A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy

A Phase 1 Dose Escalation Trial Evaluating an Intravenously Administered Recombinant Adeno-associated Virus Serotype rh.74 (AAVrh.74) Vector Containing the Human BCL2-associated Athanogene 3 (BAG3) Gene Coding Sequence (RP-A701) in Subjects With Dilated Cardiomyopathy Arising From Pathogenic BAG3 Variants (BAG3-DCM)

This is a Phase 1, open-label, dose-escalation trial to characterize the safety, tolerability, and preliminary efficacy of RP-A701 following a single IV administration in high-risk adult patients with BAG3-DCM.

Study Overview

• Status: Recruiting
• Conditions: Dilated Cardiomyopathy (DCM)
• Intervention / Treatment: Genetic: RP-A701 is a recombinant viral vector composed of an AAV serotype rh.74 (AAVrh.74) capsid encapsulating the transgene, BCL2-associated Athanogene 3 (BAG3)

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Information; Phone Number: 646-627-0033; Email: clinicaltrials@rocketpharma.com

Study Locations

• United States
  • California
    • San Diego, California, United States, 92037
      • Recruiting
      • University of California, San Diego
      • Principal Investigator: Barry Greenberg, MD
      • Contact: Clinical Research Coordinator; Phone Number: 858-822-1722; Email: emoyacespedes@health.ucsd.edu
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: John Giudicessi, MD, PhD
      • Contact: Clinical Research Coordinator; Phone Number: 507-538-1500; Email: slade.sierra@mayo.edu
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Daniel Judge, MD
      • Contact: Clinical Res; Phone Number: 843-792-2300; Email: andrewcl@musc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subjects are eligible for inclusion into the study only if all the following criteria apply:

1. Male or female between 18 and 65 years of age at the time of signing the informed consent
2. Capable of and willing to provide signed informed consent

3. Clinical diagnosis of DCM defined as and requiring each of the following:

   1. Mild to moderate systolic dysfunction (LVEF ≥ 25% and ≤ 45%) by echocardiography or CMR performed within 3 months of enrollment.
   2. Absence of severe coronary artery disease (>70% stenosis) or active myocardial ischemia as the etiology of LV systolic dysfunction
   3. Absence of uncontrolled hypertension, significant cardiac valve disease (i.e., greater than moderate in severity), infiltrative disorder, or systemic disease known to cause cardiomyopathy.
4. Documentation of a pathogenic or likely pathogenic variant in BAG3
5. History of ICD implantation ≥ 3 months prior to enrollment
6. NYHA Class II or III HF symptoms with stable HF therapeutic guideline-directed medical regimen for 30 days prior to enrollment

Exclusion Criteria:

1. CV disease that may be related to a genetic etiology other than a BAG3 pathogenic or likely pathogenic variant.
2. Previous participation in a study of gene transfer or gene editing.
3. I.V. inotropic, vasodilator, or diuretic therapy ≤ 30 days prior to enrollment.
4. History of intracardiac thrombosis or arterial thromboembolic events
5. Severe RV dysfunction assessed by echocardiogram or CMR ≤ 12 months prior to screening
6. LVEF < 25% by echocardiogram or CMR at ≤ 3 months prior to screening
7. NYHA Class I or IV HF

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single ascending dose of RP-A701 in up to 2 consecutive cohorts; Participants will receive a single intravenous dose of RP-A701 on Day 0 and will be followed for up to two years	Genetic: RP-A701 is a recombinant viral vector composed of an AAV serotype rh.74 (AAVrh.74) capsid encapsulating the transgene, BCL2-associated Athanogene 3 (BAG3); One-time treatment with a single ascending dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-emergent Adverse Events (TEAE)	Number of participants with Adverse Events following a single IV dose of RP-A701	Baseline up to End of Study (up to 24 months post-infusion)
Incidence of Treatment-emergent Serious Adverse Events (SAE).	Number of participants with Serious Adverse Events (SAE) following a single IV dose of RP-A701	Baseline up to End of Study (up to 24 months post-infusion)
Incidence of Dose Limiting Toxicities (DLT).	Number of participants with Dose Limiting Toxicities (DLT) following a single IV dose of RP-A701	Baseline up to End of Study (up to 24 months post-infusion)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of RP-A701 on features of cardiovascular function.	Change in measures of LV systolic function, including LV ejection fraction (LVEF), LV global longitudinal strain.	Baseline up to End of Study (up to 24 months post-infusion)
To assess the impact of RP-A701 on features of cardiovascular function.	Change in peak oxygen consumption (VO2) or ventilatory efficiency (VE/VCO2 slope) by cardiopulmonary exercise test (CPET)	Baseline up to End of Study (up to 24 months post-infusion)
To assess the impact of RP-A701 on features of cardiovascular function.	Change in 6-minute walk distance.	Baseline up to End of Study (up to 24 months post-infusion)
To assess the extent of RP-A701 transduction and protein expression.	Change in BAG3 myocardial protein expression	Baseline up to End of Study (up to 24 months post-infusion)
To assess the impact of RP-A701 on features of heart failure (HF).	Change in symptoms of HF assessed by New York Heart Association (NYHA) class.	Baseline up to End of Study (up to 24 months post-infusion)
To assess the impact of RP-A701 on quality of life.	Change in Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Overall Summary Score.	Baseline up to End of Study (up to 24 months post-infusion)

Collaborators and Investigators

• Sponsor: Rocket Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: July 25, 2025
• First Submitted That Met QC Criteria: August 20, 2025
• First Posted (Actual): August 22, 2025

Study Record Updates

• Last Update Posted (Actual): June 30, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiovascular Diseases; Gene Therapy; Cardiomyopathy; human; dilated cardiomyopathy; Heart Diseases; Ventricular Arrhythmia; Cardiomyopathies; DCM; Genetic Cardiomyopathy; Dilated; BAG3; BAG3 Protein; BCL2-associated Athanogene 3; Inherited heart disease; AAVrh.74
• Additional Relevant MeSH Terms: Laminopathies; Pathological Conditions, Anatomical; Genetic Diseases, Inborn; Cardiomegaly; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Heart Failure; Cardiovascular Diseases; Heart Diseases; Cardiomyopathies; Cardiomyopathy, Dilated; Dilatation, Pathologic
• Other Study ID Numbers: RP-A701-0125

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No