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

Muscular Dystrophy, Duchenne Clinical Trial

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03992430
• Other study ID #: 4658-402
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 13, 2020
• Est. completion date: November 30, 2024

Study information

• Verified date: April 2024
• Source: Sarepta Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 13 Years

Eligibility

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.

Related Conditions & MeSH terms

• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• Eteplirsen
Solution for intravenous (IV) infusion.

Locations

Country	Name	City	State
Colombia	Hospital Universitario San Ignacio	Bogotá
Colombia	Hospital Pablo Tobón Uribe	Medellin
Colombia	Instituto Neurologico de Colombia (INDEC)	Medellin
Czechia	Brno Klinika detske neurologie	Brno
Czechia	Fakultni nemocnice v Motole	Praha 5
Denmark	Rigshospitalet Copenhagen University Hospital	Copenhagen
France	Hopital Femme Mere Enfant	Bron
France	Hopital Armand Trousseau	Paris
France	CHRU de Strasbourg	Strasbourg
Germany	Charité Universitätsmedizin Berlin CVK	Berlin
Germany	Universitätsklinikum Essen	Essen
Germany	Universitätsklinikum Freiburg	Freiburg
Greece	IASO Children's Hospital	Marousi	Attiki
Hungary	Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete	Budapest
India	Royal Institute of Child Neurosciences	Ahmedabad
India	Aster RV Hospital	Bengaluru
India	Nizam's Institute of Medical Sciences	Hyderabad
India	Jaicare Hospital (A Unit of Sarvee Integra Pvt Ltd.)	Madurai
India	All India Institute of Medical Sciences	New Delhi
India	Sir Ganga Ram Hospital	New Delhi
India	Deenanath Mangeshkar Hospital & Research Centre	Pune
India	Christian Medical College	Vellore
Ireland	Children's Health Ireland (CHI) at Temple Street	Dublin 1
Italy	IRCCS Instituto Gianna Gaslini	Genova
Italy	Fondazione Policlinico Universitario A. Gemelli- IRCCS	Rome
Jordan	Istiklal Hosptial (IST)	Amman
Jordan	The Specialty Hospital (TSH)/Advanced Clinical Center	Amman
Jordan	Irbid Specialty Hospital	Irbid
Jordan	Pharmaceutical Research Center/Jordan University of Science and Technology	Irbid
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan
Mexico	Neurociencias Estudios Clínicos S.C.	Culiacán	Sinaloa
Mexico	Instituto de Investigaciones Clinicas para la Salud A.C	Durango
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen
New Zealand	New Zealand Clinical Research - Auckland	Auckland
Norway	Oslo Universitetssykehus HF Rikshospitalet	Oslo
Norway	Children's Department and Department for Children's Habilitation at Stavanger University Hospital	Stavanger
Poland	Klinika Neurologii Rozwojowej	Gdansk	Pomorskie
Romania	National Clinical Hospital for Children Neurorehabilitation "Dr. Nicolae Robanescu"	Bucharest
Serbia	Clinic for Neurology and Psychiatry for Children and Youth	Belgrade
Serbia	Mother and Child Health Care Institute of Serbia "Dr Vukan Cupic"	Belgrade
Serbia	University Children's Hospital	Belgrade
Slovenia	University Medical Centre Ljubljana	Ljubljana
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Switzerland	Universitätsspital Basel	Basel
Taiwan	Kaohsiung Medical University	Kaohsiung
Taiwan	National Taiwan University Hospital	Taipei
Turkey	Akdeniz Universitesi Tip Fakultesi	Antalya
Turkey	Mersin University Medical Faculty	Mersin
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	West Yorkshire
United Kingdom	UCL Institute of Child Health Great Ormond Street	London
United States	Rare Disease Research, LLC	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Florida	Gainesville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sarepta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Colombia,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Ireland,  Italy,  Jordan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Norway,  Poland,  Romania,  Serbia,  Slovenia,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Incidence of Adverse Events (AEs)		Up to Week 148
Primary	Part 2: Change From Baseline in the NSAA Total Score at Week 144		Baseline, Week 144
Secondary	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
Secondary	Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT)		Baseline, Week 144
Secondary	Part 2: Change from Baseline in Forced Vital Capacity Percent Predicted (FVC%p) at Week 144		Baseline, Week 144
Secondary	Part 2: Time to Loss of Ambulation (LOA)		Baseline up to Week 144
Secondary	Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression		Baseline, Postdose (at Week 24, Week 48, or Week 144)
Secondary	Part 2: Incidence of Adverse Events (AEs)		Baseline up to Week 148
Secondary	Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen		0 (predose) to 2 hours postdose up to Week 144

External Links

•   Click here to access the website, clinicaltrials.sarepta.com/MIS51ON, for additional information for the study.