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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03992430




Registration number
NCT03992430
Ethics application status
Date submitted
18/06/2019
Date registered
20/06/2019
Date last updated
15/04/2024

Titles & IDs
Public title
A Study to Compare Safety and Efficacy of a High Dose of Eteplirsen in Participants With Duchenne Muscular Dystrophy (DMD) (MIS51ON)
Scientific title
A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of a High Dose of Eteplirsen, Preceded by an Open-label Dose Escalation, in Patients With Duchenne Muscular Dystrophy With Deletion Mutations Amenable to Exon 51 Skipping
Secondary ID [1] 0 0
4658-402
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Muscular Dystrophy, Duchenne 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Eteplirsen

Experimental: Part 1: Eteplirsen - Participants will receive eteplirsen 100 mg/kg once weekly for at least 4 weeks, followed by eteplirsen 200 mg/kg once weekly for at least 4 weeks.

Active comparator: Part 2: Eteplirsen 30 mg/kg - Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.

Experimental: Part 2: Eteplirsen 100 mg/kg - Randomized participants will receive eteplirsen 100 mg/kg once weekly before the selection of the high dose occurs and then will receive the selected high dose once weekly for up to 144 weeks.

Experimental: Part 2: Eteplirsen 200 mg/kg - Randomized participants will receive eteplirsen 200 mg/kg once weekly before the selection of the high dose occurs and then will receive the selected high dose once weekly for up to 144 weeks.


Treatment: Drugs: Eteplirsen
Solution for intravenous (IV) infusion.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Incidence of Adverse Events (AEs)
Timepoint [1] 0 0
Up to Week 148
Primary outcome [2] 0 0
Part 2: Change From Baseline in the NSAA Total Score at Week 144
Timepoint [2] 0 0
Baseline, Week 144
Secondary outcome [1] 0 0
Part 2: Change From Baseline in Time to Rise From the Floor, Time to Complete 10-Meter Walk/Run, and the Timed Stair Ascend Test
Timepoint [1] 0 0
Baseline, Week 144
Secondary outcome [2] 0 0
Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT)
Timepoint [2] 0 0
Baseline, Week 144
Secondary outcome [3] 0 0
Part 2: Change from Baseline in Forced Vital Capacity Percent Predicted (FVC%p) at Week 144
Timepoint [3] 0 0
Baseline, Week 144
Secondary outcome [4] 0 0
Part 2: Time to Loss of Ambulation (LOA)
Timepoint [4] 0 0
Baseline up to Week 144
Secondary outcome [5] 0 0
Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression
Timepoint [5] 0 0
Baseline, Postdose (at Week 24, Week 48, or Week 144)
Secondary outcome [6] 0 0
Part 2: Incidence of Adverse Events (AEs)
Timepoint [6] 0 0
Baseline up to Week 148
Secondary outcome [7] 0 0
Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen
Timepoint [7] 0 0
0 (predose) to 2 hours postdose up to Week 144

Eligibility
Key inclusion criteria
* Be a male with an established clinical diagnosis of DMD and an out-of-frame deletion mutation of the DMD gene amenable to exon 51 skipping.
* Ambulatory participant, able to perform TTRISE in 10 seconds or less at the time of screening visit.
* Able to walk independently without assistive devices.
* Have intact right and left biceps muscles or an alternative upper arm muscle group.
* Have been on a stable dose or dose equivalent of oral corticosteroids for at least 12 weeks prior to randomization and the dose is expected to remain constant (except for modifications to accommodate changes in weight and stress-related needs as per the recently published guidelines throughout the study.
* For ages 7 years and older, has stable pulmonary function (forced vital capacity =50 percent (%) of predicted and no requirement for nocturnal ventilation). For ages 4 to 6 years, does not require support from ventilator or non-invasive ventilation at time of screening.
Minimum age
4 Years
Maximum age
13 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
* Use of any pharmacologic treatment (other than corticosteroids) within 12 weeks prior to randomization.
* Current or previous treatment with any other experimental pharmacologic treatment for DMD or any prior exposure to antisense oligonucleotide, gene therapy or gene editing; except the following: Ezutromid in the last 12 weeks prior to first dose; Drisapersen in the last 36 weeks prior to first dose; Suvodirsen in the last 12 weeks prior to first dose; Vamorolone in the last 12 weeks prior to first dose; and Eteplirsen (previous or current use).
* Major surgery within 3 months prior to randomization.
* Presence of any other significant neuromuscular or genetic disease other than DMD.
* Presence of any known impairment of renal function and/or other clinically significant illness.
* Has evidence of cardiomyopathy, as defined by left ventricular ejection fraction less than <50% on the screening echocardiogram or Fridericia's correction formula (QTcF) =450 millisecond based on the screening electrocardiograms (ECGs).

