A Study to Compare Safety and Efficacy of High Doses of Eteplirsen in Participants With Duchenne Muscular Dystrophy (DMD) (MIS51ON)
- Registration Number
- NCT03992430
- Lead Sponsor
- Sarepta Therapeutics, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 160
- 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.
- 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).
Other inclusion/exclusion criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1: Eteplirsen 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. Part 2: Eteplirsen 30 mg/kg Eteplirsen Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks. Part 2: Eteplirsen 200 mg/kg Eteplirsen Randomized participants will receive eteplirsen 200 mg/kg once weekly for up to 144 weeks. Part 2: Eteplirsen 100 mg/kg Eteplirsen Randomized participants will receive eteplirsen 100 mg/kg once weekly for up to 144 weeks.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression Baseline, Postdose (at Week 24, Week 48, or Week 144) Part 2: Incidence of Adverse Events (AEs) Baseline up to Week 148 Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen 0 (predose) to 2 hours postdose up to Week 144 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
Trial Locations
- Locations (59)
Royal Institute of Child Neurosciences
🇮🇳Ahmedabad, India
Charité Universitätsmedizin Berlin CVK
🇩🇪Berlin, Germany
Aster RV Hospital
🇮🇳Bengaluru, India
Nizam's Institute of Medical Sciences
🇮🇳Hyderabad, India
All India Institute of Medical Sciences
🇮🇳New Delhi, India
Christian Medical College
🇮🇳Vellore, India
IRCCS Instituto Gianna Gaslini
🇮🇹Genova, Italy
Fondazione Policlinico Universitario A. Gemelli- IRCCS
🇮🇹Rome, Italy
Radboud University Nijmegen Medical Centre
🇳🇱Nijmegen, Netherlands
University Children's Hospital
🇷🇸Belgrade, Serbia
Brno Klinika detske neurologie
🇨🇿Brno, Czechia
Rigshospitalet Copenhagen University Hospital
🇩🇰Copenhagen, Denmark
University of Florida
🇺🇸Gainesville, Florida, United States
Fakultni nemocnice v Motole
🇨🇿Praha 5, Czechia
Hospital Pablo Tobón Uribe
🇨🇴Medellin, Colombia
Jaicare Hospital (A Unit of Sarvee Integra Pvt Ltd.)
🇮🇳Madurai, India
CHRU de Strasbourg
🇫🇷Strasbourg, France
Neurociencias Estudios Clínicos S.C.
🇲🇽Culiacán, Sinaloa, Mexico
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳Pune, India
Children's Health Ireland (CHI) at Temple Street
🇮🇪Dublin 1, Ireland
The Specialty Hospital (TSH)/Advanced Clinical Center
🇯🇴Amman, Jordan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Istiklal Hosptial (IST)
🇯🇴Amman, Jordan
Irbid Specialty Hospital
🇯🇴Irbid, Jordan
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Oslo Universitetssykehus HF Rikshospitalet
🇳🇴Oslo, Norway
National Clinical Hospital for Children Neurorehabilitation "Dr. Nicolae Robănescu"
🇷🇴Bucharest, Romania
UCL Institute of Child Health Great Ormond Street
🇬🇧London, United Kingdom
Hospital Sant Joan de Deu
🇪🇸Barcelona, Spain
Hospital Universitari i Politecnic La Fe de Valencia
🇪🇸Valencia, Spain
Clinic for Neurology and Psychiatry for Children and Youth
🇷🇸Belgrade, Serbia
University Medical Centre Ljubljana
🇸🇮Ljubljana, Slovenia
Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic"
🇷🇸Belgrade, Serbia
Kaohsiung Medical University
🇨🇳Kaohsiung, Taiwan
Birmingham Heartlands Hospital
🇬🇧Birmingham, United Kingdom
Mersin University Medical Faculty
🇹🇷Mersin, Turkey
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Rare Disease Research, LLC
🇺🇸Atlanta, Georgia, United States
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, West Yorkshire, United Kingdom
IASO Children's Hospital
🇬🇷Marousi, Attiki, Greece
Sir Ganga Ram Hospital
🇮🇳New Delhi, India
Pharmaceutical Research Center/Jordan University of Science and Technology
🇯🇴Irbid, Jordan
New Zealand Clinical Research - Auckland
🇳🇿Auckland, New Zealand
Hospital Universitario San Ignacio
🇨🇴Bogotá, Colombia
Instituto Neurologico de Colombia (INDEC)
🇨🇴Medellin, Colombia
Hopital Femme Mere Enfant
🇫🇷Bron, France
Universitätsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Freiburg
🇩🇪Freiburg, Germany
Hopital Armand Trousseau
🇫🇷Paris, France
Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete
🇭🇺Budapest, Hungary
Pusan National University Yangsan Hospital
🇰🇷Yangsan, Korea, Republic of
Instituto de Investigaciones Clinicas para la Salud A.C
🇲🇽Durango, Mexico
Children's Department and Department for Children's Habilitation at Stavanger University Hospital
🇳🇴Stavanger, Norway
Klinika Neurologii Rozwojowej
🇵🇱Gdansk, Pomorskie, Poland
Akdeniz Universitesi Tip Fakultesi
🇹🇷Antalya, Turkey
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Universitätsspital Basel
🇨🇭Basel, Switzerland