Efficacy and Safety Study of WVE-210201 (Suvodirsen) With Open-label Extension in Ambulatory Patients With Duchenne Muscular Dystrophy

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)

Status

Terminated

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03907072

Acronym

DYSTANCE 51

Enrollment

Registered

2019-04-08

Start date

2019-09-04

Completion date

2020-01-09

Last updated

2021-05-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Duchenne Muscular Dystrophy

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)

Interventions

DRUGWVE-210201 (suvodirsen)

WVE-210201 is a stereopure antisense oligonucleotide (ASO)

DRUGPlacebo

Buffered saline solution

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

MALE

Age

5 Years to 12 Years

Healthy volunteers

Inclusion criteria

1. Diagnosis of DMD based on clinical phenotype with increased serum creatine kinase 2. Documented mutation in the Dystrophin gene associated with DMD that is amenable to exon 51 skipping 3. 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) 4. Stable pulmonary and cardiac function, as measured by: 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 5. 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

1. Cardiac insufficiency: 1. 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 2. Any other evidence of clinically significant structural or functional heart abnormality 3. A cardiac troponin I value \> 0.2 ng/mL 2. 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 3. Received prior treatment with drisapersen or with an investigational peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) 4. Received prior treatment with gene therapy for DMD 5. Received treatment with ataluren or eteplirsen within the 14 weeks prior to the planned Baseline biopsy collection 6. Received any investigational drug within 3 months or 5 half-lives, whichever is longer, prior to the planned Baseline biopsy collection

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Dystrophin Level (% Normal Dystrophin)	Day 1 to Week 12, Week 22, or Week 46	US/other regions (as applicable)
Change From Baseline in North Star Ambulatory Assessment (NSAA)	Day 1 through Week 48	European Union (EU)/other regions (as applicable)

Secondary

Measure	Time frame	Description
Change From Baseline in Upper Limb Proximal Strength	Day 1 through Week 48	—
Change From Baseline in 4-stair Climb	Day 1 through Week 48	—
Change From Baseline in the 10-meter Walk/Run Test	Day 1 through Week 48	—
Change From Baseline in North Star Ambulatory Assessment (NSAA)	Day 1 through Week 48	US/other regions (as applicable)
Change From Baseline in the 95th Percentile of Stride Velocity	Day 1 through Week 48	—
Change From Baseline in NSAA	Day 1 through Week 96	Long-term evaluation, open label from Week 48 through Week 96
Change From Baseline in Forced Vital Capacity	Day 1 through Week 48	—
Change From Baseline in Dystrophin Level (% Normal Dystrophin)	Day 1 to Week 12, Week 22, or Week 46	European Union (EU)/other regions (as applicable)

Countries

Belgium, Canada, Czechia, France, Italy, Sweden, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
WVE-210201 (3 mg/kg) WVE-210201 (suvodirsen): WVE-210201 is a stereopure antisense oligonucleotide (ASO)	2
WVE-210201 (4.5 mg/kg) WVE-210201 (suvodirsen): WVE-210201 is a stereopure antisense oligonucleotide (ASO)	2
Placebo Placebo: Buffered saline solution	2
Total	6

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Study Terminated by Sponsor	2	2	2

Baseline characteristics

Characteristic	WVE-210201 (4.5 mg/kg)	Placebo	WVE-210201 (3 mg/kg)	Total
Age, Categorical <=18 years	2 Participants	2 Participants	2 Participants	6 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Continuous	9 Years	7 Years	6.5 Years	7.5 Years
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) White	2 Participants	2 Participants	1 Participants	5 Participants
Region of Enrollment Belgium	0 participants	0 participants	1 participants	1 participants
Region of Enrollment France	1 participants	0 participants	1 participants	2 participants
Region of Enrollment Italy	0 participants	2 participants	0 participants	2 participants
Region of Enrollment Sweden	1 participants	0 participants	0 participants	1 participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	2 Participants	2 Participants	2 Participants	6 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 2	0 / 2	0 / 2
other Total, other adverse events	2 / 2	2 / 2	2 / 2
serious Total, serious adverse events	0 / 2	1 / 2	0 / 2

Outcome results

Primary

Change From Baseline in Dystrophin Level (% Normal Dystrophin)

US/other regions (as applicable)

Time frame: Day 1 to Week 12, Week 22, or Week 46

Population: No statistical analysis has been performed due to early study termination

Primary