EDG-5506 for Becker Muscular Dystrophy

(MESA Trial)

Recruiting at 40 trial locations

Age: Any Age

Sex: Male

Trial Phase: Phase 2

Sponsor: Edgewise Therapeutics, Inc.

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers, corticosteroids

Disqualifiers: Significant changes, investigational drugs, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Long-term

260 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take certain drugs that affect liver enzymes (cytochrome P450 CYP3A4 inhibitors or inducers) or oral corticosteroids for BMD. If you're on these, you might need to stop or switch.

Is EDG-5506 safe for humans?

There is no specific safety data available for EDG-5506, but a similar drug, Edasalonexent (CAT-1004), was well tolerated in human studies, with mild diarrhea and headache being the most common side effects. ^{1 2 3 4 5}

What is the purpose of this trial?

EDG-5506-203 MESA is an open-label extension study to assess the long-term effect of sevasemten (EDG-5506) on safety, biomarkers, and functional measures in adults and adolescents with Becker muscular dystrophy

Research Team

Roxana D. Dreghici, MD

Principal Investigator

Edgewise Therapeutics, Inc.

Joanne M. Donovan, MD, PhD

Principal Investigator

Edgewise Therapeutics, Inc.

Eligibility Criteria

This trial is for adults and adolescents with Becker muscular dystrophy who have completed certain prior studies (EDG-5506-002 ARCH, EDG-5506-201 CANYON and GRAND CANYON, or EDG-5506-202 DUNE) without significant safety concerns. They must not have taken any investigational drugs other than EDG-5506 recently or oral corticosteroids in the past 6 months.

Inclusion Criteria

You have participated in certain previous studies and completed all the required visits.

For EDG-5506-002 ARCH: Completion of the final study Visit 27 [Month 24]; or, completion of the ET visit prior to Visit 27 [Month 24]

I have completed at least 36 weeks of a specific treatment.

Exclusion Criteria

I have taken oral steroids for bone marrow disease in the last 6 months.

Any clinically significant changes during or following participation in specific prior studies that would affect the potential safety of the participant to receive EDG-5506

I haven't taken any experimental drugs recently, except EDG-5506.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive long-term dosing of sevasemten to evaluate safety, tolerability, and durability of effect

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• EDG-5506

Trial Overview The study tests the long-term effects of a drug called EDG-5506 on safety, biomarkers, and functional measures in participants with Becker muscular dystrophy. It's an open-label extension meaning everyone knows they are getting the actual drug without any placebo control.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Drug: Sevasemten

Who Is Running the Clinical Trial?

Edgewise Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,000+

Medpace, Inc.

Industry Sponsor

Trials

98

Recruited

30,400+

Dr. August J. Troendle

Medpace, Inc.

Chief Executive Officer since 1992

MD from the University of Maryland, School of Medicine; MBA from Boston University

Dr. Reinilde Heyrman

Medpace, Inc.

Chief Medical Officer since 2017

MD

Findings from Research

In a phase 3 study involving 131 children aged 4 to under 8 years with Duchenne muscular dystrophy, edasalonexent was generally well-tolerated and had a manageable safety profile, with most side effects being mild gastrointestinal issues like diarrhea.

While edasalonexent did not show statistically significant improvements in overall muscle function compared to placebo, younger patients (6 years or younger) demonstrated more promising results, suggesting that early treatment may help slow disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial. Finkel, RS., McDonald, CM., Lee Sweeney, H., et al.[2021]

The bmx mouse model, created using CRISPR/Cas9 technology, successfully mimics Becker muscular dystrophy (BMD) by expressing a common mutation in the dystrophin gene, allowing for the study of muscle and heart dysfunction associated with the disease.

This model shows significant muscle weakness and heart dysfunction compared to wild-type mice, with increased muscle damage and inflammation, making it a valuable tool for understanding BMD and testing potential therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The X-linked Becker muscular dystrophy (bmx) mouse models Becker muscular dystrophy via deletion of murine dystrophin exons 45-47. Heier, CR., McCormack, NM., Tully, CB., et al.[2023]

In a phase 3 study involving 79 patients aged 7-16 with Duchenne muscular dystrophy, eteplirsen treatment for 96 weeks resulted in a significant increase in dystrophin production (7-fold) and exon skipping (18.7-fold), indicating its efficacy in addressing the underlying cause of the disease.

The study also demonstrated a favorable safety profile, with most adverse events being mild to moderate and unrelated to the treatment, while showing a notable slowing of disease progression compared to untreated controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. McDonald, CM., Shieh, PB., Abdel-Hamid, HZ., et al.[2022]

Edasalonexent (CAT-1004) is a promising treatment for Duchenne muscular dystrophy (DMD) that works by inhibiting the NF-κB pathway, which is linked to inflammation and muscle degeneration, showing significant effects in reducing NF-κB activity in a study with 79 adult participants.

The treatment was found to be safe and well tolerated, with mild side effects like diarrhea and headache, indicating its potential for therapeutic use in DMD and other diseases related to NF-κB activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Novel NF-κB Inhibitor, Edasalonexent (CAT-1004), in Development as a Disease-Modifying Treatment for Patients With Duchenne Muscular Dystrophy: Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics in Adult Subjects. Donovan, JM., Zimmer, M., Offman, E., et al.[2018]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

The X-linked Becker muscular dystrophy (bmx) mouse models Becker muscular dystrophy via deletion of murine dystrophin exons 45-47. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Study of dystrophin gene non-deletion/duplication mutations causing Becker muscular dystrophy]. [2012]

5. England pubmed.ncbi.nlm.nih.gov

A Novel NF-κB Inhibitor, Edasalonexent (CAT-1004), in Development as a Disease-Modifying Treatment for Patients With Duchenne Muscular Dystrophy: Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics in Adult Subjects. [2018]