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

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, eng…