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

April 11, 2024 updated by: Sarepta Therapeutics, Inc.

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

160

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Sarepta Therapeutics Inc. For Clinical Trial Information, Select Option 4
  • Phone Number: 1-888-SAREPTA (1-888-727-3782)
  • Email: SareptAlly@sarepta.com

Study Locations

  • Colombia
      • Bogotá, Colombia, 110231
        • Hospital Universitario San Ignacio
      • Medellin, Colombia, 50034
        • Hospital Pablo Tobon Uribe
      • Medellin, Colombia, 50012
        • Instituto Neurologico de Colombia (INDEC)
  • Czechia
      • Brno, Czechia, 613 00
        • Brno Klinika detske neurologie
      • Praha 5, Czechia, 150 06
        • Fakultni nemocnice v Motole
  • Denmark
      • Copenhagen, Denmark, 2100
        • Rigshospitalet Copenhagen University Hospital
  • France
      • Bron, France, 69677
        • Hôpital Femme Mère Enfant
      • Paris, France, 75571
        • Hopital Armand Trousseau
      • Strasbourg, France, 67098
        • CHRU de Strasbourg
  • Germany
      • Berlin, Germany, 13353
        • Charité Universitätsmedizin Berlin CVK
      • Essen, Germany, 45147
        • Universitatsklinikum Essen
      • Freiburg, Germany, 79106
        • Universitätsklinikum Freiburg
  • Greece
    • Attiki
      • Marousi, Attiki, Greece, 151 23
        • IASO Children's Hospital
  • Hungary
      • Budapest, Hungary, 1082
        • Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete
  • India
      • Ahmedabad, India, 380054
        • Royal Institute of Child Neurosciences
      • Bengaluru, India, 560078
        • Aster RV Hospital
      • Hyderabad, India, 500082
        • Nizam's Institute of Medical Sciences
      • Madurai, India, 626022
        • Jaicare Hospital (A Unit of Sarvee Integra Pvt Ltd.)
      • New Delhi, India, 110029
        • All India Institute of Medical Sciences
      • New Delhi, India, 110060
        • Sir Ganga Ram Hospital
      • Pune, India, 411004
        • Deenanath Mangeshkar Hospital & Research Centre
      • Vellore, India, 632004
        • Christian Medical College
  • Ireland
      • Dublin 1, Ireland, D01 XD99
        • Children's Health Ireland (CHI) at Temple Street
  • Italy
      • Genova, Italy, 16147
        • IRCCS Instituto Gianna Gaslini
      • Rome, Italy, 00168
        • Fondazione Policlinico Universitario A. Gemelli- IRCCS
  • Jordan
      • Amman, Jordan, 11194
        • The Specialty Hospital (TSH)/Advanced Clinical Center
      • Amman, Jordan, 11196
        • Istiklal Hosptial (IST)
      • Irbid, Jordan, 22110
        • Irbid Specialty Hospital
      • Irbid, Jordan, 22110
        • Pharmaceutical Research Center/Jordan University of Science and Technology
  • Korea, Republic of
      • Daegu, Korea, Republic of, 41404
        • Kyungpook National University Chilgok Hospital
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 6351
        • Samsung Medical Center
      • Yangsan, Korea, Republic of, 50612
        • Pusan National University Yangsan Hospital
  • Mexico
      • Durango, Mexico, 34000
        • Instituto de Investigaciones Clinicas para la Salud A.C
    • Sinaloa
      • Culiacán, Sinaloa, Mexico, 80020
        • Neurociencias Estudios Clinicos S.C.
  • Netherlands
      • Leiden, Netherlands, 2333 ZC
        • Leids Universitair Medisch Centrum
      • Nijmegen, Netherlands, 6525GA
        • Radboud University Nijmegen Medical Centre
  • New Zealand
      • Auckland, New Zealand, 1010
        • New Zealand Clinical Research - Auckland
  • Norway
      • Oslo, Norway, 0450
        • Oslo Universitetssykehus HF Rikshospitalet
      • Stavanger, Norway, 4011
        • Children's Department and Department for Children's Habilitation at Stavanger University Hospital
  • Poland
    • Pomorskie
      • Gdansk, Pomorskie, Poland, 80-211
        • Klinika Neurologii Rozwojowej
  • Romania
      • Bucharest, Romania, 41408
        • National Clinical Hospital for Children Neurorehabilitation "Dr. Nicolae Robănescu"
  • Serbia
      • Belgrade, Serbia, 11000
        • University Children's Hospital
      • Belgrade, Serbia, 11000
        • Clinic for Neurology and Psychiatry for Children and Youth
      • Belgrade, Serbia, 190133
        • Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic"
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • University Medical Centre Ljubljana
  • Spain
      • Barcelona, Spain, 8950
        • Hospital Sant Joan De Deu
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe de Valencia
  • Switzerland
      • Basel, Switzerland, 4031
        • Universitatsspital Basel
  • Taiwan
      • Kaohsiung, Taiwan, 80756
        • Kaohsiung Medical University
      • Taipei, Taiwan, 10071
        • National Taiwan University Hospital
  • Turkey
      • Antalya, Turkey, 07059
        • Akdeniz Universitesi Tip Fakultesi
      • Mersin, Turkey, 33110
        • Mersin University Medical Faculty
  • United Kingdom
      • Birmingham, United Kingdom, B9 5SS
        • Birmingham Heartlands Hospital
      • London, United Kingdom, WC1N 1EH
        • UCL Institute of Child Health Great Ormond Street
    • West Yorkshire
      • Leeds, West Yorkshire, United Kingdom, LS1 3EX
        • Leeds Teaching Hospitals NHS Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Florida
      • Gainesville, Florida, United States, 32610-3010
        • University of Florida
    • Georgia
      • Atlanta, Georgia, United States, 30318
        • Rare Disease Research, LLC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 13 years (Child)

