Tideglusib for Myotonic Dystrophy

(REACH CDM X Trial)

Recruiting at 10 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: AMO Pharma Limited

Must not be taking: Strong CYP3A4 inhibitors

Disqualifiers: BMI <13.5 or >40, Neurological, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

76 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests tideglusib, a medication, in children and adolescents with Congenital or Childhood Onset Myotonic Dystrophy. It aims to improve muscle function by targeting specific body processes. The study includes both those who participated in a previous study and those who have not been treated before.

Will I have to stop taking my current medications?

The trial requires that you do not start new medications or change your current ones within 4 weeks before joining. You also cannot use certain strong medications that affect liver enzymes (like clarithromycin or ketoconazole) during this time.

How is the drug Tideglusib unique in treating myotonic dystrophy?

Tideglusib is unique because it targets glycogen synthase kinase 3β (GSK3β), which is elevated in myotonic dystrophy, helping to correct the misregulated RNA-binding proteins and reduce mutant RNA levels. This approach not only addresses the underlying genetic issues but also improves symptoms and survival in animal models, setting it apart from other treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Tideglusib for treating myotonic dystrophy type 1?

Tideglusib is being repurposed as a potential treatment for myotonic dystrophy type 1 (DM1) and is currently in clinical evaluation, showing promise alongside other drugs like mexiletine and metformin. It is one of the therapies with the most potential to receive marketing authorization for DM1, indicating its potential effectiveness. ^{1 3 6 7 8}

Who Is on the Research Team?

Harriet Gray-Stephens, BM BCh, MA (Oxon), MFPM

Principal Investigator

AMO Pharma

Are You a Good Fit for This Trial?

This trial is for individuals aged 6 to 45 with Congenital or Childhood Onset Myotonic Dystrophy, who can follow food intake rules and have a caregiver's support. It's open to those who completed the AMO-02-MD-2-003 study or are treatment naïve. Participants need confirmed genetic diagnosis and a CGI-S score of ≥3.

Inclusion Criteria

Subjects who have completed the antecedent AMO-02-MD-2-003 study through V11

I was diagnosed with DM1 as a child or it is a congenital condition.

Subjects must have a Clinical Global Impression - Severity (CGI-S) score of 3 or greater at Screening (V-1)

Exclusion Criteria

I haven't taken strong medication like ketoconazole in the last 4 weeks.

I haven't started or changed any medications in the last 4 weeks.

Hypersensitivity to tideglusib or any components of its formulation including allergy to strawberry

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weight-adjusted 1000 mg tideglusib, orally, once daily

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Optional Extended Access

Participants may opt into continuation of treatment long-term

Up to 80 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tideglusib

Trial Overview The trial tests Tideglusib's safety and effectiveness in treating Myotonic Dystrophy. It includes people from an earlier study on the same drug as well as new participants, all receiving Tideglusib in an open-label phase 2/3 setting.

How Is the Trial Designed?

Group I: Tideglusib Experimental Treatment 1 Intervention

Weight adjusted or weight banded tideglusib, orally, once daily

Who Is Running the Clinical Trial?

AMO Pharma Limited

Lead Sponsor

Trials

3

Recruited

150+

Published Research Related to This Trial

In a 9-year study of 113 adults with myotonic dystrophy type 1, performance-based measures like the Timed Up and Go test and Berg Balance Scale effectively captured changes in mobility, balance, and muscle strength, aligning with patient-reported outcomes.

While most measures showed promising responsiveness, grip strength and manual dexterity assessments were less responsive, highlighting the importance of understanding measurement errors when interpreting long-term changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Responsiveness of performance-based outcome measures for mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1. Kierkegaard, M., Petitclerc, É., Hébert, LJ., et al.[2019]

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]

In a study of 120 individuals with myotonic dystrophy type 1 (DM1), targeted sleep therapies were beneficial for 29% of participants, highlighting the importance of addressing sleep-related issues in this population.

The study identified various causes of daytime sleepiness in DM1, including obstructive sleep apnea (OSA) and respiratory failure, with treatments like CPAP and non-invasive ventilation showing mixed results in terms of patient tolerance and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleepiness and Sleep-related Breathing Disorders in Myotonic Dystrophy and Responses to Treatment: A Prospective Cohort Study. West, SD., Lochmüller, H., Hughes, J., et al.[2018]

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]

In a study of 278 adults with myotonic dystrophy type 1 (DM1), the most prevalent symptoms reported were issues with hands or arms (93.5%), fatigue (90.8%), myotonia (90.3%), and impaired sleep or daytime sleepiness (87.9%).

Fatigue and mobility limitations were identified as the most impactful symptoms on patients' lives, with significant associations found between symptom prevalence and patient age as well as CTG repeat length.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1). Heatwole, C., Bode, R., Johnson, N., et al.[2022]

In a study of patients with myotonic dystrophy types 1 (DM1) and 2 (DM2), gastrointestinal (GI) issues were prevalent, with 55% of DM1 patients reporting swallowing difficulties and 53% of DM2 patients experiencing constipation at baseline.

Over a 5-year period, GI symptoms persisted, with new cases of swallowing problems in DM1 and constipation in DM2, highlighting the need for further research into how factors like body mass index and disease duration influence these symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2. Hilbert, JE., Barohn, RJ., Clemens, PR., et al.[2023]

An RNA-targeted agent shows promise for treating myotonic dystrophy type 1 (DM1) by effectively inhibiting the harmful MBNL1-rCUG complex, demonstrating a strong inhibition constant (Ki) of 25±8 nm and correcting splicing defects in model cells.

While the compound is relatively nontoxic and improves disease symptoms in a Drosophila model, it has a low maximum tolerated dose in mice and limited cell uptake, indicating challenges for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Potent Inhibitor of Protein Sequestration by Expanded Triplet (CUG) Repeats that Shows Phenotypic Improvements in a Drosophila Model of Myotonic Dystrophy. Luu, LM., Nguyen, L., Peng, S., et al.[2018]

The small-molecule inhibitor tideglusib (TG) effectively normalizes the GSK3β-CUGBP1 pathway in myoblasts from patients with myotonic dystrophy type 1 (DM1), leading to reduced levels of harmful mutant DMPK mRNA.

In a mouse model of DM1, treatment with TG not only corrected the GSK3β pathway but also improved postnatal survival, growth, and neuromotor activity, suggesting a potential therapeutic approach for DM1 and congenital DM1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correction of Glycogen Synthase Kinase 3β in Myotonic Dystrophy 1 Reduces the Mutant RNA and Improves Postnatal Survival of DMSXL Mice. Wang, M., Weng, WC., Stock, L., et al.[2022]

Citations

1. Sweden pubmed.ncbi.nlm.nih.gov

Responsiveness of performance-based outcome measures for mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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

3. Netherlands pubmed.ncbi.nlm.nih.gov

Sleepiness and Sleep-related Breathing Disorders in Myotonic Dystrophy and Responses to Treatment: A Prospective Cohort Study. [2018]

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

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

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

Patient-reported impact of symptoms in myotonic dystrophy type 1 (PRISM-1). [2022]

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

High frequency of gastrointestinal manifestations in myotonic dystrophy type 1 and type 2. [2023]

7. Germany pubmed.ncbi.nlm.nih.gov

A Potent Inhibitor of Protein Sequestration by Expanded Triplet (CUG) Repeats that Shows Phenotypic Improvements in a Drosophila Model of Myotonic Dystrophy. [2018]

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

Correction of Glycogen Synthase Kinase 3β in Myotonic Dystrophy 1 Reduces the Mutant RNA and Improves Postnatal Survival of DMSXL Mice. [2022]