An Open-label Phase 1b/2 Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy
This is a Phase 1b/2 open-label study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical effects of intravenous (IV) WVE-N531 in patients with Duchenne muscular dystrophy (DMD). To participate in the study, patients must have a documented mutation of the DMD gene that is amenable to exon 53 skipping intervention. This study has 3 parts, Part A, Part B, including Part B Extension Arm, and Part C. Part A is completed. Part B is completed. Following completion of Part B, all patients elected to continue to receive study drug in the optional Part B open-label Extension Arm. Part C has been added to the study and will enroll new patients.
‣ 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.
• 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 .