Back to resultsEfficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy (DYSTANCE 51)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
WVE-210201 (suvodirsen)
Placebo
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 Dystrophin gene associated with DMD that is amenable to exon 51 skipping
- Ambulatory male, able to walk independently for at least 10 meters in 10 seconds or less at the time of Screening visit (performed as part of the NSAA)
Stable pulmonary and cardiac function, as measured by:
- 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
- Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy occurred ≥6 months prior to Screening, and no changes in dosing ≤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 patient meets the LVEF inclusion criterion
- Any other evidence of clinically significant structural or functional heart abnormality
- A cardiac troponin I value > 0.2 ng/mL
- Need for daytime mechanical or non-invasive ventilation OR anticipated need for daytime mechanical or non-invasive ventilation within the next year, in the opinion of the Investigator. Nighttime non-invasive ventilation is permitted
- Received prior treatment with drisapersen or with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)
- Received prior treatment with gene therapy for DMD
- Received treatment with ataluren or eteplirsen within the 14 weeks prior to the planned Baseline biopsy collection
- Received any investigational drug within 3 months or 5 half-lives, whichever is longer, prior to the planned Baseline biopsy collection
Sites / Locations
- Yale University
- Rare Disease Research, LLC.
- University of Kansas Medical Center
- Kennedy Krieger Institute
- University of Massachusetts
- Children's Hospital of Wisconsin
- Institut de Myologie
- UZ Gent
- Universitaire Ziekenhuizen Leuven
- Alberta Children's Hospital
- London Health Sciences Centre - Hospital
- Fakultni Nemocnice v Motole
- Hôpitaux Universitaires de Strasbourg
- Hôpital Des Enfants
- Hopital Armand Trosseau
- Ospedale Pediatrico Bambino Gesù
- U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud
- Ospedale San Reffaele Via Olgettina, 60
- Fondazione Policlinico Universitario A Gemelli
- Drottning Silvias Barn Och Ungdomssjukhus
- Leeds Teaching Hospitals NHS Trust
- Great Ormond Street Hospital (GOSH)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
WVE-210201 (3 mg/kg)
WVE-210201 (4.5 mg/kg)
Placebo
Arm Description
Weekly IV administrations of WVE-210210 at 3 mg/kg
Weekly IV administrations of WVE-210210 at 4.5 mg/kg
Weekly IV administrations of phosphate buffered saline solution visually identical in appearance to WVE-21021
Outcomes
Primary Outcome Measures
Change From Baseline in Dystrophin Level (% Normal Dystrophin)
US/other regions (as applicable)
Change From Baseline in North Star Ambulatory Assessment (NSAA)
European Union (EU)/other regions (as applicable)
Secondary Outcome Measures
Change From Baseline in North Star Ambulatory Assessment (NSAA)
US/other regions (as applicable)
Change From Baseline in Dystrophin Level (% Normal Dystrophin)
European Union (EU)/other regions (as applicable)
Change From Baseline in Upper Limb Proximal Strength
Change From Baseline in 4-stair Climb
Change From Baseline in the 10-meter Walk/Run Test
Change From Baseline in Forced Vital Capacity
Change From Baseline in the 95th Percentile of Stride Velocity
Change From Baseline in NSAA
Long-term evaluation, open label from Week 48 through Week 96
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03907072
Brief Title
Efficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy
Acronym
DYSTANCE 51
Official Title
A Randomized, Double-blind, Placebo-controlled, Efficacy and Safety Study of WVE-210201 With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy (DYSTANCE 51)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Terminated
Why Stopped
Lack of efficacy
Study Start Date
September 4, 2019 (Actual)
Primary Completion Date
December 16, 2019 (Actual)
Study Completion Date
January 9, 2020 (Actual)
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2/3, multicenter, randomized, double-blind, placebo-controlled study with an open-label extension period to evaluate the safety and efficacy of WVE-210201 (suvodirsen) in ambulatory male pediatric patients with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping intervention (DYSTANCE 51)
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 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
6 (Actual)
8. Arms, Groups, and Interventions
Arm Title
WVE-210201 (3 mg/kg)
Arm Type
Experimental
Arm Description
Weekly IV administrations of WVE-210210 at 3 mg/kg
Arm Title
WVE-210201 (4.5 mg/kg)
Arm Type
Experimental
Arm Description
Weekly IV administrations of WVE-210210 at 4.5 mg/kg
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Weekly IV administrations of phosphate buffered saline solution visually identical in appearance to WVE-21021
Intervention Type
Drug
Intervention Name(s)
WVE-210201 (suvodirsen)
Intervention Description
WVE-210201 is a stereopure antisense oligonucleotide (ASO)
