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

• Status: Not yet recruiting
• Trial end date: 2026-07-01
• Target enrollment: 0
• Participant gender: All

Summary

The TaRGET study is a multi-centre, prospective, randomized, double-blind, placebo-controlled trial designed to evaluate the potential therapeutic efficacy of tideglusib, a glycogen synthase kinase-3 β inhibitor, in genotype positive arrhythmogenic cardiomyopathy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hamilton Health Sciences Corporation
• Collaborators: AMO Pharma; Canadian Institutes of Health Research (CIHR); Canadian SADS; Hearts in Rhythm Organization (HiRO); Population Health Research Institute

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