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)

Plain English Summary

A Phase 1 AAV Gene Therapy Trial Evaluating Safety and Preliminary Efficacy of RP-A701 in Subjects With BAG3 Dilated Cardiomyopathy is a Phase 1 clinical trial sponsored by Rocket Pharmaceuticals Inc. studying Dilated Cardiomyopathy (DCM). This trial tests a new gene therapy called RP-A701 for a specific type of heart muscle disease. It is for adults with dilated cardiomyopathy caused by a genetic change in the BAG3 gene. Participants will receive a single dose of the gene therapy intravenously. Currently, treatment options focus on managing symptoms; this therapy aims to address the underlying genetic cause. The trial aims to enroll 8 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18-65 with a confirmed genetic cause (BAG3 variant) for their dilated cardiomyopathy. Patients must have mild to moderate heart muscle weakness (ejection fraction between 25% and 45%) and stable heart failure symptoms. Individuals with other significant heart conditions, recent heart attacks, uncontrolled high blood pressure, or previous gene therapy are excluded. This trial is studying Dilated Cardiomyopathy (DCM), so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure the safety of the gene therapy by tracking any side effects, serious adverse events, and dose-limiting toxicities, ensuring patient well-being during treatment. The specific primary outcome measures are: Incidence of Treatment-emergent Adverse Events (TEAE) (Baseline up to End of Study (up to 24 months post-infusion)); Incidence of Treatment-emergent Serious Adverse Events (SAE). (Baseline up to End of Study (up to 24 months post-infusion)); Incidence of Dose Limiting Toxicities (DLT). (Baseline up to End of Study (up to 24 months post-infusion)). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a critical unmet need for a genetic heart condition where current treatments only manage symptoms, offering a potential one-time cure by correcting the underlying genetic defect. This research targets Dilated Cardiomyopathy (DCM), where improved treatment options are needed.

Investor Insight

This trial represents an early-stage investment in a novel gene therapy for a rare genetic disorder, with potential for significant impact if successful, though approval probability is low at this ear Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific risks and benefits of gene therapy for your condition. Participation involves a single intravenous infusion of the gene therapy, followed by regular monitoring for up to two years. You will need to have a history of an implanted defibrillator and be on stable heart failure medication. This trial is currently recruiting participants. The trial is being conducted at 3 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 8 participants

Interventions

• 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

Primary Outcomes

• Incidence of Treatment-emergent Adverse Events (TEAE) (Baseline up to End of Study (up to 24 months post-infusion))
• Incidence of Treatment-emergent Serious Adverse Events (SAE). (Baseline up to End of Study (up to 24 months post-infusion))
• Incidence of Dose Limiting Toxicities (DLT). (Baseline up to End of Study (up to 24 months post-infusion))

Secondary Outcomes

• To assess the impact of RP-A701 on features of cardiovascular function. (Baseline up to End of Study (up to 24 months post-infusion))
• To assess the impact of RP-A701 on features of cardiovascular function. (Baseline up to End of Study (up to 24 months post-infusion))
• To assess the impact of RP-A701 on features of cardiovascular function. (Baseline up to End of Study (up to 24 months post-infusion))
• To assess the extent of RP-A701 transduction and 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). (Baseline up to End of Study (up to 24 months post-infusion))

Full 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

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Dilated Cardiomyopathy
• Heart Failure
• Genetic Disorders
• Cardiomyopathy
• Arrhythmia
• Sudden Cardiac Death
• Congestive Heart Failure
• Myocardial Dysfunction
• Inherited Cardiac Diseases
• Gene Therapy

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