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.
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. For this portion of the study, up to 15 new patients will be enrolled into Part C of the study. All patients will undergo an open muscle biopsy, at baseline and following 24 weeks of treatment. The primary endpoint for Part B is the measurement of dystrophin protein levels. Participants will also be evaluated for safety, tolerability, digital and functional endpoints. 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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
WVE-N531 is an antisense oligonucleotide (ASO)
Arkansas Children's Hospital
Little Rock, Arkansas, United States
RECRUITINGRare Disease Research LLC
Atlanta, Georgia, United States
RECRUITINGIstiklal Hospital/ Clinical Research Unit
Amman, Jordan
RECRUITINGThe Specialty Hospital (TSH)/ Advanced Clinical Center
Amman, Jordan
RECRUITINGOxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust
Headington, Oxford, United Kingdom
RECRUITINGPart A: Safety: Proportion of patients with adverse events (AEs)
Time frame: Day 1 (initial dose) up to 24 weeks after the last dose of Part A
Part B: Pharmacodynamics: Dystrophin level (% normal dystrophin) as assessed by Western blot of muscle tissue following multiple doses of WVE-N531
Time frame: At Week 26 and at Week 50 of Part B
Part C: Pharmacodynamics: Change from baseline dystrophin level (% normal dystrophin) as assessed by a validated assay analysis in muscle tissue following multiple doses of WVE-N531
Time frame: At Baseline and following 24 weeks of treatment in Part C
Part A: Pharmacokinetics: Concentration of WVE-N531 in muscle tissue
Time frame: Day 1 (initial dose) through 2 weeks after the last dose of Part A
Part A: Pharmacodynamics: Dystrophin level (% normal dystrophin) as assessed by Western blot of muscle tissue following multiple doses of WVE-N531
Time frame: Day 1 (initial dose) through 2 weeks after the last dose of Part A
Part B: North Star Ambulatory Assessment (NSAA) (Version 2.0), including time to stand and a timed 10-meter walk/run, with a range of 0 to 34 where higher scores indicate better outcome.
Time frame: Collected at baseline, Weeks 24 and 48 of Part B, at baseline and Weeks 26 and 50 of the Extension Arm
Part B: Performance of the Upper Limb (PUL) (Version 2.0) with a range of 0 to 64 where higher scores indicate a better outcome.
Time frame: Collected at baseline, Weeks 24 and 48 of Part B, at baseline and Weeks 26 and 50 of the Extension Arm
Part B: Stride Velocity 95th Centile (SV95C)/upper limb outcome (non-ambulatory patients)
Time frame: Collected at baseline, Weeks 24 and 48 of Part B, at baseline and Weeks 26 and 50 of the Extension Arm
Part C: North Star Ambulatory Assessment (NSAA) (Version 2.0), including time to stand and a timed 10-meter walk/run, with a range of 0 to 34 where higher scores indicate better outcome.
Time frame: Collected at baseline and Week 24 of Part C
Part C: Performance of the Upper Limb (PUL) (Version 2.0) with a range of 0 to 64 where higher scores indicate a better outcome.
Time frame: Collected at baseline and Week 24 of Part C
Part C: Stride Velocity 95th Centile (SV95C)/upper limb outcome (non-ambulatory patients)
Time frame: Collected at baseline and Week 24 of Part C
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