EDG-5506 for Becker Muscular Dystrophy

(ARCH Trial)

Overseen By Edgewise Therapeutics

Age: 18 - 65

Sex: Male

Trial Phase: Phase 1

Sponsor: Edgewise Therapeutics, Inc.

Must not be taking: CYP3A4 inhibitors, Corticosteroids

Disqualifiers: Suicidal ideation, Psychiatric condition, others

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

Compensation: Varies

Number of Visits: 12

Duration: 24 months

12 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain drugs like moderate or strong CYP3A4 inhibitors or inducers. If you're on oral corticosteroids, you must not have taken more than 5 mg per day for over 5 days in the past 6 months.

Is EDG-5506 safe for humans?

There is no specific safety data available for EDG-5506, but a similar drug, Edasalonexent (CAT-1004), was tested in humans and found to be generally safe and well tolerated, with mild side effects like diarrhea and headache. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new drug called sevasemten to see if it can help people with Becker muscular dystrophy, a disease that weakens muscles. The drug aims to protect and improve muscle function. Participants will take the drug for an extended period with frequent check-ups to monitor safety and effectiveness.

Research Team

Sam Collins, MBBS, PhD

Principal Investigator

Edgewise Therapeutics, Inc.

Eligibility Criteria

This trial is for adult males aged 18-55 with Becker Muscular Dystrophy who can walk at least 100 meters. They must have completed a prior EDG-5506 study, weigh over 50 kg, and have a BMI of 20-34 kg/m2. Those on recent investigational drugs, with certain medical conditions or taking high doses of corticosteroids are excluded.

Inclusion Criteria

I can walk 100 meters by myself or with help.

Participants who have completed Study EDG-5506-001

Body mass index (BMI) between 20 and 34 kg/m2 inclusive

Exclusion Criteria

Medical history or other medical or psychiatric condition including recent or active suicidal ideation/behavior or laboratory result or abnormality that may increase the risk of study participation or, in the Investigator's judgment, make the participant inappropriate for the study. Includes venous access that would be too difficult to facilitate repeated blood sampling.

I am taking medication that strongly affects liver enzymes.

I have taken high-dose oral steroids for more than 5 days in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sevasemten to assess safety and pharmacokinetics

24 months

Monthly visits for the first 12 months, then every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• EDG-5506

Trial Overview The ARCH study is testing EDG-5506 in adults with Becker muscular dystrophy to see if it's safe and how the body processes it. It aims to protect and improve muscle function in patients by administering this experimental drug in an open-label, single-center Phase 1b setting.

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]