Trial record 1 of 1 for:    NCT01826487
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Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy (ACT DMD)

This study is currently recruiting participants.
Verified April 2014 by PTC Therapeutics
Sponsor:
Information provided by (Responsible Party):
PTC Therapeutics
ClinicalTrials.gov Identifier:
NCT01826487
First received: March 26, 2013
Last updated: April 15, 2014
Last verified: April 2014

March 26, 2013
April 15, 2014
March 2013
June 2015   (final data collection date for primary outcome measure)
Changes in the distance walked during a 6-minute walk test [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
To determine the effect of ataluren on ambulation in patients with nonsense mutation DMD (as assessed by changes in the distance walked during a 6-minute walk test) [ Time Frame: Baseline and 48 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01826487 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy
A Phase 3 Efficacy and Safety Study of Ataluren (PTC124) in Patients With Nonsense Mutation Dystrophinopathy

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • 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
    Other Name: PTC124
  • Drug: Placebo
  • Active Comparator: Ataluren
    10, 10, 20 mg/kg
    Intervention: Drug: Ataluren
  • Placebo Comparator: Placebo
    Matching placebo
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
220
Not Provided
June 2015   (final data collection date for primary outcome measure)

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.
Male
7 Years to 16 Years
No
Contact: Diane Goetz 908-912-9256 dgoetz@ptcbio.com
Contact: Diane Goetz 866-282-5873 patientinfo@ptcbio.com
United States,   Australia,   Belgium,   Brazil,   Canada,   Chile,   Czech Republic,   France,   Germany,   Israel,   Italy,   Korea, Republic of,   Poland,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom
 
NCT01826487
PTC124-GD-020-DMD
Yes
PTC Therapeutics
PTC Therapeutics
Not Provided
Study Director: Robert Spiegel, M.D. PTC Therapeutics
PTC Therapeutics
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP