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Phase 2a Extension Study of Ataluren (PTC124) in Duchenne Muscular Dystrophy (DMD)

key information

study id #: NCT00759876

condition: Duchenne Muscular Dystrophy

status: terminated


Duchenne muscular dystrophy (DMD) is a genetic disorder that 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 during childhood and teenage years. A specific type of mutation, called a nonsense (premature stop codon) mutation, is the cause of DMD 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. This study is a Phase 2a extension trial that will evaluate the long-term safety of ataluren in boys with nonsense mutation DMD, as determined by adverse events and laboratory abnormalities. The study will also assess changes in walking, muscle function, strength, and other important clinical and laboratory measures.

intervention: Ataluren

mechanism of action: Stop codon read through to promote dystrophin production

results: https://clinicaltrials.gov/ct2/show/results/NCT00759876

last updated: April 27, 2019

study details

start date: July 31, 2008

estimated completion: May 31, 2010

phase of development: Phase 2

size / enrollment: 36

study description:
This Phase 2a, multicenter, open-label safety and efficacy study will be performed at 3 sites in the United States. The study will enroll up to 38 subjects with nonsense mutation Duchenne muscular dystrophy who participated in a previous Phase 2a study of ataluren (Protocol Number PTC124-GD-004-DMD). Subjects will receive study drug 3 times per day (at breakfast, lunch, and dinner) for approximately 96 weeks (approximately 2 years). Study assessments will be performed at clinic visits during screening, every 6 weeks for the first 24 weeks, and then every 12 weeks until the end of the study.
Additional safety laboratory testing, which may be performed at the investigational site or at an accredited local laboratory or clinic, is required every 3 weeks for the first 24 weeks and then every 6 weeks from Week 24 to Week 48. Subjects will have a biceps muscle biopsy before ataluren treatment and again after 24 weeks of ataluren treatment to evaluate changes in muscle dystrophin expression.
An evaluation of the effects of ataluren on corticosteroid pharmacokinetics will be performed. Associated with this ataluren clinical trial is a substudy that will use magnetic resonance evaluations to assess changes in the composition of muscles of the legs.

primary outcomes:

  • Long-term safety [ Time Frame:2 years ]

secondary outcomes:

  • Ambulation [Time Frame: 2 years]
  • Proximal muscle function [Time Frame: 2 years]
  • Heart rate [Time Frame: 2 years]
  • Cognitive ability [Time Frame: 2 years]
  • Quality of life [Time Frame: 2 years]
  • Activities of daily living [Time Frame: 2 years]
  • Muscle fragility [Time Frame: 2 years]
  • Biceps muscle dystrophin expression [Time Frame: 2 years]
  • Compliance with PTC124 treatment [Time Frame: 2 years]
  • PTC124 pharmacokinetics [Time Frame: 2 years]
  • PTC124 effect on corticosteroid pharmacokinetics [Time Frame: 2 years]
  • Muscle composition as assessed by magnetic resonance [Time Frame: 2 years]

inclusion criteria:
• Completion of ataluren treatment in the previous Phase 2a study protocol (Protocol PTC124-GD-004-DMD).
• Ability to provide written informed consent (parental/guardian consent if applicable)/assent (if <18 years of age).
• Confirmed screening laboratory values within the central laboratory ranges.
• In subjects who are sexually active, willingness to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and the 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.
• Treatment with warfarin within 1 month prior to start of study treatment.
• Known hypersensitivity to any of the ingredients or excipients of the study drug (Litesse® UltraTM [refined polydextrose], polyethylene glycol 3350, Lutrol® micro F127 [poloxamer 407], mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, Cab-O-Sil® M5P [colloidal silica], magnesium stearate).
• Exposure to another investigational drug within 2 months prior to start of study treatment.
• History of major surgical procedure within 1 month prior to start of study treatment.
• Ongoing immunosuppressive therapy (other than corticosteroids).
• Ongoing participation in any other clinical trial (except for substudies specifically approved by PTC Therapeutics).
• Clinically significant symptoms and signs of congestive heart failure (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, electrocardiogram 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.

study contacts

sponsor: PTC Therapeutics

investigators: Leone Atkinson

locations: United States