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

• Register: ClinicalTrials.gov
• Last refreshed on: 22 April 2024
• Main ID: NCT03992430
• Date of registration: 18/06/2019
• Prospective Registration: Yes
• Primary sponsor: Sarepta Therapeutics, Inc.
• Public title: A Study to Compare Safety and Efficacy of a High Dose of Eteplirsen in Participants With Duchenne Muscular Dystrophy (DMD) (MIS51ON)
• Scientific 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
• Date of first enrolment: July 13, 2020
• Target sample size: 160
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03992430
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Canada, 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, United States

Contacts

• Name: Medical Director
• Affiliation: Sarepta Therapeutics, Inc.

Key inclusion & exclusion criteria

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.



Age minimum: 4 Years
Age maximum: 13 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Muscular Dystrophy, Duchenne

Intervention(s)

Drug: Eteplirsen

Primary Outcome(s)

Part 2: Change From Baseline in the NSAA Total Score at Week 144 [Time Frame: Baseline, Week 144]

Part 1: Incidence of Adverse Events (AEs) [Time Frame: Up to Week 148]

Secondary Outcome(s)

Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) [Time Frame: Baseline, Week 144]

Part 2: Incidence of Adverse Events (AEs) [Time Frame: Baseline up to Week 148]

Part 2: Time to Loss of Ambulation (LOA) [Time Frame: Baseline up to Week 144]

Part 2: Change from Baseline in Forced Vital Capacity Percent Predicted (FVC%p) at Week 144 [Time Frame: Baseline, Week 144]

Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression [Time Frame: Baseline, Postdose (at Week 24, Week 48, or 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 [Time Frame: Baseline, Week 144]

Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen [Time Frame: 0 (predose) to 2 hours postdose up to Week 144]

Secondary ID(s)

4658-402

Source(s) of Monetary Support

Please refer to primary and secondary sponsors