PGN-EDODM1 for Myotonic Dystrophy

(FREEDOM-DM1 Trial)

Recruiting in Palo Alto (17 mi)

+12 other locations

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: PepGen Inc

Must not be taking: Myotonia medications

Disqualifiers: Congenital DM1, Abnormal labs, others

Trial Summary

What is the purpose of this trial?

This trial is testing the safety and tolerability of a drug called PGN-EDODM1, given through an IV, in people with Myotonic Dystrophy Type 1 (DM1). The drug aims to address the underlying issues causing muscle problems in these patients. The study includes initial assessments followed by a period of receiving the drug and monitoring.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications specifically for the treatment of myotonia at least 2 weeks before the screening period.

What data supports the effectiveness of the drug PGN-EDODM1 for Myotonic Dystrophy?

Research on similar treatments, like antisense oligonucleotides (ASOs), shows they can improve muscle issues in myotonic dystrophy by targeting specific genetic problems. Combining ASO treatment with exercise has been shown to reduce fatigue in mice with myotonic dystrophy, suggesting potential benefits for similar therapies. ^{1 2 3 4 5}

How is the drug PGN-EDODM1 different from other drugs for myotonic dystrophy type 1?

PGN-EDODM1 is unique because it is part of a new wave of treatments exploring nucleic acid-based therapies, which aim to target the underlying genetic causes of myotonic dystrophy type 1, unlike traditional drugs like mexiletine that focus on symptom relief. ^{2 6 7 8 9}

Research Team

Eligibility Criteria

This trial is for individuals with Myotonic Dystrophy Type 1. Participants must be adults who meet specific health criteria during the screening period, which lasts up to 30 days before starting treatment.

Inclusion Criteria

My leg muscles are strong enough to move against some resistance.

I experience muscle stiffness that doesn't relax quickly.

I have been diagnosed with DM1 due to a specific genetic marker.

Exclusion Criteria

I was born with myotonic dystrophy type 1.

Known history or presence of any clinically significant conditions that may interfere with study safety assessments

Percent predicted forced vital capacity (FVC) <40%

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment and Observation

Participants receive single intravenous (IV) doses of PGN-EDODM1 or placebo and are observed for safety and tolerability

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PGN-EDODM1 (Other)
• Placebo (Other)

Trial Overview The study tests the safety and tolerability of a new drug called PGN-EDODM1 given through an IV compared to a placebo in people with Myotonic Dystrophy Type 1 over a period of 16 weeks.

Participant Groups

Group I: PGN-EDODM1 Experimental Treatment 1 Intervention

PGN-EDODM1 for infusion

Group II: Placebo Placebo Group 1 Intervention

0.9% NaCl

Who Is Running the Clinical Trial?

PepGen Inc

Lead Sponsor

Trials

4

Recruited

80+

Findings from Research

In a randomized trial involving 42 adult patients with myotonic dystrophy type 1, mexiletine did not improve the 6-minute walk distance after 6 months, indicating no significant impact on overall mobility.

However, mexiletine did show a positive effect on hand grip myotonia, suggesting it may help with muscle stiffness, while safety assessments revealed no significant differences in adverse events or cardiac conduction between mexiletine and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial. Heatwole, C., Luebbe, E., Rosero, S., et al.[2021]

In a study of 46 patients with myotonic dystrophy type 1 (DM1), the Muscular Impairment Rating Scale (MIRS) showed significant correlations with myopathological changes, particularly in nuclear translocation and ragged red fibers, indicating that MIRS can reflect underlying muscle pathology.

The findings suggest that while MIRS is associated with certain myopathological features, it does not correlate with all aspects of muscle fiber changes, such as connective tissue proliferation, highlighting its specific utility in assessing DM1 severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Correlation of muscular impairment rating scale with myopathological changes in myotonic dystrophy type 1]. Wang, W., Liu, Q., Wang, ZX., et al.[2014]

A nationwide registry for myotonic dystrophies (DM) in Japan has successfully enrolled 976 patients, primarily with DM1, providing a crucial resource for future clinical trials and therapeutic development.

