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

Phase 1

Recruiting

• Conditions: PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM)
• Interventions: Genetic: RP-A601

• Registration Number: NCT05885412
• Lead Sponsor: Rocket Pharmaceuticals Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-22
• Study First Submitted QC: 2023-05-22
• Study First Posted: 2023-06-02
• Study Start: 2023-08-29
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-02
• Last Update Posted: 2024-10-04
• Primary Completion: 2025-09
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 9

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
RP-A601	RP-A601	Single ascending dose of RP-A601 in 2 consecutive cohorts

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (3)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

University of California, San Diego; 🇺🇸 La Jolla, California, United States