= Fully recruited
= Recruiting
= Not yet recruiting
= Enrolling by invitation
This is a Phase 1b/2 open label study to evaluate the safety, tolerability, pharmacokinetic (how the drug is absorbed and metabolised in the body), pharmacodynamic (how the drug affects the body), and clinical effects of intravenous (IV) WVE-N531, an exon skipping investigational therapy, 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 and Part B are 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.
Following completion of Part A, eligible patients rolled over into Part B to continue to receive treatment. In addition, new patients were enrolled up to a total of 11 patients in Part B. All patients received WVE-N531 at 10 mg/kg every other week (Q2W) until competent authority approval of a protocol update, when all patients were switched to Q4W dosing. Muscle biopsies were performed following 24 weeks and for new Part B patients (those that did not take part in Part A) following 48 weeks of treatment. Following completion of Part B, all patients elected to continue to receive study drug at Q4W for up to 1 year in an optional Part B Extension Arm.
The primary endpoint for Part B was the measurement of dystrophin protein levels. Participants will also be evaluated for safety, tolerability, digital and functional endpoints.
In Part C, up to 15 new patients will be enrolled. All patients will undergo an open muscle biopsy, at baseline and following 24 weeks of treatment.
The primary endpoint for Part C is the measurement of dystrophin protein levels. Participants will also be evaluated for safety, tolerability, digital and functional endpoints. Safety monitoring will occur through 10 months after the last dose.
This is an open-label study, meaning all participants and investigators will know that the drug is being administered. This clinical trial is not placebo-controlled, meaning there will be no dummy treatment.
Part A and Part B:
4. Score of ≥1 on item 1 or 2 of the shoulder component of the Performance of the Upper Limb (PUL) (Part B ).
5. Ambulatory or non-ambulatory male
6. 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
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 .