The study found that longer CTG repeat lengths in DM1 patients are associated with earlier disease onset and significantly influence clinical outcomes like grip strength and lung function, highlighting the importance of genetic factors in disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of myotonic dystrophy patients in the national registry of Japan. Sugimoto, M., Kuru, S., Takada, H., et al.[2022]

The HandClench Relaxometer (HCR) is a new, portable device that effectively measures grip myotonia and strength in individuals with myotonic dystrophy type 1 (DM1), showing excellent reliability and sensitivity compared to traditional methods.

In a study involving 20 DM1 patients and 10 controls, the HCR demonstrated the ability to detect myotonia in milder cases and correlated well with other strength and dexterity measures, making it a promising tool for clinical trials and research in DM1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simple and economical HandClench Relaxometer device for reliable and sensitive measurement of grip myotonia in myotonic dystrophy. Bulea, TC., Guth, A., Sarkar, N., et al.[2022]

Mexiletine, at doses of 150 mg and 200 mg taken three times daily, significantly reduced grip relaxation time in patients with myotonic dystrophy type 1 (DM1), indicating its effectiveness in treating myotonia.

The treatment was found to be safe, with no serious adverse events reported and no significant changes in heart rhythm, making it a well-tolerated option for managing symptoms of DM1 over a 7-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. Logigian, EL., Martens, WB., Moxley, RT., et al.[2022]

Myotonic dystrophy type 1 (DM1) affects at least half a million people and has various therapeutic approaches currently under development, with nearly two dozen drugs being explored.

Among these, the repurposed drugs tideglusib, mexiletine, and metformin show the most promise for potential marketing authorization, with eight therapies already in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myotonic dystrophy type 1 drug development: A pipeline toward the market. Pascual-Gilabert, M., López-Castel, A., Artero, R.[2022]

There is a growing pipeline of nearly 20 candidate drugs for myotonic dystrophy type 1 (DM1), with three first-in-human clinical trials currently underway, including nucleic acid therapies AOC 1001 and DYNE-101, and the small molecule pitolisant.

Promising preclinical data for additional nucleic-acid therapies and a CRISPR-based approach suggest an increasing likelihood of successful treatments for DM1, alongside repurposed drugs like tideglusib and metformin already in clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The myotonic dystrophy type 1 drug development pipeline: 2022 edition. Pascual-Gilabert, M., Artero, R., López-Castel, A.[2023]

A new mouse model with mutations in multiple genes (Dmpk, Six5, Mbnl1, and Dmwd) was developed to mimic the genetic changes seen in myotonic dystrophy type 1 (DM1), showing adult-onset DM1 symptoms.

The study indicates that the diverse symptoms of DM1 are likely caused by reduced gene dosage across several genes, and the models created can be used to test potential treatments for the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1. Yin, Q., Wang, H., Li, N., et al.[2021]

References

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

Mexiletine in Myotonic Dystrophy Type 1: A Randomized, Double-Blind, Placebo-Controlled Trial. [2021]

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

Antisense oligonucleotide and adjuvant exercise therapy reverse fatigue in old mice with myotonic dystrophy. [2021]

3. China pubmed.ncbi.nlm.nih.gov

[Correlation of muscular impairment rating scale with myopathological changes in myotonic dystrophy type 1]. [2014]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Characteristics of myotonic dystrophy patients in the national registry of Japan. [2022]

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

Simple and economical HandClench Relaxometer device for reliable and sensitive measurement of grip myotonia in myotonic dystrophy. [2022]

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

Mexiletine is an effective antimyotonia treatment in myotonic dystrophy type 1. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Myotonic dystrophy type 1 drug development: A pipeline toward the market. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The myotonic dystrophy type 1 drug development pipeline: 2022 edition. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Dosage effect of multiple genes accounts for multisystem disorder of myotonic dystrophy type 1. [2021]