ATX-01 for Myotonic Dystrophy

(ArthemiR Trial)

Recruiting at 9 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ATX-01 for individuals with myotonic dystrophy type 1 (DM1), a condition that affects muscles and causes issues like muscle stiffness and weakness. The main aim is to determine if ATX-01 is safe and well-tolerated. Participants will receive either ATX-01 or a placebo to compare effects. The trial seeks individuals who can walk without devices like canes and have experienced muscle stiffness for more than three seconds. As a Phase 1, Phase 2 trial, this research focuses on understanding how ATX-01 works in people and measuring its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that ATX-01 is likely to be safe for humans?

Research shows that ATX-01 is a new treatment under development for myotonic dystrophy type 1, a condition affecting muscles and other body parts. This clinical trial aims to determine ATX-01's safety and tolerability. As a Phase 1/2 trial, it marks one of the first tests of ATX-01 in humans, so limited safety information may be available.

Reaching this phase indicates that ATX-01 has shown promise in earlier lab studies, typically involving cells or animals. The trial will closely monitor participants for any side effects, recording and studying any negative reactions.

Since ATX-01 is still in the early stages of human testing, participants should be aware that information on treatment tolerability is still being collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for myotonic dystrophy focus on managing symptoms with medications like mexiletine or physical therapy. However, ATX-01 works differently by targeting the root cause of the disease. It uses an anti-microRNA called X82108, a novel type of antisense oligonucleotide, to specifically inhibit microRNA 23b. This is exciting because it offers a new way to potentially alter the disease process itself, rather than just alleviating symptoms. Researchers are hopeful that this innovative approach could lead to more effective and long-lasting treatments for patients.

What evidence suggests that ATX-01 might be an effective treatment for myotonic dystrophy?

Research shows that ATX-01, a new treatment under study in this trial, targets a molecule called miR-23b. This molecule links to myotonic dystrophy type 1 (DM1), a condition affecting muscles and other body parts. In lab and animal studies, ATX-01 has shown promise in reducing DM1 effects by blocking miR-23b. Although human studies provide limited information, these early results suggest that ATX-01 may help manage DM1 symptoms. This treatment aims to address the disease's root cause, offering hope for an effective therapy. Participants in this trial will receive either ATX-01 or a placebo. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06300307

NCT06300307 | Study of ATX-01 in Participants With DM1 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 ...

2. neurologylive.com neurologylive.com/view/patient-dosing-commenced-phase-1-2-arthemir-trial-atx-01-myotonic-dystrophy-type-1

Patient Dosing Commenced for Phase 1/2 ArthemiR Trial ... ArthemiR, a placebo-controlled study, primarily evaluates the safety of ATX-01 in myotonic dystrophy type 1, with other assessments that include ...

3. clinicaltrials.eu clinicaltrials.eu/inn/atx-01/

Atx-01 – Application in Therapy and Current Clinical ... ATX-01 is a new drug being developed to treat Myotonic Dystrophy Type 1 (DM1), a genetic disorder that affects muscles and other body systems.

4. columbusvp.com columbusvp.com/en/arthex-biotech-receives-ind-clearance-from-fda-to-initiate-the-phase-i-iiaarthemirtm-trial-of-atx-01-for-myotonic-dystrophy-type-1-dm1/

ARTHEx Biotech Receives IND Clearance from FDA to ... The Company's lead investigational compound, ATX-01, is being evaluated for the treatment of myotonic dystrophy type 1 (DM1), a rare neuromuscular disorder, in ...

5. medicamentos-innovadores.org medicamentos-innovadores.org/sites/medicamentosinnovadores/docs/PRODF530369.pdf?blobnocache=false

ATX-01 Data from in vitro and in vivo models demonstrate that ATX-01 is efficiently ... myotonic dystrophy (including ATX-01). • Granted in US, JP and AU.

6. arthexbiotech.com arthexbiotech.com/post/arthex-biotech-announces-first-patient-dosed-in-phase-i-iia-arthemir-tm-trial-for-myotonic-dystrophy-type-1-dm1

ARTHEx Biotech Announces First Patient Dosed in Phase I ... The Company's lead investigational compound, ATX-01, is being evaluated for the treatment of myotonic dystrophy type 1 (DM1), a rare ...