Clinical Trials Nct-pagina

Clinical Trial Results:
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)

Summary
EudraCT number	2018-004009-22
Trial protocol	FR GB SE NL BE PL CZ DE IT
Global end of trial date	09 Jan 2020

Results information
Results version number	v1(current)
This version publication date	13 Sep 2020
First version publication date	13 Sep 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

WVE-DMDX51-003

ISRCTN number

US NCT number

NCT03907072

WHO universal trial number (UTN)

Sponsor organisation name

Wave Life Sciences UK Limited

Sponsor organisation address

1 Chamberlain Square CS, Birmingham, United Kingdom, B3 3AX

Public contact

Chief Medical Officer, Wave Life Sciences, +617 949-2900, info@wavelifesci.com

Scientific contact

Chief Medical Officer, Wave Life Sciences, +617 949-2900, info@wavelifesci.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

11 Feb 2020

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

09 Jan 2020

Was the trial ended prematurely?

Yes

Main objective of the trial

To evaluate the efficacy of WVE-210201 by assessing changes in motor function by North Star Ambulatory Assessment (NSAA) (EU/Japan).

Protection of trial subjects

Written informed consent from each patient or patient’s parent(s) or legal guardian(s), if applicable, and written assent from each patient, if applicable, were obtained before any study-specific screening or baseline period evaluations were performed. The anonymity of participating patients was maintained to the extent required by applicable laws and in accordance with current HIPAA standards. This study was designed and monitored in accordance with Sponsor procedures, which complied with the ethical principles of Good Clinical Practice (GCP) as required by the major regulatory authorities, and in accordance with the Declaration of Helsinki. A Data Monitoring Committee (DMC) was to review unblinded safety data periodically and on an ad hoc basis at least until completion of the Double-blind period. In addition, the DMC was to review the results from the planned interim analyses.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Jan 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Sweden: 1

Country: Number of subjects enrolled

Belgium: 1

Country: Number of subjects enrolled

France: 2

Country: Number of subjects enrolled

Italy: 2

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

This study was conducted in 4 countries (Italy, France, Belgium, and Sweden from 04 September 2019 to 09 January 2020).

Screening details

Screening evaluations were completed within 6 weeks of signing the informed consent form. A total of 6 subjects were screened and enrolled in study treatment.

Period 1 title

Period 1 (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Blinding implementation details

Study was conducted as randomized, placebo-controlled, and double-blind. Results for the OLE portion of the study were not reported due to early study termination.

Are arms mutually exclusive

Yes

Placebo

Arm description

Matched saline solution administered alone via IV infusion

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Matched saline solution administered alone via IV infusion

3 mg/kg WVE-210201

Arm description

3 mg/kg WVE-210201 administered via IV infusion

Arm type

Experimental

Investigational medicinal product name

Suvodirsen

Investigational medicinal product code

WVE-210201

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients received weekly IV infusions of suvodirsen or placebo. WVE-210201 was provided as an isotonic solution for dilution for infusion.

4.5 mg/kg WVE-210201

Arm description

4.5 mg/kg WVE-210201 administered via IV infusion

Arm type

Experimental

Investigational medicinal product name

Suvodirsen

Investigational medicinal product code

WVE-210201

Other name

Pharmaceutical forms

Solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Patients received weekly IV infusions of suvodirsen or placebo. WVE-210201 was provided as an isotonic solution for dilution for infusion.

Number of subjects in period 1	Placebo	3 mg/kg WVE-210201	4.5 mg/kg WVE-210201
Started	2	2	2
Completed	0	0	0
Not completed	2	2	2
Study Terminated by Sponsor	2	2	2

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Matched saline solution administered alone via IV infusion

Reporting group title

3 mg/kg WVE-210201

Reporting group description

3 mg/kg WVE-210201 administered via IV infusion

Reporting group title

4.5 mg/kg WVE-210201

Reporting group description

4.5 mg/kg WVE-210201 administered via IV infusion

Reporting group values	Placebo	3 mg/kg WVE-210201	4.5 mg/kg WVE-210201	Total
Number of subjects	2	2	2	6
Age categorical
Units: Subjects
In utero	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0
Newborns (0-27 days)	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0
Children (2-11 years)	2	2	2	6
Adolescents (12-17 years)	0	0	0	0
Adults (18-64 years)	0	0	0	0
From 65-84 years	0	0	0	0
85 years and over	0	0	0	0
Gender categorical
Units: Subjects
Female	0	0	0	0
Male	2	2	2	6

Subject analysis set title

Safety population

Subject analysis set type

Safety analysis

Subject analysis set description

All randomly assigned patients who received at least 1 dose of WVE-210201 or placebo.