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Buffered saline solution
Primary Outcome Measure Information:
Title
Change From Baseline in Dystrophin Level (% Normal Dystrophin)
Description
US/other regions (as applicable)
Time Frame
Day 1 to Week 12, Week 22, or Week 46
Title
Change From Baseline in North Star Ambulatory Assessment (NSAA)
Description
European Union (EU)/other regions (as applicable)
Time Frame
Day 1 through Week 48
Secondary Outcome Measure Information:
Title
Change From Baseline in North Star Ambulatory Assessment (NSAA)
Description
US/other regions (as applicable)
Time Frame
Day 1 through Week 48
Title
Change From Baseline in Dystrophin Level (% Normal Dystrophin)
Description
European Union (EU)/other regions (as applicable)
Time Frame
Day 1 to Week 12, Week 22, or Week 46
Title
Change From Baseline in Upper Limb Proximal Strength
Time Frame
Day 1 through Week 48
Title
Change From Baseline in 4-stair Climb
Time Frame
Day 1 through Week 48
Title
Change From Baseline in the 10-meter Walk/Run Test
Time Frame
Day 1 through Week 48
Title
Change From Baseline in Forced Vital Capacity
Time Frame
Day 1 through Week 48
Title
Change From Baseline in the 95th Percentile of Stride Velocity
Time Frame
Day 1 through Week 48
Title
Change From Baseline in NSAA
Description
Long-term evaluation, open label from Week 48 through Week 96
Time Frame
Day 1 through Week 96
10. Eligibility
Sex
Male
Gender Based
Yes
Minimum Age & Unit of Time
5 Years
Maximum Age & Unit of Time
12 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 Dystrophin gene associated with DMD that is amenable to exon 51 skipping
Ambulatory male, able to walk independently for at least 10 meters in 10 seconds or less at the time of Screening visit (performed as part of the NSAA)
Stable pulmonary and cardiac function, as measured by:
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
Currently on a stable corticosteroid therapy regimen, defined as initiation of systemic corticosteroid therapy occurred ≥6 months prior to Screening, and no changes in dosing ≤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 patient meets the LVEF inclusion criterion
Any other evidence of clinically significant structural or functional heart abnormality
A cardiac troponin I value > 0.2 ng/mL
Need for daytime mechanical or non-invasive ventilation OR anticipated need for daytime mechanical or non-invasive ventilation within the next year, in the opinion of the Investigator. Nighttime non-invasive ventilation is permitted
Received prior treatment with drisapersen or with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)
Received prior treatment with gene therapy for DMD
Received treatment with ataluren or eteplirsen within the 14 weeks prior to the planned Baseline biopsy collection
Received any investigational drug within 3 months or 5 half-lives, whichever is longer, prior to the planned Baseline biopsy collection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael A Panzara, MD, MPH
Organizational Affiliation
Wave Life Sciences
Official's Role
Study Director
Facility Information:
Facility Name
Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Rare Disease Research, LLC.
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
University of Massachusetts
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Children's Hospital of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Institut de Myologie
City
Liège
State/Province
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Universitaire Ziekenhuizen Leuven
City
Leuven
Country
Belgium
Facility Name
Alberta Children's Hospital
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T3B6A8
Country
Canada
Facility Name
London Health Sciences Centre - Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Facility Name
Fakultni Nemocnice v Motole
City
Praha 5
ZIP/Postal Code
15006
Country
Czechia
Facility Name
Hôpitaux Universitaires de Strasbourg
City
Strasbourg
State/Province
Bas-Rhin
ZIP/Postal Code
67098
Country
France
Facility Name
Hôpital Des Enfants
City
Toulouse
State/Province
Haute-Garonne
ZIP/Postal Code
31059
Country
France
Facility Name
Hopital Armand Trosseau
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
Ospedale Pediatrico Bambino Gesù
City
Roma
State/Province
Lazio
ZIP/Postal Code
165
Country
Italy
Facility Name
U.O.C di Neurologia e Malattie Neuromuscolari Centro Clinico Nemo Sud
City
Messina
ZIP/Postal Code
98125
Country
Italy
Facility Name
Ospedale San Reffaele Via Olgettina, 60
City
Milano
ZIP/Postal Code
20132
Country
Italy
Facility Name
Fondazione Policlinico Universitario A Gemelli
City
Roma
ZIP/Postal Code
8, 00168
Country
Italy
Facility Name
Drottning Silvias Barn Och Ungdomssjukhus
City
Göteborg
ZIP/Postal Code
41650
Country
Sweden
Facility Name
Leeds Teaching Hospitals NHS Trust
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Great Ormond Street Hospital (GOSH)
City
London
ZIP/Postal Code
WC1N EH
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Efficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy
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