Accepts Healthy Volunteers

No

Description

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; 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS
Active Comparator: Part 2: Eteplirsen 30 mg/kg
Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS
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.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS
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.
Drug: Eteplirsen
Solution for intravenous (IV) infusion.
Other Names:
  • AVI-4658
  • EXONDYS 51
  • EXONDYS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Part 1: Incidence of Adverse Events (AEs)
Time Frame: Up to Week 148
Up to Week 148
Part 2: Change From Baseline in the NSAA Total Score at Week 144
Time Frame: Baseline, Week 144
Baseline, Week 144

Secondary Outcome Measures

Outcome Measure
Time Frame
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
Time Frame: Baseline, Week 144
Baseline, Week 144
Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT)
Time Frame: Baseline, Week 144
Baseline, Week 144
Part 2: Change from Baseline in Forced Vital Capacity Percent Predicted (FVC%p) at Week 144
Time Frame: Baseline, Week 144
Baseline, Week 144
Part 2: Time to Loss of Ambulation (LOA)
Time Frame: Baseline up to Week 144
Baseline up to Week 144
Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression
Time Frame: Baseline, Postdose (at Week 24, Week 48, or Week 144)
Baseline, Postdose (at Week 24, Week 48, or Week 144)
Part 2: Incidence of Adverse Events (AEs)
Time Frame: Baseline up to Week 148
Baseline up to Week 148
Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen
Time Frame: 0 (predose) to 2 hours postdose up to Week 144
0 (predose) to 2 hours postdose up to Week 144

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sarepta Therapeutics, Inc.

Investigators

  • Study Director: Medical Director, Sarepta Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 13, 2020

Primary Completion (Estimated)

November 30, 2024

Study Completion (Estimated)

November 30, 2024

Study Registration Dates

First Submitted

June 18, 2019

First Submitted That Met QC Criteria

June 18, 2019

First Posted (Actual)

June 20, 2019

Study Record Updates

Last Update Posted (Estimated)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4658-402

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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