RP-A701 gene therapy for BAG3-related 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 Phase 1 study will try a one-time intravenous RP-A701 gene therapy in adults with BAG3-related dilated cardiomyopathy to see if it is safe and may improve heart function.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Rocket Pharmaceuticals Inc. (Industry-sponsored)
• Locations: 3 sites (San Diego, California and 2 other locations)
• Trial ID: NCT07137338 on ClinicalTrials.gov

What this trial studies

This open-label, dose-escalation Phase 1 trial gives a single IV dose of RP-A701, an AAVrh.74 vector carrying the BAG3 transgene, to adults with genetically confirmed BAG3-DCM. The primary goal is to characterize safety and tolerability across ascending dose cohorts, with preliminary efficacy measured by changes in LVEF, heart failure symptoms, and clinical events. Eligible participants have LVEF 25–45%, NYHA class II–III symptoms, a pathogenic or likely pathogenic BAG3 variant, and an implanted ICD for at least 3 months. Participants are enrolled at multiple U.S. centers and will undergo serial clinical, imaging, and laboratory monitoring over planned follow-up visits.

Who should consider this trial

Good fit: Ideal candidates are adults 18–65 with a pathogenic or likely pathogenic BAG3 variant, mild–moderate systolic dysfunction (LVEF 25–45%), NYHA class II–III symptoms, and an implanted ICD.

Not a fit: Patients without a confirmed BAG3 pathogenic variant, with alternate causes of cardiomyopathy (for example severe coronary artery disease), uncontrolled hypertension, significant valvular disease, very low LVEF (<25%), or outside the age range are unlikely to benefit from this therapy.

Why it matters

Potential benefit: If successful, RP-A701 could restore BAG3 function in heart muscle, potentially improving cardiac function and slowing progression of heart failure in people with BAG3-DCM.

How similar studies have performed: AAV-based gene therapies have shown promise in other genetic cardiac and neuromuscular conditions, but BAG3-targeted therapy is novel and currently has limited clinical evidence.

Eligibility criteria

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

Where this trial is running

San Diego, California and 2 other locations

• University of California, San Diego — San Diego, California, United States (Recruiting)
• Mayo Clinic — Rochester, Minnesota, United States (Recruiting)
• Medical University of South Carolina — Charleston, South Carolina, United States (Recruiting)

Study contacts

• Study coordinator: Clinical Information

Conditions Dilated Cardiomyopathy; Cardiomyopathy; Dilated; BAG3 Protein; human; dilated cardiomyopathy; DCM; BAG3