Back to resultsA Phase 1, Dose Escalation Trial of RP-A601 in Subjects With PKP2 Variant-Mediated Arrhythmogenic Cardiomyopathy (PKP2-ACM)
Primary Purpose
PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM)
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RP-A601
Sponsored by
About this trial
This is an interventional treatment trial for PKP2 Arrhythmogenic Cardiomyopathy (PKP2-ACM) focused on measuring Arrhythmogenic cardiomyopathy, Arrhythmogenic Right Ventricular Cardiomyopathy, Arrhythmogenic Right Ventricular Dysplasia, Sudden Cardiac Death, Genetic cardiomyopathy, Gene therapy, PKP2, ARVC, ARVD, ACM, Cardiac Arrest, Ventricular Arrythmia
Eligibility Criteria
Key Inclusion Criteria: 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 Anti-AAVrh.74 capsid neutralizing antibody assay ≤1:40 History of Implantable Cardioverter-Defibrillator (ICD) implantation ≥6 months prior to enrollment Key Exclusion Criteria: 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 Left ventricular ejection fraction by echocardiogram ≤50% New York Heart Association (NYHA) Class IV heart failure.
Sites / Locations
- University of California, San DiegoRecruiting
- Children's Hospital of Philadelphia
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
RP-A601
Arm Description
Single ascending dose of RP-A601 in 2 consecutive cohorts
Outcomes
Primary Outcome Measures
Incidence of treatment emergent adverse events (TEAEs)
Evaluation of safety associated with RP-A601
Incidence of Serious Adverse Events (SAEs)
Evaluation of safety associated with RP-A601
Identification of Dose Limiting Toxicities (DLTs)
Evaluation of safety associated with RP-A601
Secondary Outcome Measures
Change in PKP2 myocardial tissue expression
Preliminary Efficacy: Extent of RP-A601 transduction through assessment of protein expression
Change in the frequency of clinical markers of life threatening arrhythmias
Preliminary Efficacy: Clinical impact of RP-A601
Full Information
NCT ID
NCT05885412
First Posted
May 22, 2023
Last Updated
October 9, 2023
Sponsor
Rocket Pharmaceuticals Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05885412
Brief Title
A Phase 1, Dose Escalation Trial of RP-A601 in Subjects With PKP2 Variant-Mediated Arrhythmogenic Cardiomyopathy (PKP2-ACM)
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)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 29, 2023 (Actual)
Primary Completion Date
September 2025 (Anticipated)
Study Completion Date
September 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rocket Pharmaceuticals Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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 Arrythmia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RP-A601
Arm Type
Experimental
Arm Description
Single ascending dose of RP-A601 in 2 consecutive cohorts
Intervention Type
Genetic
Intervention Name(s)
RP-A601
Intervention Description
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)
Primary Outcome Measure Information:
Title
Incidence of treatment emergent adverse events (TEAEs)
Description
Evaluation of safety associated with RP-A601
Time Frame
12 months post-infusion
Title
Incidence of Serious Adverse Events (SAEs)
Description
Evaluation of safety associated with RP-A601
Time Frame
12 months post-infusion
Title
Identification of Dose Limiting Toxicities (DLTs)
Description
Evaluation of safety associated with RP-A601
Time Frame
12 months post-infusion
Secondary Outcome Measure Information:
Title
Change in PKP2 myocardial tissue expression
Description
Preliminary Efficacy: Extent of RP-A601 transduction through assessment of protein expression
Time Frame
12 months post-infusion
Title
Change in the frequency of clinical markers of life threatening arrhythmias
Description
Preliminary Efficacy: Clinical impact of RP-A601
Time Frame
12 months post-infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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
Anti-AAVrh.74 capsid neutralizing antibody assay ≤1:40
History of Implantable Cardioverter-Defibrillator (ICD) implantation ≥6 months prior to enrollment
Key Exclusion Criteria:
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
Left ventricular ejection fraction by echocardiogram ≤50%
New York Heart Association (NYHA) Class IV heart failure.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Clinical Information
Phone
646-627-0033
Email
clinicaltrials@rocketpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barry Greenberg, MD
Organizational Affiliation
University of California, San Diego
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of California, San Diego
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Barry Greenberg, MD
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Rossano, MD
12. IPD Sharing Statement
Learn more about this trial
A Phase 1, Dose Escalation Trial of RP-A601 in Subjects With PKP2 Variant-Mediated Arrhythmogenic Cardiomyopathy (PKP2-ACM)
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