, MD         
Universidade Federal do Rio de Janeiro - Instituto de Puericultura e Pediatria Martagao Gesteira Not yet recruiting
Rio de Janeiro, Brazil, 21.941-912
Sao Paulo University -HC/FMUSP Not yet recruiting
São Paulo, Brazil, 05403-900
Aleksandrovska Hospital University Not yet recruiting
Sofia, Bulgaria, 1431
Contact: Teodora Chamova    00359 889 802 252   
Principal Investigator: Velina Guergueltcheva-Bliznakova, MD         
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Jordan Turley    587-226-8108   
Principal Investigator: Jean Mah, MD         
Canada, British Columbia
British Columbia Children's Hospital Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Nela Martic    604-875-2345 ext 6549   
Principal Investigator: Katherine Selby, MD         
Canada, Ontario
Children's Hospital of Western Ontario Recruiting
London, Ontario, Canada, N6A 2E3
Contact: Sabeeh Alvi    519-619-2465   
Principal Investigator: Craig Campbell, MD         
Hospital Clinico Universidad Catolica Recruiting
Santiago, Chile, 8330073
Contact: Marcela Urzúa    569 93228312   
Principal Investigator: Raul Escobar, MD         
Hospital Luis Calvo Mackenna Recruiting
Santiago, Región Metropolitana, Chile
Contact: Carolina Wellmann    569 88853589   
Principal Investigator: Ricardo Erazo Torricelli, MD         
Czech Republic
University Hospital Brno Recruiting
Brno, Czech Republic, 635 00
Contact: Lenka Mrazova    +420 737 778 483   
Principal Investigator: Petr Vondracek, MD         
Motol University Hospital Recruiting
Praha, Czech Republic, 150 06
Contact: Marcela Hložánková    +42 022 4433360   
Principal Investigator: Martin Kudr, MD         
Hospital de la Timone Recruiting
Marseille, France, 13385
Contact: Marie-Elisabeth Fontaine    33 (0)4 91 38 46 44   
Principal Investigator: Brigitte Chabrol, MD         
CHU de Nantes Recruiting
Nantes Cedex, France, 44093
Contact: Raphaële Chasserieau    +33 2 40 08 78 80   
Principal Investigator: Yann Pereon, MD         
Hopital Necker - Enfants Malades Recruiting
Paris, France, 75015
Contact: Kim-Hanh Le Quan Sang    33 1 44 49 59 51   
Principal Investigator: Isabelle Desguerre, MD         
Groupe Hospitalier La Pitie-Salpetriere Recruiting
Paris, France, 75651
Contact: Oumar Diebate    01 42 16 66 49   
Principal Investigator: Thomas Voit, MD         
University of Essen-Duisburg Recruiting
Essen, Germany, 45122
Contact: Baerbel Leiendecker    49 201 / 723-2508   
Principal Investigator: Ulrike Schara, MD         
University Hospital Medical Center Freiburg Recruiting
Freiburg, Germany, 79106
Contact: Karin Schelb    049/761-270- 44740   
Principal Investigator: Janbernd Kirschner, MD         
University of Munich Not yet recruiting
Munich, Germany, 80337
Contact: Astrid Blascheck    49 (0)89 5160 5110   
Principal Investigator: Wolfgang Mueller-Felber, MD         
Hadassah University Hospital Recruiting
Jerusalem, Israel, 91240
Contact: Debbie Krojanker Yaffe    972-52-287-05-02   
Principal Investigator: Yoram Nevo, MD         
Fondazione IRCS Ca Granda Ospedale Maggiore Policlinico di Milano Recruiting
Milan, Italy, 20122
Contact: Francesca Magri    390255033807   
Principal Investigator: Giacomo Comi, MD         
U.O. Complessa di Neuropsichiatria Infantile Recruiting
Rome, Italy, 00168
Contact: Concetta Palermo    +39 0630 154 032   
Principal Investigator: Eugenio Mercuri, MD         
Bambino Gesu Hospital Recruiting
Rome, Italy, 00165
Contact: Giuseppe Pontrelli    +39 066859 3077   
Principal Investigator: Enrico Bertini, MD         
Policlinico Universitario G. Martino Not yet recruiting
Sicily, Italy, 98125
Contact: Sonia Messina    0039090 2217191   
Principal Investigator: Giuseppe Vita, MD         
Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Contact: Jisu Hong    82.2.2072.1652   
Principal Investigator: Jong-Hee Chae, MD         
Medical University of Warsaw Recruiting
Warsaw, Poland, 85- 822
Contact: Anna Kostera-Pruszczyk    48 606 393 921   
Principal Investigator: Anna Kaminska, MD         
Hospital Sant Joan de Deu Recruiting
Barcelona, Spain, 08950
Contact: Laura Sole Heuberger    +34 661 555 793   
Principal Investigator: Andres Nascimento, MD         
Hospital Universitari i Politecnic la Fe Recruiting
Valencia, Spain, 46026
Contact: M. Pilar Martí Martínez    +34 677 75 6564   
Principal Investigator: Jaun Vilchez Padilla, MD         
Queen Silvia Children's Hospital Recruiting
Goteburg, Sweden, SE-416 85
Contact: Anna-Lena Gustafsson    46-31-3436069   
Principal Investigator: Mar Tulinius, MD         
Astrid Lindgren Childrens Hospital Recruiting
Stockholm, Sweden, 17176
Contact: Monika Nordenbrand    46 8 517 77442   
Principal Investigator: Thomas Sejersen, MD         
CHUV Lausanne Recruiting
Lausanne, Switzerland, 1011
Contact: Sabina Rainy   
Principal Investigator: Pierre-Yves Jeannet, MD         
Hacettepe Childrens Hospital Recruiting
Ankara, Turkey, 06100
Contact: Merve Oruc    0505 303 88 39   
Principal Investigator: Haluk Topaloglu, MD         
Erciyes University Not yet recruiting
Kayseri, Turkey, 38039
Principal Investigator: Sefer Kumandas, MD         
United Kingdom
University College London Institute of Child Health Recruiting
London, United Kingdom, WC1N 1EH
Contact: Isabelle Wilson    0207 762 6892   
Principal Investigator: Francesco Muntoni, MD         
Royal Manchester Children's Hospital Not yet recruiting
Manchester, United Kingdom, M13 9WL
Contact: Laura Crowther    0161 701 6918   
Principal Investigator: Imelda Hughes, MD         
The Newcastle upon Tyne Hospitals, NHS Foundation Trust Recruiting
Newcastle upon Tyne, United Kingdom, NE1 3BZ
Contact: Becky Davis    0191 241 8649   
Principal Investigator: Michela Guglieri, MD         
Sponsors and Collaborators
PTC Therapeutics
Study Director: Robert Spiegel, M.D. PTC Therapeutics
  More Information

Additional Information:
No publications provided

Responsible Party: PTC Therapeutics Identifier: NCT01826487     History of Changes
Other Study ID Numbers: PTC124-GD-020-DMD
Study First Received: March 26, 2013
Last Updated: July 21, 2014
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Genetic Diseases, Inborn
Muscular Diseases
Muscular Dystrophies
Musculoskeletal Diseases
Nervous System Diseases
Neuromuscular Diseases
Muscular Disorders, Atrophic
Genetic Diseases, X-Linked
Pathological Conditions, Anatomical processed this record on August 01, 2014