Testing RP-A601 for heart condition caused by PKP2 gene variants
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 study is testing a new treatment called RP-A601 to see if it can help adults with a heart condition caused by changes in the PKP2 gene.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 9 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Rocket Pharmaceuticals Inc. Industry-sponsored |
| Locations | 3 sites (La Jolla, California and 2 other locations) |
| Trial ID | NCT05885412 on ClinicalTrials.gov |
What this trial studies
This Phase 1 dose escalation trial evaluates the safety and preliminary efficacy of RP-A601, administered as a single intravenous infusion, in high-risk adult patients diagnosed with PKP2 variant-mediated arrhythmogenic cardiomyopathy (PKP2-ACM). The study aims to determine the appropriate dosing and monitor any adverse effects while assessing initial treatment responses. Participants must meet specific inclusion criteria, including a documented PKP2 variant and a history of implantable cardioverter-defibrillator (ICD) implantation.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with a confirmed diagnosis of PKP2-ACM and a history of ICD implantation.
Not a fit: Patients with cardiomyopathy due to genetic causes other than PKP2 truncating variants or those with severe right ventricular dysfunction may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with PKP2-ACM, potentially improving their heart function and reducing the risk of sudden cardiac death.
How similar studies have performed: While this approach is novel in the context of PKP2-ACM, similar gene-targeted therapies have shown promise in other genetic cardiomyopathies.
Eligibility criteria
Show full inclusion / exclusion 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.
Where this trial is running
La Jolla, California and 2 other locations
- University of California, San Diego — La Jolla, California, United States (Recruiting)
- Duke University — Durham, North Carolina, United States (Recruiting)
- Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (Withdrawn)
Study contacts
- Principal investigator: Barry Greenberg, MD — University of California, San Diego
- Study coordinator: Clinical Information
- Email: clinicaltrials@rocketpharma.com
- Phone: 646-627-0033
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.