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A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy

Phase 3
7 Years
16 Years
Open (Enrolling)
Muscular Dystrophy, Duchenne, Muscular Dystrophies, Muscular Disorders, Atrophic, Muscular Diseases, Musculoskeletal Diseases, Neuromuscular Diseases, Nervous System Diseases, Genetic Diseases, X-Linked, Genetic Diseases, Inborn

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Trial Information

A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy

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.

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

- 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

- 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.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Outcome Measure:

Changes in the distance walked during a 6-minute walk test

Outcome Time Frame:

Baseline and 48 weeks

Safety Issue:


Principal Investigator

Jay Barth, M.D.

Investigator Role:

Study Director

Investigator Affiliation:

PTC Therapeutics


United States: Food and Drug Administration

Study ID:




Start Date:

March 2013

Completion Date:

Related Keywords:

  • Muscular Dystrophy, Duchenne
  • Muscular Dystrophies
  • Muscular Disorders, Atrophic
  • Muscular Diseases
  • Musculoskeletal Diseases
  • Neuromuscular Diseases
  • Nervous System Diseases
  • Genetic Diseases, X-Linked
  • Genetic Diseases, Inborn
  • Duchenne muscular dystrophy
  • Dystrophinopathy
  • Nonsense mutation
  • Premature stop codon
  • Becker muscular dystrophy
  • PTC124
  • Ataluren
  • Muscular Dystrophy, Duchenne
  • Genetic Diseases, Inborn
  • Muscular Diseases
  • Muscular Dystrophies
  • Musculoskeletal Diseases
  • Nervous System Diseases
  • Neuromuscular Diseases
  • Atrophy
  • Muscular Disorders, Atrophic
  • Genetic Diseases, X-Linked



University of Iowa Iowa City, Iowa  52242
Stanford University Medical Center Stanford, California  94305-5408
Rush University Medical Center Chicago, Illinois  60612-3824
University of Kansas Medical Center Kansas City, Kansas  66160-7353
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Nationwide Children's Hospital Columbus, Ohio  43205-2696
University of Minnesota Minneapolis, Minnesota  55455
University of Utah Salt Lake City, Utah  
Children's Hospital Boston Boston, Massachusetts  02115
Duke University Medical Center Durham, North Carolina  27710
Texas Children's Hospital Houston, Texas  
University of California, Los Angeles Los Angeles, California  
The Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
UC Davis Medical Center Sacramento, California  95817
Columbia University College of Physicians & Surgeons New York, New York  10032
Children's Hospital Colorado - Center for Cancer and Blood Disorders Aurora, Colorado  80045
Child Neurology Center of Northwest Florida Gulf Breeze, Florida  32561
Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research Saint Louis, Missouri  63110
Shriners Hospital for Children-Portland Portland, Oregon  97239
Childrens Medical Center Dallas, Texas Dallas, Texas  75207
Seattle Children's Hospital - Childhood Cancer and Blood Disorders Seattle, Washington  98105