Study of Ataluren (PTC124) in Nonambulatory Participants With Nonsense-Mutation-Mediated Duchenne/Becker Muscular Dystrophy (nmDMD/BMD)
Condition: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Intervention: Ataluren; Chronic Corticosteroid Therapy
Intervention description: Oral powder; Enrollment was stratified to ensure evaluation of approximately half of the participants were receiving chronic corticosteroid therapy and approximately half of participants were not receiving chronic corticosteroid therapy. Therefore, 3 out of 6 participants were receiving chronic corticosteriod therapy. For the participants receiving chronic corticosteriod therapy, a stable corticosteriod regimen was to be maintained during the study.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 7 Years
Healthy volunteers: No
Keywords: Duchenne muscular dystrophy; Becker muscular dystrophy; Nonsense mutation; Premature stop codon; DMD; BMD; Ataluren; PTC124

Summary:

      Duchenne/Becker muscular dystrophy (DMD/BMD) 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/BMD in approximately 10-15% of boys with the disease. Ataluren (PTC124) is an orally
      delivered, investigational drug that has the potential to overcome the effects of the
      nonsense mutation. This study is a Phase 2a trial that enrolled boys with nonsense mutation
      DMD/BMD who have lost independent mobility due to the disease. This study evaluated the
      safety and tolerability of ataluren (PTC124) and also evaluated efficacy outcomes in this
      participant population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of DMD or BMD

          -  Presence of a nonsense mutation in the dystrophin gene

          -  Unable to ambulate independently for ≥1 year due to DMD/BMD

          -  Presence of sufficient shoulder and elbow function to perform study-related functional
             procedures (for example, 9-hole peg test)

          -  Adequate hepatic, renal, and adrenal function

          -  Ability to provide evaluable pretreatment echocardiogram and lung function assessments

          -  Willingness and ability to comply with scheduled visits, drug administration plan,
             study procedures, laboratory tests, and study restrictions

          -  Ability to provide written informed consent (parental/guardian consent if
             applicable)/assent (if <18 years of age)

        Exclusion Criteria:

          -  Initiation of systemic corticosteroid therapy within 6 months prior to start of study
             treatment or use of systemic aminoglycoside antibiotic within 3 months prior to start
             of study treatment

          -  Use of any intermittent systemic corticosteroid therapy regimen (for example, 10 days
             on followed by 10 days off, weekend dosing, every-other-day dosing); note that
             participants must have either been receiving a daily dosing regimen of prednisone,
             prednisolone, or deflazacort at the time of enrollment into the study or must have not
             been receiving any systemic corticosteroids

          -  Any change in treatment for congestive heart failure within 3 months prior to start of
             study treatment

          -  Ongoing warfarin or phenytoin therapy

          -  Prior therapy with ataluren

          -  Known hypersensitivity to any of the ingredients or excipients of ataluren (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
             or expectation of major surgical procedure (for example, scoliosis surgery) during the
             48-week treatment period of the study

          -  Ongoing immunosuppressive therapy (other than corticosteroids)

          -  Ongoing participation in any other clinical trial

          -  Requirement for daytime ventilator assistance

          -  Uncontrolled clinical symptoms and signs of congestive heart failure

          -  Prior or ongoing medical condition (for example, concomitant illness, psychiatric
             condition, behavioral disorder, alcoholism, drug abuse), medical history, physical
             findings, electrocardiogram (ECG) findings, or laboratory abnormality that, in the
             investigator's opinion, could adversely affect the safety of the participant, makes it
             unlikely that the course of treatment or follow up would be completed, or could impair
             the assessment of study results