ATX-01 for Myotonic Dystrophy

(ArthemiR Trial)

Recruiting at 8 trial locations

Overseen By Project Manager

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ARTHEx Biotech S.L.

Must not be taking: Mexiletine, others

Disqualifiers: Congenital DM1, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

56 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test ATX-01 in participants with myotonic dystrophy type 1 (DM1). The main question it aims to answer is if ATX-01 is safe and well tolerated. The trial will compare the safety and tolerability of ATX-01 and a matching placebo. There will be a single-ascending dose part of the trial and a multiple-ascending dose part. In the single-ascending dose, participants will receive one dose of ATX-01 or placebo. In the multiple-ascending dose part, participants will receive three doses of ATX-01 or placebo. ATX-01 is a novel anti-miR (synthetic single stranded oligonucleotide) that inhibits a microRNA called miR-23b.

Will I have to stop taking my current medications?

The trial requires that you stop using mexiletine or any other medication for myotonia at least 21 days before screening.

How is the drug ATX-01 different from other treatments for myotonic dystrophy?

ATX-01 is a novel treatment being explored for myotonic dystrophy, a condition with limited existing therapies. Unlike other treatments, ATX-01 may offer a new approach, potentially involving unique mechanisms or formulations, as current options like tideglusib, mexiletine, or metformin are repurposed drugs. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for people with myotonic dystrophy type 1 (DM1) who can walk 10 meters without help (except ankle-foot braces), have a specific genetic marker in their blood, and experience grip myotonia lasting more than three seconds.

Inclusion Criteria

I can walk 10 meters without help, except for ankle-foot braces.

Presence for >3 seconds of grip myotonia as confirmed by a central reader

I have been diagnosed with DM1, confirmed by a specific genetic test.

Exclusion Criteria

I was born with myotonic dystrophy type 1.

I cannot move my ankle upwards well or have severe muscle loss in the front of my lower leg.

I haven't taken mexiletine or similar drugs for myotonia in the last 21 days or 5 half-lives, whichever is longer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Single-Ascending Dose

Participants receive one dose of ATX-01 or placebo

1 week

Multiple-Ascending Dose

Participants receive three doses of ATX-01 or placebo

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Treatment Details

Interventions

• ATX-01

Trial Overview The study tests ATX-01, an experimental drug designed to inhibit a microRNA linked to DM1. Participants will receive either one dose of ATX-01 or placebo in the first part, followed by three doses in the second part.

Participant Groups

Group I: ATX-01 Experimental Treatment 1 Intervention

ATX-01 is a formulation of the anti-microRNA 23b (anti-miR-23b), known as X82108, a novel type of antisense oligonucleotide

Group II: Placebo Placebo Group 1 Intervention

Placebo to ATX-01

ATX-01 is already approved in United States, European Union for the following indications:

Approved in United States as ATX-01 for:

• None approved; Orphan Drug Designation for Myotonic Dystrophy Type 1 (DM1)

Approved in European Union as ATX-01 for:

• None approved; Orphan Drug Designation for Myotonic Dystrophy Type 1 (DM1)

Who Is Running the Clinical Trial?

ARTHEx Biotech S.L.

Lead Sponsor

Trials

1

Recruited

60+

Findings from Research

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]

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]

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 study involving 200 adults with myotonic dystrophy type 1 (DM1) identified upper extremity strength, particularly grip and lateral pinch strength, as strong indicators of difficulties in household activities, which can guide rehabilitation needs.

Specific cut-off scores for lateral pinch strength (4.8 kg) were established, showing good sensitivity and specificity, which can help health professionals determine when to refer DM1 patients for rehabilitation services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing upper extremity capacity as a potential indicator of needs related to household activities for rehabilitation services in people with myotonic dystrophy type 1. Raymond, K., Auger, LP., Cormier, MF., et al.[2015]

In a study of 70 adults with myotonic dystrophy type 1 (DM1), significant impairments were observed, with over 75% experiencing muscle impairments and 40% facing issues like cardiac dysfunction and low physical activity.

The study highlighted that 16% of participants were dependent on help for personal daily activities, and 52% faced restrictions in social participation, indicating a strong correlation between disease progression and limitations in daily functioning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functioning and disability in adults with myotonic dystrophy type 1. Kierkegaard, M., Harms-Ringdahl, K., Holmqvist, LW., et al.[2015]

References

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

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

2. China pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Assessing upper extremity capacity as a potential indicator of needs related to household activities for rehabilitation services in people with myotonic dystrophy type 1. [2015]

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

Functioning and disability in adults with myotonic dystrophy type 1. [2015]