Phase 2b Study of PTC124 in Duchenne/Becker Muscular Dystrophy (DMD/BMD)

This study is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled,
dose-ranging, efficacy and safety study, designed to document the clinical benefit of PTC124
when administered as therapy of patients with DMD/BMD due to a nonsense mutation (premature
stop codon) in the dystrophin gene. It is planned that ~165 boys who are at least 5 years of
age and can walk at least 75 meters (80 yards) will be enrolled. Study subjects will be
enrolled at sites in North America, Europe, Israel, and Australia. They will be randomized in
a 1:1:1 ratio to either a higher dose of PTC124, a lower dose of PTC124, or placebo. Subjects
will receive study drug 3 times per day (at breakfast, lunch, and dinner) for 48 weeks.
Subjects will be evaluated at clinic visits every 6 weeks. 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 of the study. At the
completion of blinded treatment, all compliant participants will be eligible to receive
open-label PTC124 in a separate extension study.

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 (ie., proximal muscle weakness, waddling gait, and Gowers' maneuver) by 9
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.

- Ability to walk ≥75 meters unassisted during the screening 6-minute walk test.

- Documentation that a baseline renal ultrasound has been performed.

- Confirmed screening laboratory values within the central laboratory ranges (adrenal,
renal, and serum electrolytes parameters)

- 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 corticosteroid therapy within 6 months prior to start of study
treatment or change in systemic corticosteroid therapy (eg, 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 PTC124.

- 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 (eg, 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 (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.