Phase 2B Study of PTC124 (Ataluren) in Duchenne/Becker Muscular Dystrophy (DMD/BMD)
Condition: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Intervention: Ataluren; Placebo
Intervention description: Ataluren will be administered as per the dose and schedule specified in the respective arms.; Placebo matching to ataluren will be administered as the schedule specified in the respective arm.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 174.0
Sex: Male
Minimum age: 5 Years
Healthy volunteers: No
Keywords: Duchenne muscular dystrophy; Becker muscular dystrophy; Nonsense mutation; Premature stop codon; DMD/BMD; PTC124

Summary:

      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 13 percent
      (%) 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 2b
      trial that will evaluate the clinical benefit of ataluren in boys with DMD/BMD due to a
      nonsense mutation. The main goals of the study are to understand whether ataluren can improve
      walking, activity, muscle function, and strength and whether the drug can safely be given for
      a long period of time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ability to provide written informed consent (parental/guardian consent if
             applicable)/assent (if <18 years of age).

          -  Male sex.

          -  Age ≥5 years.

          -  Phenotypic evidence of DMD/BMD based on the onset of characteristic clinical symptoms
             or signs (that is, proximal muscle weakness, waddling gait, and Gowers' maneuver) by 9
             years of age, an elevated serum CK level, and ongoing difficulty with ambulation.

          -  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.

          -  Ability to walk ≥75 meters unassisted during the screening 6-minute walk test. Note:
             Other personal assistance or use of assistive devices for ambulation (for example,
             short leg braces, long leg braces or walkers) were not permitted.

          -  Confirmed screening laboratory values within the central laboratory ranges (hepatic,
             adrenal, renal, and serum electrolytes parameters).

          -  In participants who were sexually active, willingness to abstain from sexual
             intercourse or employ a barrier or medical method of contraception during the study
             drug administration and 6-week follow-up periods.

          -  Willingness and ability to comply with scheduled visits, drug administration plan,
             study procedures, laboratory tests, and study restrictions. Note: Psychological,
             social, familial, or geographical factors that might preclude adequate study
             participation (in particular, the ability to satisfactorily perform the 6MWT) should
             have been considered.

        Exclusion Criteria:

          -  Treatment with systemic aminoglycoside antibiotics within 3 months prior to start of
             study treatment.

          -  Initiation of systemic corticosteroid therapy within 6 months prior to start of study
             treatment or change in systemic corticosteroid therapy (for example, initiation,
             change in type of drug, dose modification not related to body weight change, schedule
             modification, interruption, discontinuation, 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 within 3 months prior to start of study treatment.

          -  Treatment with warfarin within 1 month prior to start of study treatment.

          -  Prior therapy with ataluren.

          -  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 30 days prior to start of study treatment.

          -  Ongoing immunosuppressive therapy (other than corticosteroids).

          -  Ongoing participation in any other therapeutic clinical trial.

          -  Expectation of major surgical procedure (for example, scoliosis surgery) during the
             12-month treatment period of the study.

          -  Requirement for daytime ventilator assistance.

          -  Clinical symptoms and signs of congestive heart failure (American College of
             Cardiology/American Heart Association Stage C or Stage D) or evidence on
             echocardiogram of clinically significant myopathy.

          -  Prior or ongoing medical condition (for example, 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 participant, makes it
             unlikely that the course of treatment or follow-up would be completed, or could impair
             the assessment of study results.