PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM)Phase 1NCT05885412
A Phase 1, Dose Escalation Trial of RP-A601 in Subjects With PKP2 Variant-Mediated Arrhythmogenic Cardiomyopathy (PKP2-ACM)
A Phase 1 study testing RP-A601 in people with PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM), run by Rocket Pharmaceuticals Inc. at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM)
- What is being tested?
- RP-A601
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 3 sitesUnited States
- Study dates
- 29 Aug 2023to Sep 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female ≥18 years at the time of signing the informed consent
- Capable and willing to provide signed informed consent
- Clinical diagnosis of ACM as defined by the 2010 revised Task Force Criteria (TFC)
- Documentation of a pathogenic or likely pathogenic truncating variant in PKP2
- History of Implantable Cardioverter-Defibrillator (ICD) implantation ≥6 months prior to enrollment
- PVC frequency ≥500 per 24 hours by ambulatory rhythm monitoring
- Left ventricular ejection fraction by echocardiogram or CMR ≥50%
Who cannot join
- Anti-AAVrh.74 capsid neutralizing antibody titer of >1:40
- Cardiomyopathy related to a genetic etiology other than PKP2 truncating variant
- Previous participation in a study of gene transfer or gene editing
- Severe Right Ventricular (RV) dysfunction
- New York Heart Association (NYHA) Class IV heart failure.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States3 sites, 2 recruiting
- Recruiting
Duke University
Durham, North Carolina, 27710
Meghan Pergola, MPH, meghan.pergola@duke.edu
James Daubert, MD
- Recruiting
University of California, San Diego
La Jolla, California, 92037
Barry Greenberg, MD, 858-246-2987, Bgreenberg@health.ucsd.edu
- Withdrawn
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
- Being tested
- RP-A601
- 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
- Medical subject headings
- Arrhythmogenic Right Ventricular Dysplasia, Death, Sudden, Cardiac, Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RP-A601Genetic
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 group | Role | What they receive |
|---|---|---|
| RP-A601 | Experimental | Single ascending dose of RP-A601 in 2 consecutive cohorts Receives: Genetic: RP-A601 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of safety associated with RP-A601
Incidence of treatment emergent adverse events (TEAEs), incidence of Serious Adverse Events (SAEs), and identification of Dose Limiting Toxicities (DLTs)
Measured: 12 months post-infusion
Secondary outcomes (3)
Preliminary efficacy of RP-A601 - Myocardial PKP2 protein expression
Assessment of changes in myocardial PKP2 protein expression
Measured: 12 months post-infusion
Preliminary efficacy of RP-A601 - Ventricular ectopy and arrhythmia
Assessment of changes in levels of ventricular ectopy and arrhythmia on cardiac rhythm monitoring
Measured: 12 months post-infusion
Preliminary efficacy of RP-A601 - Cardiac biomarkers
Assessment of changes in circulating levels of cardiac biomarkers of injury and stress
Measured: 12 months post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2023
- Study start29 Aug 2023
- Primary completionSep 2028 (estimated)
- Study completionSep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM)Studies of the same condition, open and under way.
- More trials run by Rocket Pharmaceuticals Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rocket Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Barry Greenberg, MD, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05885412
- Sponsor's protocol ID
- RP-A601-0323
- Status last verified
- Apr 2026
- First submitted
- 22 May 2023
- Last updated
- 16 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Alexandrino FB, Faaborg-Andersen CC, daSilva-deAbreu A. Anticoagulation in patients with atrial fibrillation and heart failure: More than meets the eye? Int J Cardiol. 2024 Feb 15;397:131591. doi: 10.1016/j.ijcard.2023.131591. Epub 2023 Nov 17. No abstract available.
PubMed 37979797
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05885412
- Acronym / sponsor ID
- RP-A601-0323
- Keywords
- Arrhythmogenic cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, Arrhythmogenic Right Ventricular Dysplasia, Sudden Cardiac Death, Genetic cardiomyopathy, Gene therapy, PKP2, ARVC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Rocket Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 29 Aug 2023 (actual)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2029 (estimated)
- First posted
- 2 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RP-A601 | Experimental | Genetic: RP-A601Single ascending dose of RP-A601 in 2 consecutive cohorts |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female ≥18 years at the time of signing the informed consent
- Capable and willing to provide signed informed consent
- Clinical diagnosis of ACM as defined by the 2010 revised Task Force Criteria (TFC)
- Documentation of a pathogenic or likely pathogenic truncating variant in PKP2
- History of Implantable Cardioverter-Defibrillator (ICD) implantation ≥6 months prior to enrollment
Key exclusion criteria (5 listed)
- Anti-AAVrh.74 capsid neutralizing antibody titer of >1:40
- Cardiomyopathy related to a genetic etiology other than PKP2 truncating variant
- Previous participation in a study of gene transfer or gene editing
- Severe Right Ventricular (RV) dysfunction
- New York Heart Association (NYHA) Class IV heart failure.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RP-A601RP-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) | Genetic | RP-A601 |
Primary outcome
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)
3 secondary outcomes
Preliminary efficacy of RP-A601 - Myocardial PKP2 protein expression
Time frame: 12 months post-infusion
Preliminary efficacy of RP-A601 - Ventricular ectopy and arrhythmia
Time frame: 12 months post-infusion
Preliminary efficacy of RP-A601 - Cardiac biomarkers
Time frame: 12 months post-infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Derived from this study: PubMed 37979797Alexandrino FB, Faaborg-Andersen CC, daSilva-deAbreu A. Anticoagulation in patients with atrial fibrillation and heart failure: More than meets the eye? Int J Cardiol. 2024 Feb 15;397:131591. doi: 10.1016/j.ijcard.2023.131591. Epub 2023 Nov 17. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Barry Greenberg, MD principal investigator
University of California, San Diego
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RP-A601 in people with PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM), run by Rocket Pharmaceuticals Inc. at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clinical Information (646-627-0033, clinicaltrials@rocketpharma.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluation of safety associated with RP-A601 (time frame: 12 months post-infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05885412, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.