Targeted therapy for arrhythmogenic cardiomyopathy using tideglusib

Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy

This study is testing a new medication called tideglusib to see if it can help people with a specific genetic type of arrhythmogenic cardiomyopathy feel better and reduce their risk of serious heart problems.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hamilton Health Sciences Corporation (other)
• Locations: 17 sites (Calgary, Alberta and 16 other locations)
• Trial ID: NCT06174220 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy of tideglusib, a glycogen synthase kinase-3 β inhibitor, in patients with genotype positive arrhythmogenic cardiomyopathy (ACM). It is a multi-centre, prospective, randomized, double-blind, placebo-controlled trial designed to assess how this targeted therapy can address the underlying pathophysiology of ACM, which is characterized by myocardial fibrosis and a risk of sudden cardiac death. The study aims to recruit patients with specific genetic variants associated with ACM and monitor their response to treatment over time.

Who should consider this trial

Good fit: Ideal candidates for this study are individuals with a pathogenic or likely pathogenic desmosomal variant or the TMEM43-p.S358L variant, along with a clinical diagnosis of ACM.

Not a fit: Patients with NYHA class IV heart failure or those with ventricular scar secondary to coronary artery disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of sudden cardiac death in patients with arrhythmogenic cardiomyopathy.

How similar studies have performed: While there has been progress in understanding ACM, this specific approach using glycogen synthase kinase-3 inhibition is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

* A pathogenic or likely pathogenic desmosomal (PKP2, DSG2, DSC2, DSP, or JUP\*) rare variant OR the TMEM43-p.S358L variant

  \*JUP carriers must be homozygous or compound heterozygous
* Mean ≥ 500 PVCs per 24 hours on a baseline screening 7-day Holter monitor
* Clinical ACM diagnosis or recognition of genetic carrier status for ≥ 6 months prior to screening

Exclusion Criteria:

* NYHA class IV heart failure
* Ventricular scar secondary to coronary artery disease
* Initiation, cessation, or dose change of a Class I or III anti-arrhythmic drug in the 3 months prior to screening
* Any potentially harmful chronic liver disease
* ALT value \> 2X the upper limit of the normal reference range at Screening
* Total bilirubin value greater than the upper limit of the normal reference range at Screening, unless documented Gilbert's syndrome. For individuals with Gilbert's syndrome, total bilirubin value greater than 2-fold the upper limit of the normal reference range at Screening.
* A history of alcohol or illicit substance use disorders
* Regular and long-term use of strong CYP3A4 inhibitors, including clarithromycin, telithromycin, ketoconazole, itraconazole, posaconazole, nefazodone, idinavir and ritonavir
* Serum creatinine \> 150 micromole/L or creatinine clearance ≤ 60 mL/min (according to Cockcroft-Gault formula) at Screening
* Pregnant at time of enrollment and women of childbearing age who do not use a highly effective form of contraception
* Males, engaged in sexual relations with a female of child-bearing potential, not using an acceptable contraceptive method if not surgically sterile
* Patients unwilling to provide informed consent or comply with follow-up
* Hypersensitivity to tideglusib or any components of its formulation, including allergy to strawberry
* Concurrent use of drugs metabolized by CYP3A4 with a narrow therapeutic window e.g. warfarin and digoxin

Where this trial is running

Calgary, Alberta and 16 other locations

• University of Calgary — Calgary, Alberta, Canada (RECRUITING)
• University of British Columbia — Vancouver, British Columbia, Canada (RECRUITING)
• Victoria Cardiac Arrhythmia Trials Inc. — Victoria, British Columbia, Canada (RECRUITING)
• NL Health Services — St. John's, Newfoundland and Labrador, Canada (RECRUITING)
• Nova Scotia Health — Halifax, Nova Scotia, Canada (RECRUITING)
• Hamilton General Hospital — Hamilton, Ontario, Canada (RECRUITING)
• Kingston General Hospital — Kingston, Ontario, Canada (NOT_YET_RECRUITING)
• London Health Sciences Centre — London, Ontario, Canada (RECRUITING)
• Newmarket Electrophysiologist Research Group 'NERG' — Newmarket, Ontario, Canada (NOT_YET_RECRUITING)
• University of Ottawa Heart Institute — Ottawa, Ontario, Canada (NOT_YET_RECRUITING)
• Heart Health Institute Research Inc — Scarborough Village, Ontario, Canada (RECRUITING)
• Sunnybrook Health Sciences Centre — Toronto, Ontario, Canada (NOT_YET_RECRUITING)
• St. Michael's Hospital — Toronto, Ontario, Canada (NOT_YET_RECRUITING)
• Montreal Heart Institute — Montreal, Quebec, Canada (RECRUITING)
• McGill University Health Centre — Montreal, Quebec, Canada (NOT_YET_RECRUITING)
• Hopital du Sacré-Coeur de Montréal — Montreal, Quebec, Canada (NOT_YET_RECRUITING)
• University Institute of Cardiology and Pneumology of Quebec — Québec, Quebec, Canada (RECRUITING)

Study contacts

• Principal investigator: Jason D Roberts, MD MAS — McMaster University and Population Health Research Institute
• Study coordinator: Jason Roberts, MD MAS

Conditions: Arrhythmogenic Cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, sudden cardiac death, ventricular cardiomyopathy, genetics, arrhythmia