A Phase 1, Dose Escalation Trial of RP-A601 in Subjects With PKP2 Variant-Mediated Arrhythmogenic Cardiomyopathy (PKP2-ACM)

Open to people ages 18 years and up

1. Male or female ≥18 years at the time of signing the informed consent
2. Capable and willing to provide signed informed consent
3. Clinical diagnosis of ACM as defined by the 2010 revised Task Force Criteria (TFC)
4. Documentation of a pathogenic or likely pathogenic truncating variant in PKP2
5. History of Implantable Cardioverter-Defibrillator (ICD) implantation ≥6 months prior to enrollment
6. PVC frequency ≥500 per 24 hours by ambulatory rhythm monitoring
7. Left ventricular ejection fraction by echocardiogram or CMR ≥50%

1. Anti-AAVrh.74 capsid neutralizing antibody titer of >1:40
2. Cardiomyopathy related to a genetic etiology other than PKP2 truncating variant
3. Previous participation in a study of gene transfer or gene editing
4. Severe Right ventricular (RV) dysfunction
5. New York Heart Association (NYHA) Class IV heart failure.