Subject analysis sets values	Safety population
Number of subjects	6
Age categorical
Units: Subjects
In utero	0
Preterm newborn infants (gestational age < 37 wks)	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	6
Adolescents (12-17 years)	0
Adults (18-64 years)	0
From 65-84 years	0
85 years and over	0
Age continuous
Units:
	±
Gender categorical
Units: Subjects
Female	0
Male	6

End points

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Reporting group title

Placebo

Reporting group description

Matched saline solution administered alone via IV infusion

Reporting group title

3 mg/kg WVE-210201

Reporting group description

3 mg/kg WVE-210201 administered via IV infusion

Reporting group title

4.5 mg/kg WVE-210201

Reporting group description

4.5 mg/kg WVE-210201 administered via IV infusion

Subject analysis set title

Safety population

Subject analysis set type

Safety analysis

Subject analysis set description

All randomly assigned patients who received at least 1 dose of WVE-210201 or placebo.

Primary: Change from baseline in NSAA through 48 weeks (EU/Japan)

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End point title

Change from baseline in NSAA through 48 weeks (EU/Japan) ^[1]

End point description

The NSAA is a validated unidimensional scale, designed for measuring motor function in ambulatory boys with DMD. There are no primary endpoint results due to patients early termination.

End point type

Primary

End point timeframe

From baseline over 48 weeks

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analysis has been performed due to early study termination.

End point values	Placebo	3 mg/kg WVE-210201	4.5 mg/kg WVE-210201
Number of subjects analysed	2	2	2
Units: Subjects
number (not applicable)	2	2	2

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Day 1 to Early Termination

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

22.1

Reporting group title

Placebo

Reporting group description

Matched saline solution administered alone via IV infusion

Reporting group title

3 mg/kg WVE-210201

Reporting group description

3 mg/kg WVE-210201 administered via IV infusion

Reporting group title

4.5 mg/kg WVE-210201

Reporting group description

4.5 mg/kg WVE-210201 administered via IV infusion

Serious adverse events	Placebo	3 mg/kg WVE-210201	4.5 mg/kg WVE-210201
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Cardiac disorders
Cardiac disorder
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	3 mg/kg WVE-210201	4.5 mg/kg WVE-210201
Total subjects affected by non serious adverse events
subjects affected / exposed	2 / 2 (100.00%)	2 / 2 (100.00%)	2 / 2 (100.00%)
Injury, poisoning and procedural complications
Bone contusion
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0
Investigations
C-reactive protein increased
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	1
Nervous system disorders
Headache
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	4
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	2 / 2 (100.00%)
occurrences all number	0	3	4
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)
occurrences all number	0	1	1
Vomiting
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	4
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 2 (50.00%)	0 / 2 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0
Nasopharyngitis
subjects affected / exposed	0 / 2 (0.00%)	1 / 2 (50.00%)	1 / 2 (50.00%)
occurrences all number	0	1	1
Oral herpes
subjects affected / exposed	0 / 2 (0.00%)	0 / 2 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

09 Jul 2019

Amendment 2.0, 48-week open-label extension period added to the study.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Not applicable

Clinical Trials Nct-pagina

Clinical Trial Results:
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)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline in NSAA through 48 weeks (EU/Japan)

Primary: Change from baseline in NSAA through 48 weeks (EU/Japan)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

Clinical Trials Nct-pagina

Clinical Trial Results: 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)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline in NSAA through 48 weeks (EU/Japan)

Primary: Change from baseline in NSAA through 48 weeks (EU/Japan)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

Clinical Trial Results:
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)