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

A Phase 1 Dose Escalation Trial Evaluating an Intravenously Administered Recombinant Adeno-Associated Virus Serotype rh.74 (AAVrh.74) Vector Containing the Human Plakophilin-2a (PKP2a) Coding Sequence (RP-A601; AAVrh.74-PKP2a) in Subjects With Arrhythmogenic Cardiomyopathy Arising From Pathogenic PKP2 Variants (PKP2-ACM)

Status

Recruiting

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05885412

Enrollment

Registered

2023-06-02

Start date

2023-08-29

Completion date

2029-09-01

Last updated

2026-04-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM)

Keywords

Arrhythmogenic cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, Arrhythmogenic Right Ventricular Dysplasia, Sudden Cardiac Death, Genetic cardiomyopathy, Gene therapy, PKP2, ARVC, ARVD, ACM, Cardiac Arrest, Ventricular Arrhythmia

Brief summary

This Phase 1 dose escalation trial will assess the safety and preliminary efficacy of a single dose intravenous infusion of RP-A601 in high-risk adult patients with PKP2-ACM.

Interventions

GENETICRP-A601

RP-A601 is a recombinant viral vector composed of an AAV serotype rh.74 (AAVrh.74) capsid encapsulating the transgene, human plakophilin 2 (PKP2), transcript variant 2a (PKP2a)

Study design

Allocation

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Key Inclusion Criteria: 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% Key

Exclusion criteria

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.

Design outcomes

Primary

Measure	Time frame	Description
Evaluation of safety associated with RP-A601	12 months post-infusion	Incidence of treatment emergent adverse events (TEAEs), incidence of Serious Adverse Events (SAEs), and identification of Dose Limiting Toxicities (DLTs)

Secondary

Measure	Time frame	Description
Preliminary efficacy of RP-A601 - Myocardial PKP2 protein expression	12 months post-infusion	Assessment of changes in myocardial PKP2 protein expression
Preliminary efficacy of RP-A601 - Ventricular ectopy and arrhythmia	12 months post-infusion	Assessment of changes in levels of ventricular ectopy and arrhythmia on cardiac rhythm monitoring
Preliminary efficacy of RP-A601 - Cardiac biomarkers	12 months post-infusion	Assessment of changes in circulating levels of cardiac biomarkers of injury and stress

Countries

United States

Contacts

CONTACTClinical Information

clinicaltrials@rocketpharma.com646-627-0033

PRINCIPAL_INVESTIGATORBarry Greenberg, MD

University of California, San Diego

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Apr 17, 2026