Casimersen + Golodirsen for Duchenne Muscular Dystrophy

(ESSENCE Trial)

Recruiting at 75 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: Gene therapy

Disqualifiers: Major surgery, Significant illness, others

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

Duration: 96 weeks

228 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The main objective of this study is to evaluate the efficacy of SRP-4045 (casimersen) and SRP-4053 (golodirsen) compared to placebo in participants with DMD with out-of-frame deletion mutations amenable to skipping exon 45 and exon 53, respectively.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of oral corticosteroids for at least 24 weeks before starting and throughout the study. The protocol does not specify about other medications, so it's best to discuss with the trial team.

Is Casimersen + Golodirsen safe for humans?

Casimersen and Golodirsen have been studied for safety in patients with Duchenne muscular dystrophy, and adverse events were generally mild and not serious. Long-term studies of Golodirsen showed no safety-related discontinuations or deaths, suggesting it is generally safe for human use. ^{1 2 3 4 5}

How is the drug Casimersen + Golodirsen unique for treating Duchenne Muscular Dystrophy?

Casimersen and Golodirsen are unique because they are designed to target specific mutations in the DMD gene, using a method called exon skipping to help produce a functional version of the dystrophin protein, which is missing in patients with Duchenne Muscular Dystrophy. Casimersen targets exon 45, while Golodirsen targets exon 53, making them suitable for different subsets of patients based on their genetic mutations. ^{1 2 3 4 6}

What data supports the effectiveness of the drug Casimersen + Golodirsen for Duchenne Muscular Dystrophy?

Casimersen and Golodirsen are drugs designed to help produce a functional version of the dystrophin protein, which is missing in patients with Duchenne Muscular Dystrophy (DMD). Casimersen has been shown to increase dystrophin production in patients with specific genetic mutations, and Golodirsen has also demonstrated positive results in increasing dystrophin levels in clinical trials. ^{1 2 3 4 6}

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 individuals with Duchenne Muscular Dystrophy (DMD) who have specific genetic deletions treatable by skipping exon 45 or exon 53. Participants must be on a stable dose of corticosteroids, have certain muscle function, and maintain a specific range in the 6-minute walk test. They should not have had gene therapy or other recent experimental treatments.

Inclusion Criteria

I have been on a stable dose of oral corticosteroids for at least 24 weeks.

My lung function is at least half of what is expected for someone my age and size.

I can walk between 300 to 450 meters in 6 minutes.

Exclusion Criteria

I have been treated with SMT C1100 recently and PRO045, PRO053, or PRO051 in the last 6 months.

Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1

I have not had major surgery in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly IV infusions of SRP-4045 or SRP-4053 or placebo for up to 96 weeks

96 weeks

Weekly visits (in-person)

Open-label extension

All participants receive open-label active treatment of SRP-4045 or SRP-4053 for 48 weeks

48 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• SRP-4045
• SRP-4053

Trial Overview The study tests the effectiveness of two drugs, SRP-4045 (casimersen) and SRP-4053 (golodirsen), against a placebo in improving DMD symptoms related to specific genetic mutations. The goal is to see if these drugs can help skip over faulty parts of the gene.

How Is the Trial Designed?

Group I: SRP-4053 Experimental Treatment 1 Intervention

Participants amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).

Group II: SRP-4045 Experimental Treatment 1 Intervention

Participants amenable to exon 45 skipping will receive SRP-4045 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).

Group III: Placebo followed by SRP-4045 or SRP-4053 Placebo Group 3 Interventions

Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).

Who Is Running the Clinical Trial?

Sarepta Therapeutics, Inc.

Lead Sponsor

Trials

54

Recruited

34,000+

Published Research Related to This Trial

Antisense-mediated exon skipping therapy, like the newly approved casimersen (Amondys 45), offers a promising treatment for Duchenne muscular dystrophy (DMD) by restoring the reading frame of dystrophin transcripts, potentially benefiting about 8% of DMD patients.

Casimersen received accelerated FDA approval in February 2021, but its continued use will depend on positive outcomes from an ongoing phase III clinical trial, highlighting the importance of ongoing research for safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Casimersen for Duchenne muscular dystrophy. Wilton-Clark, H., Yokota, T.[2021]

Golodirsen was found to be well-tolerated in patients with Duchenne muscular dystrophy (DMD), with safety results consistent with previous studies in pediatric patients.

Treatment with golodirsen led to a significant increase in exon 53 skipping and a 16-fold increase in dystrophin protein expression at week 48, indicating its potential efficacy in restoring dystrophin production in muscle tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Frank, DE., Schnell, FJ., Akana, C., et al.[2023]

Citations

1. New Zealand pubmed.ncbi.nlm.nih.gov

Golodirsen: First Approval. [2021]

2. Spain pubmed.ncbi.nlm.nih.gov

Casimersen for Duchenne muscular dystrophy. [2021]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Casimersen: First Approval. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1/2 Trial. [2022]