A randomized, double-blind research study on the safety and efficacy of high doses of Eteplirsen in certain patients with Duchenne muscular dystrophy

Canada, Colombia, Czechia, Denmark, France, Germany, Greece, Hungary, India, Ireland, Italy, Jordan, Mexico, Netherlands, New Zealand, Norway, Poland, Romania, Serbia, Slovenia, South Korea, Spain, Switzerland, Taiwan, Turkey (T�rkiye), United Kingdom, United States (ICTRP)

ICTRP Trial ID
NCT03992430 (ICTRP)

Official title (approved by ethics committee)
A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of High Doses of Eteplirsen, Preceded by an Open-label Dose Escalation, in Patients with Duchenne Muscular Dystrophy With Deletion Mutations Amenable to Exon 51 Skipping (BASEC)

Academic title
A Randomized, Double-Blind, Dose Finding and Comparison Study of the Safety and Efficacy of High Doses of Eteplirsen, Preceded by an Open-label Dose Escalation, in Patients With Duchenne Muscular Dystrophy With Deletion Mutations Amenable to Exon 51 Skipping (ICTRP)

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

Disease under investigation
Muscular Dystrophy, Duchenne (ICTRP)

Intervention under investigation
Drug: Eteplirsen (ICTRP)

Type of trial
Interventional (ICTRP)

Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

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
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. (ICTRP)

not available

Primary and secondary end points
Part 1: Incidence of Adverse Events (AEs);Part 2: Change From Baseline at Week 144 in the NSAA Total Score (for Final Analysis);Part 2: Change from Baseline at Week 72 or Week 96 in NSAA Total Score (for Conditional Efficacy Interim Analysis) (ICTRP)

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;Part 2: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT);Part 2: Change from Baseline at Week 144 in Forced Vital Capacity Percent Predicted (FVC%p);Part 2: Time to Loss of Ambulation (LOA);Part 2: Change From Baseline in Skeletal Muscle Dystrophin Expression;Part 2: Incidence of Adverse Events (AEs);Part 2: Pharmacokinetic (PK) Plasma Concentration of Eteplirsen (ICTRP)

Registration date
not available

Incorporation of the first participant
not available

Secondary sponsors
not available

Additional contacts
Medical Director, Sarepta Therapeutics, Inc. (ICTRP)

Secondary trial IDs
2018-001762-42, 2024-511492-15-00, 4658-402 (ICTRP)

Results-Individual Participant Data (IPD)
not available

Further information on the trial
https://clinicaltrials.gov/study/NCT03992430 (ICTRP)