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

PHRI.TaRGET

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.

2024-04-01

2026-02-01

2026-07-01

Not yet recruiting

Early phase I

120

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Patients will be randomized in a 1:1 ratio using an automated central, web-based system within 30 days of completing their baseline Holter. Randomization will be stratified by TMEM43-p.S358L variant status.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}}, 'enrollmentInfo': {'count': 120, 'type': 'ESTIMATED'}}

2024-02-22