A Study to Compare Safety and Efficacy of High Doses of Eteplirsen in Participants With Duchenne Muscular Dystrophy (DMD) (MIS51ON)

NCT ID: NCT03992430

Last Updated: 2024-12-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

160 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-13

Study Completion Date

2026-10-31

Brief Summary

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Part 1 (dose escalation) will 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 evaluate the efficacy and safety of the high doses (100 mg/kg and 200 mg/kg) of eteplirsen compared with that of the 30 mg/kg dose of eteplirsen, in approximately 144 participants with genetically confirmed deletion mutations amenable to treatment by skipping exon 51.

Detailed Description

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Conditions

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Muscular Dystrophy, Duchenne

Keywords

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Duchenne muscular dystrophy Exon Skipping Exon 51 North Star Ambulatory Assessment Ambulatory DMD Pediatric Duchenne EXONDYS MIS51ON

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Part 1 is open-label, dose escalation; Part 2 is double-blind, dose finding, and dose comparison

Study Groups

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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.

Group Type EXPERIMENTAL

Eteplirsen

Intervention Type DRUG

Solution for intravenous (IV) infusion.

Part 2: Eteplirsen 30 mg/kg

Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.

Group Type ACTIVE_COMPARATOR

Eteplirsen

Intervention Type DRUG

Solution for intravenous (IV) infusion.

Part 2: Eteplirsen 100 mg/kg

Randomized participants will receive eteplirsen 100 mg/kg once weekly for up to 144 weeks.

Group Type EXPERIMENTAL

Eteplirsen

Intervention Type DRUG

Solution for intravenous (IV) infusion.

Part 2: Eteplirsen 200 mg/kg

Randomized participants will receive eteplirsen 200 mg/kg once weekly for up to 144 weeks.

Group Type EXPERIMENTAL

Eteplirsen

Intervention Type DRUG

Solution for intravenous (IV) infusion.

Interventions

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Eteplirsen

Solution for intravenous (IV) infusion.

Intervention Type DRUG

Other Intervention Names

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AVI-4658 EXONDYS 51 EXONDYS

Eligibility Criteria

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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.

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; Eteplirsen (previous or current use); and Tamoxifen in the last 4 weeks prior to first dose.
* 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).
Minimum Eligible Age

4 Years

Maximum Eligible Age

13 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Sarepta Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Sarepta Therapeutics, Inc.

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Rare Disease Research, LLC

Atlanta, Georgia, United States

Site Status

Hospital Universitario San Ignacio

Bogotá, , Colombia

Site Status

Instituto Neurologico de Colombia (INDEC)

Medellín, , Colombia

Site Status

Hospital Pablo Tobón Uribe

Medellín, , Colombia

Site Status

Brno Klinika detske neurologie

Brno, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Rigshospitalet Copenhagen University Hospital

Copenhagen, , Denmark

Site Status

Hopital Femme Mere Enfant

Bron, , France

Site Status

Hopital Armand Trousseau

Paris, , France

Site Status

CHRU de Strasbourg

Strasbourg, , France

Site Status

Charité Universitätsmedizin Berlin CVK

Berlin, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status

IASO Children's Hospital

Marousi, Attica, Greece

Site Status

Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete

Budapest, , Hungary

Site Status

Royal Institute of Child Neurosciences

Ahmedabad, , India

Site Status

Aster RV Hospital

Bengaluru, , India

Site Status

Nizam's Institute of Medical Sciences

Hyderabad, , India

Site Status

Jaicare Hospital (A Unit of Sarvee Integra Pvt Ltd.)

Madurai, , India

Site Status

All India Institute of Medical Sciences

New Delhi, , India

Site Status

Sir Ganga Ram Hospital

New Delhi, , India

Site Status

Deenanath Mangeshkar Hospital & Research Centre

Pune, , India

Site Status

Christian Medical College

Vellore, , India

Site Status

Children's Health Ireland (CHI) at Temple Street

Dublin, , Ireland

Site Status

IRCCS Instituto Gianna Gaslini

Genova, , Italy

Site Status

Fondazione Policlinico Universitario A. Gemelli- IRCCS

Rome, , Italy

Site Status

The Specialty Hospital (TSH)/Advanced Clinical Center

Amman, , Jordan

Site Status

Istiklal Hosptial (IST)

Amman, , Jordan

Site Status

Irbid Specialty Hospital

Irbid, , Jordan

Site Status

Pharmaceutical Research Center/Jordan University of Science and Technology

Irbid, , Jordan

Site Status

Neurociencias Estudios Clínicos S.C.

Culiacán, Sinaloa, Mexico

Site Status

Instituto de Investigaciones Clinicas para la Salud A.C

Durango, , Mexico

Site Status

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Site Status

Radboud University Nijmegen Medical Centre

Nijmegen, , Netherlands

Site Status

New Zealand Clinical Research - Auckland

Auckland, , New Zealand

Site Status

Oslo Universitetssykehus HF Rikshospitalet

Oslo, , Norway

Site Status

Children's Department and Department for Children's Habilitation at Stavanger University Hospital

Stavanger, , Norway

Site Status

Klinika Neurologii Rozwojowej

Gdansk, Pomeranian Voivodeship, Poland

Site Status

National Clinical Hospital for Children Neurorehabilitation "Dr. Nicolae Robănescu"

Bucharest, , Romania

Site Status

Clinic for Neurology and Psychiatry for Children and Youth

Belgrade, , Serbia

Site Status

University Children's Hospital

Belgrade, , Serbia

Site Status

Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic"

Belgrade, , Serbia

Site Status

University Medical Centre Ljubljana

Ljubljana, , Slovenia

Site Status

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Pusan National University Yangsan Hospital

Yangsan, , South Korea

Site Status

Hospital Sant Joan de Deu

Barcelona, , Spain

Site Status

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Site Status

Universitätsspital Basel

Basel, , Switzerland

Site Status

Kaohsiung Medical University

Kaohsiung City, , Taiwan

Site Status

National Taiwan University Hospital

Taipei, , Taiwan

Site Status

Akdeniz Universitesi Tip Fakultesi

Antalya, , Turkey (Türkiye)

Site Status

Mersin University Medical Faculty

Mersin, , Turkey (Türkiye)

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, United Kingdom

Site Status

Birmingham Heartlands Hospital

Birmingham, , United Kingdom

Site Status

UCL Institute of Child Health Great Ormond Street

London, , United Kingdom

Site Status

Countries

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Canada United States Colombia Czechia Denmark France Germany Greece Hungary India Ireland Italy Jordan Mexico Netherlands New Zealand Norway Poland Romania Serbia Slovenia South Korea Spain Switzerland Taiwan Turkey (Türkiye) United Kingdom

Other Identifiers

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2018-001762-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-511492-15-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

4658-402

Identifier Type: -

Identifier Source: org_study_id