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

April 14, 2026 updated by: Rocket Pharmaceuticals Inc.

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • La Jolla, California, United States, 92037
        • Recruiting
        • University of California, San Diego
        • Contact:
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Recruiting
        • Duke University
        • Contact:
        • Principal Investigator:
          • James Daubert, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Withdrawn
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: RP-A601
Single ascending dose of RP-A601 in 2 consecutive cohorts
Genetic: RP-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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rocket Pharmaceuticals Inc.

Investigators

  • Principal Investigator: Barry Greenberg, MD, University of California, San Diego

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 29, 2023

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

September 1, 2029

Study Registration Dates

First Submitted

May 22, 2023

First Submitted That Met QC Criteria

May 22, 2023

First Posted (Actual)

June 2, 2023

Study Record Updates

Last Update Posted (Actual)

April 16, 2026

Last Update Submitted That Met QC Criteria

April 14, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RP-A601-0323

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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