Other inclusion/exclusion criteria apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/11/2024
Actual
Sample size
Target
Accrual to date
Final
160
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
Colombia
State/province [4] 0 0
Bogotá
Country [5] 0 0
Colombia
State/province [5] 0 0
Medellin
Country [6] 0 0
Czechia
State/province [6] 0 0
Brno
Country [7] 0 0
Czechia
State/province [7] 0 0
Praha 5
Country [8] 0 0
Denmark
State/province [8] 0 0
Copenhagen
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France
State/province [9] 0 0
Bron
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France
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Paris
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France
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Strasbourg
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Germany
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Berlin
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Germany
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Essen
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Germany
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Freiburg
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Greece
State/province [15] 0 0
Attiki
Country [16] 0 0
Hungary
State/province [16] 0 0
Budapest
Country [17] 0 0
India
State/province [17] 0 0
Ahmedabad
Country [18] 0 0
India
State/province [18] 0 0
Bengaluru
Country [19] 0 0
India
State/province [19] 0 0
Hyderabad
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India
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Madurai
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India
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New Delhi
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India
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Pune
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India
State/province [23] 0 0
Vellore
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Ireland
State/province [24] 0 0
Dublin 1
Country [25] 0 0
Italy
State/province [25] 0 0
Genova
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Italy
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Rome
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Jordan
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Amman
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Jordan
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Irbid
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Korea, Republic of
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Daegu
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Korea, Republic of
State/province [30] 0 0
Seoul
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Korea, Republic of
State/province [31] 0 0
Yangsan
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Mexico
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Sinaloa
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Mexico
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Durango
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Netherlands
State/province [34] 0 0
Leiden
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Netherlands
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Nijmegen
Country [36] 0 0
New Zealand
State/province [36] 0 0
Auckland
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Norway
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Oslo
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Norway
State/province [38] 0 0
Stavanger
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Poland
State/province [39] 0 0
Pomorskie
Country [40] 0 0
Romania
State/province [40] 0 0
Bucharest
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Serbia
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Belgrade
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Slovenia
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Ljubljana
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Spain
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Barcelona
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Spain
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Valencia
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Switzerland
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Basel
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Taiwan
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Kaohsiung
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Taiwan
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Taipei
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Turkey
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Antalya
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Turkey
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Mersin
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United Kingdom
State/province [50] 0 0
West Yorkshire
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Birmingham
Country [52] 0 0
United Kingdom
State/province [52] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sarepta Therapeutics, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will be comprised of 2 parts: Part 1 (dose escalation) will be conducted to evaluate the safety and tolerability of 2 doses (100 milligrams/kilogram \[mg/kg\] and 200 mg/kg) of eteplirsen in approximately 10 participants with DMD; Part 2 (dose finding and dose comparison) will be conducted for the selection of a high dose (100 mg/kg versus 200 mg/kg) and its comparison with the 30 mg/kg dose of eteplirsen, in approximately 144 participants with genetically confirmed deletion mutations amenable to treatment by skipping exon 51.
Trial website
https://clinicaltrials.gov/study/NCT03992430
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Sarepta Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03992430