High-Dose Eteplirsen for DMD

(MIS51ON Trial)

Not currently recruiting at 70 trial locations

Overseen By Sarepta Therapeutics Inc. For Clinical Trial Information, Select Option 4

Age: < 18

Sex: Male

Trial Phase: Phase 3

Sponsor: Sarepta Therapeutics, Inc.

Must be taking: Corticosteroids

Must not be taking: Antisense oligonucleotides, Gene therapy

Disqualifiers: Major surgery, Neuromuscular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests higher doses of eteplirsen, a treatment designed to slow the progression of Duchenne muscular dystrophy (DMD), a genetic disorder causing muscle weakness. It examines whether doses of 100 mg/kg and 200 mg/kg are safe and more effective than the standard 30 mg/kg dose. The trial is suitable for males diagnosed with DMD who have a specific genetic mutation treatable by skipping exon 51, can walk independently, and have been on a stable dose of corticosteroids. Researchers will monitor participants for safety and effectiveness over time. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment option.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medications other than corticosteroids for at least 12 weeks before joining. If you're on corticosteroids, you must have been on a stable dose for at least 12 weeks before starting the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that eteplirsen is generally safe for treating Duchenne muscular dystrophy (DMD). The FDA has approved it for patients who can benefit from a specific genetic treatment called exon 51 skipping. Previous studies found that eteplirsen is well-tolerated by patients, including young boys aged 6 to 48 months.

Thorough safety checks, including a study examining its long-term safety over four years, consistently show that eteplirsen is safe and well-tolerated. While some side effects can occur, data suggest they are manageable and not serious.

Prospective clinical trial participants should discuss the possible risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for DMD?

Unlike the standard treatments for Duchenne muscular dystrophy (DMD), which often focus on managing symptoms and slowing progression, eteplirsen is designed to directly target the genetic cause of the disease. Eteplirsen employs exon skipping, a technique that helps the body produce a functional version of dystrophin, the protein lacking in DMD patients. Researchers are excited because this method offers a more targeted approach, potentially leading to improved muscle function and slower disease progression compared to existing therapies. Each dose variation of eteplirsen in the trial—ranging from 30 mg/kg to 200 mg/kg—allows researchers to explore the optimal dosage for maximizing efficacy and safety.

What evidence suggests that eteplirsen might be an effective treatment for DMD?

Research has shown that eteplirsen can greatly increase the production of dystrophin, a protein that helps muscles function properly, in boys with Duchenne muscular dystrophy (DMD). One study found that patients' dystrophin levels increased to 23% of normal after 24 weeks. In this trial, different doses are being tested: participants in Part 1 will receive 100 mg/kg and 200 mg/kg doses, while Part 2 includes a comparison of 30 mg/kg, 100 mg/kg, and 200 mg/kg doses. The usual dose of 30 mg/kg has demonstrated positive effects over a longer period, suggesting that higher doses might be even more beneficial. Overall, eteplirsen shows promise in helping DMD patients by boosting dystrophin production. ^{2 6 7 8 9}

Who Is on the Research Team?

Medical Director

Principal Investigator

Sarepta Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for boys with Duchenne Muscular Dystrophy who can walk independently and perform a timed test quickly. They must have specific genetic mutations treatable by skipping exon 51, stable breathing function, and be on steady corticosteroid doses. Boys using other DMD treatments or with kidney issues, recent major surgery, heart problems, or other serious diseases cannot join.

Inclusion Criteria

I am between 4 to 6 years old and do not need a ventilator.

I have been on a consistent dose of oral corticosteroids for the last 12 weeks.

I can walk and complete a specific physical task in 10 seconds or less.

Exclusion Criteria

I have kidney problems or other serious health issues.

My heart's pumping ability is reduced, or my heart rhythm test shows a delay.

I have not used experimental drugs for DMD, except certain ones recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive eteplirsen 100 mg/kg once weekly for at least 4 weeks, followed by 200 mg/kg once weekly for at least 4 weeks to evaluate safety and tolerability

8 weeks

Dose Finding and Comparison

Participants receive either 30 mg/kg, 100 mg/kg, or 200 mg/kg of eteplirsen once weekly to evaluate efficacy and safety

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Eteplirsen

Trial Overview

The study tests two high doses of Eteplirsen (100 mg/kg and 200 mg/kg) against a standard dose (30 mg/kg) in boys with Duchenne Muscular Dystrophy. It's divided into two parts: first to see if the high doses are safe and then to find out which one works best compared to the standard dose.

How Is the Trial Designed?

