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

NCT03992430 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: 4658-4022018-001762-422024-511492-15-00
• Study Type: interventional
• Target: 160
• Locations: 26 countries
• Sites: 59

Brief Summary

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.

Conditions

Muscular Dystrophy, Duchenne

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Part 1: Incidence of Adverse Events (AEs)

  Up to Week 148

• Part 2: Change From Baseline at Week 144 in the NSAA Total Score (for Final Analysis)

  Baseline, Week 144

• Part 2: Change from Baseline at Week 72 or Week 96 in NSAA Total Score (for Conditional Efficacy Interim Analysis)

  Baseline, Week 72 or Week 96

Secondary Outcomes (7)

• 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

  Baseline, Week 144

• Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT)

  Baseline, Week 144

• Part 2: Change from Baseline at Week 144 in Forced Vital Capacity Percent Predicted (FVC%p)

  Baseline, Week 144

• Part 2: Time to Loss of Ambulation (LOA)

  Baseline up to Week 144

• Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression

  Baseline, Postdose (at Week 24, Week 48, or Week 144)

Study Arms (4)

Part 1: Eteplirsen

EXPERIMENTAL

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.

Drug: Eteplirsen

Part 2: Eteplirsen 30 mg/kg

ACTIVE COMPARATOR

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

Drug: Eteplirsen

Part 2: Eteplirsen 100 mg/kg

EXPERIMENTAL

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

Drug: Eteplirsen

Part 2: Eteplirsen 200 mg/kg

EXPERIMENTAL

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

Drug: Eteplirsen

Interventions

Eteplirsen DRUG

Solution for intravenous (IV) infusion.

Also known as: AVI-4658, EXONDYS 51, EXONDYS

Part 1: Eteplirsen; Part 2: Eteplirsen 100 mg/kg; Part 2: Eteplirsen 200 mg/kg; Part 2: Eteplirsen 30 mg/kg

Eligibility Criteria

• Age: 4 Years - 13 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead

Study Sites (59)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of Florida

Gainesville, Florida, 32610-3010, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30318, United States

Location

Hospital Universitario San Ignacio

Bogotá, 110231, Colombia

Location

Instituto Neurologico de Colombia (INDEC)

Medellín, 50012, Colombia

Location

Hospital Pablo Tobón Uribe

Medellín, 50034, Colombia

Location

Brno Klinika detske neurologie

Brno, 613 00, Czechia

Location

Fakultni nemocnice v Motole

Prague, 150 06, Czechia

Location

Rigshospitalet Copenhagen University Hospital

Copenhagen, 2100, Denmark

Location

Hopital Femme Mere Enfant

Bron, 69677, France

Location

Hopital Armand Trousseau

Paris, 75571, France

Location

CHRU de Strasbourg

Strasbourg, 67098, France

Location

Charité Universitätsmedizin Berlin CVK

Berlin, 13353, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

IASO Children's Hospital

Marousi, Attica, 151 23, Greece

Location

Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete

Budapest, 1082, Hungary

Location

Royal Institute of Child Neurosciences

Ahmedabad, 380054, India

Location

Aster RV Hospital

Bengaluru, 560078, India

Location

Nizam's Institute of Medical Sciences

Hyderabad, 500082, India

Location

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

Madurai, 626022, India

Location

All India Institute of Medical Sciences

New Delhi, 110029, India

Location

Sir Ganga Ram Hospital

New Delhi, 110060, India

Location

Deenanath Mangeshkar Hospital & Research Centre

Pune, 411004, India

Location

Christian Medical College

Vellore, 632004, India

Location

Children's Health Ireland (CHI) at Temple Street

Dublin, D01 XD99, Ireland

Location

IRCCS Instituto Gianna Gaslini

Genova, 16147, Italy

Location

Fondazione Policlinico Universitario A. Gemelli- IRCCS

Rome, 00168, Italy

Location

The Specialty Hospital (TSH)/Advanced Clinical Center

Amman, 11194, Jordan

Location

Istiklal Hosptial (IST)

Amman, 11196, Jordan

Location

Irbid Specialty Hospital

Irbid, 22110, Jordan

Location

Pharmaceutical Research Center/Jordan University of Science and Technology

Irbid, 22110, Jordan

Location

Neurociencias Estudios Clínicos S.C.

Culiacán, Sinaloa, 80020, Mexico

Location

Instituto de Investigaciones Clinicas para la Salud A.C

Durango, 34000, Mexico

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZC, Netherlands

Location

Radboud University Nijmegen Medical Centre

Nijmegen, 6525GA, Netherlands

Location

New Zealand Clinical Research - Auckland

Auckland, 1010, New Zealand

Location

Oslo Universitetssykehus HF Rikshospitalet

Oslo, 0450, Norway

Location

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

Stavanger, 4011, Norway

Location

Klinika Neurologii Rozwojowej

Gdansk, Pomeranian Voivodeship, 80-211, Poland

Location

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

Bucharest, 41408, Romania

Location

Clinic for Neurology and Psychiatry for Children and Youth

Belgrade, 11000, Serbia

Location

University Children's Hospital

Belgrade, 11000, Serbia

Location

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

Belgrade, 190133, Serbia

Location

University Medical Centre Ljubljana

Ljubljana, 1000, Slovenia

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

Hospital Sant Joan de Deu

Barcelona, 8950, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

Universitätsspital Basel

Basel, 4031, Switzerland

Location

Kaohsiung Medical University

Kaohsiung City, 80756, Taiwan

Location

National Taiwan University Hospital

Taipei, 10071, Taiwan

Location

Akdeniz Universitesi Tip Fakultesi

Antalya, 07059, Turkey (Türkiye)

Location

Mersin University Medical Faculty

Mersin, 33110, Turkey (Türkiye)

Location

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS1 3EX, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

UCL Institute of Child Health Great Ormond Street

London, WC1N 1EH, United Kingdom

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

eteplirsen

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Medical Director

  Sarepta Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 is open-label, dose escalation; Part 2 is double-blind, dose finding, and dose comparison
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: July 13, 2020
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

SL (1); RO (1); NL (2); KR (4); CH (1); FR (3); NZ (1); IE (1); DE (3); IT (2); HU (1); CO (3); SE (3); CZ (2); ES (2); ME (2); TW (2); TU (2); GB (3); GR (1); US (3); PL (1); IN (8); DK (1); JO (4); NO (2)