Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy (FORWARD-53)

Prior treatment

• Part B and Part C: Major surgery within 3 months prior to Day 1 or planned major surgery for any time during the study.
• Part B: Diagnosis of active alcohol, cannabinoid, or other substance use disorder (except nicotine) within 6 months prior to the Screening visit
• Part C: Any recreational substance use (including prescribed cannabinoids), with the exception of nicotine, irrespective of legality, within 2 months prior to Screening and/or unwilling to refrain from such use for the duration of the study.

Other

• Clinically significant medical finding on the physical examination other than DMD that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the study procedures.

• Part A and Part B:
• Part A patients may be screened for Part B upon completion of a washout period of ≥18 weeks from last dose in Part A. New patients may also be screened for Part B
• Diagnosis of DMD based on clinical phenotype.
• Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
• Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) (Part B ).
• Ambulatory or non-ambulatory male
• Stable pulmonary and cardiac function, as measured by the following: (Part B):
  • 1\. Reproducible percent predicted forced vital capacity (FVC) ≥50%; 2. Left ventricular ejection fraction (LVEF) \>55% in patients \<10 years of age and \>45% in patients ≥10 years of age, as measured (and documented) by echocardiogram (ECHO) and/or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.
  • 7.Adequate muscle at Screening to perform open muscle biopsies, preferably deltoid.
  • 8\. Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy that occurred ≥6 months prior to Screening and no changes in dose ≤3 months prior to Screening visit (Part B ).
  • Part C
• New patients to be screened for Part C.
• Diagnosis of DMD based on clinical phenotype.
• Documented mutation in the DMD gene associated with DMD that is amenable to exon 53 intervention
• Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) .
• Ambulatory male
• Stable pulmonary and cardiac function, as measured by the following:
  • 1\. Reproducible percent predicted forced vital capacity (FVC) ≥50%; 2. Left ventricular ejection fraction (LVEF) \>55% in patients as measured (and documented) by echocardiogram (ECHO) and/or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.
  • 7\. Adequate muscle at Screening to perform open muscle biopsies, preferably deltoid.
  • 8\. Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy that occurred ≥6 months prior to Screening and no changes in dose ≤3 months prior to Screening visit .