Group I: Part 2: Eteplirsen 200 mg/kg Experimental Treatment 1 Intervention

Randomized participants will receive eteplirsen 200 mg/kg once weekly for up to 144 weeks.

Group II: Part 2: Eteplirsen 100 mg/kg Experimental Treatment 1 Intervention

Randomized participants will receive eteplirsen 100 mg/kg once weekly for up to 144 weeks.

Group III: Part 1: Eteplirsen Experimental Treatment 1 Intervention

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.

Group IV: Part 2: Eteplirsen 30 mg/kg Active Control 1 Intervention

Randomized participants will receive eteplirsen 30 mg/kg once weekly for up to 144 weeks.

Who Is Running the Clinical Trial?

Sarepta Therapeutics, Inc.

Lead Sponsor

Trials

54

Recruited

34,000+

Published Research Related to This Trial

Eteplirsen (Exondys 51) has received accelerated FDA approval as a treatment for Duchenne muscular dystrophy (DMD) by promoting dystrophin production through exon skipping, specifically targeting exon 51, which is relevant for about 14% of DMD patients.

The review highlights the pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials, while also addressing concerns regarding the drug's efficacy and its role as a potential therapeutic strategy for DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eteplirsen in the treatment of Duchenne muscular dystrophy. Lim, KR., Maruyama, R., Yokota, T.[2022]

Eteplirsen significantly increased dystrophin production in boys with Duchenne muscular dystrophy (DMD) after 24 weeks of treatment, with 23% of normal dystrophin levels observed in the 30 mg/kg group, and even higher levels (52% and 43%) at 48 weeks for the 30 and 50 mg/kg groups, respectively.

The treatment also improved walking distance on the 6-minute walk test (6MWT) by an average of 67.3 meters compared to placebo, indicating that longer treatment duration is more important for efficacy than the dosage, and no severe adverse events were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eteplirsen for the treatment of Duchenne muscular dystrophy. Mendell, JR., Rodino-Klapac, LR., Sahenk, Z., et al.[2022]

Citations

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pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/34120909/

Open-Label Evaluation of Eteplirsen in Patients with ...

ConclusionsThis large, multicenter study contributes to the growing body of evidence for eteplirsen, confirming a positive treatment effect, favorable safety ...

2.

icer.org

icer.org/wp-content/uploads/2020/10/Corrected_ICER_DMD-Final-Report_042222.pdf

Deflazacort, Eteplirsen, and Golodirsen for Duchenne ...

all treated for an additional four years with eteplirsen 30 mg/kg or 50 mg/kg.30,34,35 After 180 weeks, 11 of the 12 patients underwent muscle biopsy to ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02255552

NCT02255552 | Study of Eteplirsen in DMD Patients

This is an open-label, multi-center study to evaluate the efficacy and safety of eteplirsen in patients with genotypically confirmed Duchenne muscular dystrophy ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S0960896623000743

Safety, tolerability and pharmacokinetics of eteplirsen in ...

Results of this phase 2 study provide evidence of the safety and tolerability of weekly eteplirsen 30 mg/kg infusions in boys with DMD as young as 6 months of ...

5.

jmcp.org

jmcp.org/doi/10.18553/jmcp.2020.26.4.361

The Effectiveness and Value of Deflazacort and Exon ...

Functional outcome reported in the eteplirsen trial showed that patients on 30 mg/kg of eteplirsen experienced a greater loss of distance walked in a 6 ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/206488s035lbl.pdf

Reference ID: 5503515 - accessdata.fda.gov

EXONDYS 51 is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01540409

NCT01540409 | Efficacy, Safety, and Tolerability Rollover ...

The primary objective of this study is to assess the ongoing efficacy, safety, and tolerability of an additional 212 weeks of treatment with eteplirsen ...

8.

investorrelations.sarepta.com

investorrelations.sarepta.com/static-files/cc41f38c-47d1-4f0b-8807-56b7874b48fb

These data support the safety and tolerability of eteplirsen in ...

Safety, Tolerability, and Pharmacokinetics of Eteplirsen in Patients 6–48 Months Old With Duchenne Muscular Dystrophy. Amenable to Exon 51 ...

9.

parentprojectmd.org

parentprojectmd.org/drug-development-pipeline/exondys-51/

EXONDYS 51® - Parent Project Muscular Dystrophy

A Study to Compare Safety and Efficacy of a High Dose of Eteplirsen in Duchenne Muscular Dystrophy (DMD) Patients (MIS51ON). Media Library. JUNE 2019. Sarepta ...