Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)

• Change in 6 Minute Walk Test (6MWT) from Baseline [ Time Frame: Baseline to Week 96 ]
  

• Dystrophin protein expression [ Time Frame: Baseline to Week 48 ]
  
• Ability to rise independently from the floor [ Time Frame: Baseline to Week 96 ]
  
• Functional status as measured by loss of ambulation (LOA) from Baseline [ Time Frame: Baseline to Week 96 ]
  
• North Star Ambulatory Assessment (NSAA) from Baseline [ Time Frame: Baseline to Week 96 ]
  
• Forced vital capacity (FVC)% predicted from Baseline [ Time Frame: Baseline to Week 96 ]
  
• Frequency of falls from Baseline [ Time Frame: Baseline to Week 96 ]
  
• Left ventricular ejection fraction (LVEF) from baseline [ Time Frame: Baseline to Week 96 ]
  

This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible patients with out-of-frame deletion mutations amenable to exon 45 or 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 30 mg/kg SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group, 66 patients) or placebo (33 patients) for up to 96 weeks (the placebo-controlled period of the trial). This will be followed by an open label extension period in which all patients will receive open-label active treatment for up to 96 weeks.

The study will enroll approximately 99 patients, with a planned minimum target of 45 patients amenable to exon 45 skipping and 45 patients amenable to exon 53 skipping.

Approximately 66 patients will be randomized to receive active treatment with either SRP-4045 or SRP-4053 (depending on deletion mutation), and 33 patients will be randomized to receive placebo. Twice as many patients will receive active treatment as will receive placebo (2:1 randomization).

When approximately 75 patients have been in the trial for 48 weeks a group of independent experts will review key study results and will make a determination on whether patients will roll into the open-label period of the study and receive active drug or continue in the placebo-controlled period out to Week 96 as planned.

Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests such as the six-minute walk test (6MWT). All patients will undergo a muscle biopsy at baseline and a second muscle biopsy at Week 48.

Safety will be assessed through the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study.

Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of both drugs.