PGN-EDODM1 for Myotonic Dystrophy

(FREEDOM-DM1 Trial)

Not currently recruiting at 12 trial locations

Overseen By PepGen

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: PepGen Inc

Must not be taking: Myotonia medications

Disqualifiers: Congenital DM1, Abnormal labs, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and side effects of a new treatment called PGN-EDODM1 for individuals with Myotonic Dystrophy Type 1 (DM1), a condition that causes muscle weakness and stiffness. Participants will receive either the treatment or a placebo (a saltwater solution with no active drug) through an IV. The study will help researchers determine if PGN-EDODM1 is safe and tolerable for future use. Individuals with a confirmed DM1 diagnosis, a specific genetic marker, and muscle stiffness might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how PGN-EDODM1 works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that PGN-EDODM1 is being tested for safety in people with Myotonic Dystrophy Type 1 (DM1). So far, patients have tolerated single doses of PGN-EDODM1 administered through an IV without severe side effects.

Early results suggest that the treatment's effects depend on the dose, indicating that different drug amounts might cause varying reactions in the body. Specific side effects have not been highlighted yet, suggesting that severe reactions might be rare.

At this early study stage, the main goal is to ensure the drug's safety for humans. Researchers are closely monitoring for any unwanted symptoms. The study's current stage suggests that PGN-EDODM1 has not shown major safety concerns so far. However, further studies are needed to confirm these findings. ^{1 2 3 4 5}

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

Unlike the standard treatments for myotonic dystrophy, such as mexiletine or physical therapy, PGN-EDODM1 offers a new approach by targeting the genetic root of the condition. It uses a unique mechanism called exon skipping to modify the expression of specific genes involved in the disease. This method has the potential to address the underlying cause rather than just alleviating symptoms, which is why researchers are optimistic about its impact.

What evidence suggests that PGN-EDODM1 might be an effective treatment for Myotonic Dystrophy?

Research has shown that PGN-EDODM1, which participants in this trial may receive, could aid in treating Myotonic Dystrophy Type 1 (DM1). In earlier studies, a single dose of PGN-EDODM1 improved a key cell process by 53.7%, crucial for proper cell function. Another study found a 29.1% improvement with a lower dose, suggesting potential effectiveness. Early results indicate that higher doses of PGN-EDODM1 yield better outcomes. Preclinical studies also demonstrated its ability to reduce harmful clumps in cells, common in DM1. Overall, these findings suggest that PGN-EDODM1 might be a promising treatment for individuals with DM1. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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%

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• PGN-EDODM1
• Placebo

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

In mouse models of myotonic dystrophy type 1 (DM1), targeted antisense oligonucleotide (ASO) therapies can correct molecular defects but do not fully alleviate exercise-induced fatigue, which worsens with age.

Combining ASO treatment with a moderate-intensity exercise regimen significantly reverses fatigue in older DM1 mice, suggesting that exercise is an important complement to molecular therapies for improving fatigue symptoms in DM1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antisense oligonucleotide and adjuvant exercise therapy reverse fatigue in old mice with myotonic dystrophy. Hu, N., Kim, E., Antoury, L., 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]

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]

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]

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]

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]

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]

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]

Citations

1. investors.pepgen.com investors.pepgen.com/news-releases/news-release-details/pepgen-announces-highest-mean-splicing-correction-reported-dm1

PepGen Announces Highest Mean Splicing Correction ... 53.7% mean splicing correction observed following a single 15 mg/kg dose of PGN-EDODM1, with all patients showing an improvement in splicing ...

2. investors.pepgen.com investors.pepgen.com/news-releases/news-release-details/pepgen-announces-positive-initial-results-including-robust

PepGen Announces Positive Initial Results, Including ... Significant mean splicing correction of 29.1% following a single dose of PGN-EDODM1 at 10 mg/kg –. – PGN-EDODM1 observed to have favorable ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06204809

Safety, Tolerability, PK, and PD Study of PGN-EDODM1 in ... The primary purpose of the study is to evaluate the safety and tolerability of single intravenous (IV) doses of PGN-EDODM1 administered to participants with ...

4. neurologylive.com neurologylive.com/view/early-phase-1-trial-data-suggests-therapeutic-potential-pgn-edodm1-myotonic-dystrophy-type-1

Early Phase 1 Trial Data Suggests Therapeutic Potential ... Initial data reported from the FREEDOM-DM1 trial suggest PGN-EDODM1 has dose-dependent effects in patients with DM1, with further results from study cohorts ...

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000203804

PGN-EDODM1: Preclinical Data Supporting the ... Conclusions: These preclinical studies demonstrate that PGN-EDODM1 reduced nuclear RNA foci and corrected mis-splicing at clinically relevant, tolerable doses ...

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000203993

Design of a Phase 1, Placebo-Controlled Study to Assess ... The primary objective of this single-ascending dose (SAD) study is to evaluate the safety and tolerability of PGN-EDODM1 in adults living with DM1.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960896624007090

461P Evaluation of PGN-EDODM1: FREEDOM-DM1 and ... The objective of the study is to evaluate safety and tolerability (primary objective) and plasma pharmacokinetics (secondary objective) following a single dose ...