Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada
Condition: Duchenne Muscular Dystrophy; Becker Muscular Dystrophy; Dystrophinopathy
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Intervention: Ataluren
Intervention description: Oral powder for suspension
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 94.0
Sex: Male
Healthy volunteers: No
Keywords: Duchenne muscular dystrophy; Becker muscular dystrophy; Nonsense mutation; Premature stop codon; DMD; BMD; nmDBMD; DBMD; Ataluren; PTC124

Summary:

      Duchenne/Becker muscular dystrophy (DBMD) 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 DBMD 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 comprises a Phase 3, open-label study of ataluren in participants with nmDBMD who
      previously received ataluren at an Investigator site in a prior PTC-sponsored clinical study.
      A separate open-label study (PTC124-GD-016-DMD; NCT01247207) is being conducted for nmDBMD
      participants who previously received ataluren at an Investigator site in the United States
      (US).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Evidence of signed and dated informed consent/assent document(s) indicating that the
             participant (and/or his parent/legal guardian) has been informed of all pertinent
             aspects of the trial. Note: If the study candidate is considered a child under local
             regulation, a parent or legal guardian must provide written consent prior to
             initiation of study screening procedures and the study candidate may be required to
             provide written assent. The rules of the responsible Institutional Review
             Board/Independent Ethics Committee (IRB/IEC) regarding whether 1 or both parents must
             provide consent and the appropriate ages for obtaining consent and assent from the
             participant should be followed.

          2. History of exposure to ataluren in a prior PTC study in nmDBMD. Note: Participants are
             considered eligible only if they received ataluren during their participation in 1 or
             more prior PTC-sponsored studies of ataluren in nmDBMD. Note: Participants who have
             participated in a prior or ongoing PTC study with ataluren in nmDBMD at a trial site
             in the US or Canada, but reside outside of the US and Canada, may be eligible for this
             study (with the approval of the PTC Therapeutics Medical Monitor).

          3. Male sex.

          4. In participants 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.

          5. 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 should be considered.

        Exclusion Criteria:

          1. Exposure to another investigational drug within 1 month prior to start of study
             treatment.

          2. Eligibility for another ataluren clinical trial that is actively enrolling study
             participants.

          3. 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).

          4. Ongoing use of the following medications:

               1. Coumarin-based anticoagulants (for example, warfarin), phenytoin, tolbutamide, or
                  paclitaxel.

               2. Systemic aminoglycoside therapy

          5. Ongoing uncontrolled medical/surgical condition, electrocardiogram (ECG) findings, or
             laboratory abnormality that, in the Investigator's opinion, could adversely affect the
             safety of the participant or make it unlikely that follow-up would be completed.