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

Rocket Pharmaceuticals

Status and phase: Begins enrollment in 3 months; Phase 1

Conditions: Dilated Cardiomyopathy (DCM)

Treatments: 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

Funder types: Industry

Identifiers

NCT07137338

RP-A701-0125

Details and patient eligibility

About

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.

Enrollment: 8 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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8 participants in 1 patient group

Single ascending dose of RP-A701 in up to 2 consecutive cohorts

Experimental group

Description:

Participants will receive a single intravenous dose of RP-A701 on Day 0 and will be followed for up to two years

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)