Back to resultsOpen-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy
Primary Purpose
Duchenne Muscular Dystrophy
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
WVE-N531
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase.
- 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).
Stable pulmonary and cardiac function, as measured by the following:
- Reproducible percent predicted forced vital capacity (FVC) ≥50%;
- 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) or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.
- Adequate deltoid muscle at Screening to perform open muscle biopsies.
- 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.
Exclusion Criteria:
Cardiac insufficiency:
- Severe cardiomyopathy that, in the opinion of the Investigator, prohibits participation in this study; however, cardiomyopathy that is managed by angiotensin-converting-enzyme (ACE) inhibitors or beta blockers is acceptable provided the participant meets the LVEF inclusion criterion.
- Any other evidence of clinically significant structural or functional heart abnormality.
- Need for daytime mechanical or noninvasive ventilation OR anticipated need for daytime mechanical or noninvasive ventilation within the next year in the opinion of the Investigator. Nighttime noninvasive ventilation is permitted.
- Received prior treatment with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) or drisapersen.
- Received prior treatment with gene therapy for DMD.
- Received treatment with ataluren, viltolarsen, eteplirsen, or golodirsen within the 14 weeks prior to Screening.
- Received any investigational drug within 3 months or 5 half-lives, whichever is longer prior to Screening.
Sites / Locations
- London Health Sciences Centre - HospitalRecruiting
- Oxford Children's Hospital, Oxford University Hospitals NHS Foundation TrustRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
WVE-N531
Arm Description
Outcomes
Primary Outcome Measures
Safety: Proportion of patients with adverse events (AEs)
Secondary Outcome Measures
Pharmacokinetics: Concentration of WVE-N531 in muscle tissue
Pharmacodynamics: Dystrophin level (% normal dystrophin) as assessed by Western blot of muscle tissue following multiple doses of WVE-N531
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04906460
Brief Title
Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy
Official Title
An Open-label Phase 1b/2a Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 28, 2021 (Actual)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wave Life Sciences Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 1b/2a 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
Detailed Description
The study will include approximately 15 patients. An initial cohort will receive ascending doses of WVE-N531. Up to 4 dose levels (administered ≥4 weeks apart) will be evaluated in order to select a dose level for further multiple dose evaluation. The initial patients will receive up to 3 additional doses every other week at that dose level. Additional patients will then be enrolled and dosed every other week at that level. All patients will receive a maximum of 7 total doses followed by a minimum 8 week safety monitoring period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
WVE-N531
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
WVE-N531
Intervention Description
WVE-N531 is an antisense oligonucleotide (ASO)
Primary Outcome Measure Information:
Title
Safety: Proportion of patients with adverse events (AEs)
Time Frame
Day 1 (initial dose) to a minimum of 8 weeks after the last dose
Secondary Outcome Measure Information:
Title
Pharmacokinetics: Concentration of WVE-N531 in muscle tissue
Time Frame
Day 1 (initial dose) through 2 weeks after the last dose
Title
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
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
Ambulatory or non-ambulatory male
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase.
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).
Stable pulmonary and cardiac function, as measured by the following:
Reproducible percent predicted forced vital capacity (FVC) ≥50%;
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) or cardiac magnetic resonance imaging (MRI), within 6 months prior to enrollment into the study.
Adequate deltoid muscle at Screening to perform open muscle biopsies.
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.
Exclusion Criteria:
Cardiac insufficiency:
Severe cardiomyopathy that, in the opinion of the Investigator, prohibits participation in this study; however, cardiomyopathy that is managed by angiotensin-converting-enzyme (ACE) inhibitors or beta blockers is acceptable provided the participant meets the LVEF inclusion criterion.
Any other evidence of clinically significant structural or functional heart abnormality.
Need for daytime mechanical or noninvasive ventilation OR anticipated need for daytime mechanical or noninvasive ventilation within the next year in the opinion of the Investigator. Nighttime noninvasive ventilation is permitted.
Received prior treatment with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) or drisapersen.
Received prior treatment with gene therapy for DMD.
Received treatment with ataluren, viltolarsen, eteplirsen, or golodirsen within the 14 weeks prior to Screening.
Received any investigational drug within 3 months or 5 half-lives, whichever is longer prior to Screening.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Operations
Phone
855-215-4687
Email
clinicaltrials@wavelifesci.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director, MD
Organizational Affiliation
Wave Life Sciences
Official's Role
Study Director
Facility Information:
Facility Name
London Health Sciences Centre - Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Craig Campbell, MD MSC FRCPC
Phone
519-685-8500
Ext
56216
Email
Craig.Campbell@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Cara Grobbecker
Phone
519-685-8500
Ext
56216
Email
Cara.Grobbecker@lhsc.on.ca
First Name & Middle Initial & Last Name & Degree
Craig Campbell, MD MSC FRCPC
Facility Name
Oxford Children's Hospital, Oxford University Hospitals NHS Foundation Trust
City
Headington
State/Province
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurent Servais, MD, PhD
Phone
01865 227503
Email
Laurent.Servais@ouh.nhs.uk
First Name & Middle Initial & Last Name & Degree
Laurent Servais, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Open-label Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy
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