Dilated Cardiomyopathy (DCM)
Conditions
Keywords
Cardiomyopathy, Dilated, BAG3 Protein, human, dilated cardiomyopathy, DCM, BAG3, BCL2-associated Athanogene 3, Genetic Cardiomyopathy, Gene Therapy, Heart Failure, Ventricular Arrhythmia, Cardiovascular Diseases, Cardiomyopathies, Heart Diseases, Inherited heart disease, AAVrh.74
Brief 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.
Interventions
GENETICRP-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
Sponsors
Rocket Pharmaceuticals Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The single-group study will be composed of up to two sequential dose cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-emergent Adverse Events (TEAE) | Baseline up to End of Study (up to 24 months post-infusion) | Number of participants with Adverse Events following a single IV dose of RP-A701 |
| Incidence of Treatment-emergent Serious Adverse Events (SAE). | Baseline up to End of Study (up to 24 months post-infusion) | Number of participants with Serious Adverse Events (SAE) following a single IV dose of RP-A701 |
| Incidence of Dose Limiting Toxicities (DLT). | Baseline up to End of Study (up to 24 months post-infusion) | Number of participants with Dose Limiting Toxicities (DLT) following a single IV dose of RP-A701 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the impact of RP-A701 on features of cardiovascular function. | Baseline up to End of Study (up to 24 months post-infusion) | Change in measures of LV systolic function, including LV ejection fraction (LVEF), LV global longitudinal strain. |
| To assess the extent of RP-A701 transduction and protein expression. | Baseline up to End of Study (up to 24 months post-infusion) | Change in BAG3 myocardial protein expression |
| 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) | Change in symptoms of HF assessed by New York Heart Association (NYHA) class. |
| To assess the impact of RP-A701 on quality of life. | Baseline up to End of Study (up to 24 months post-infusion) | Change in Kansas City Cardiomyopathy Questionnaire (KCCQ-12) Overall Summary Score. |
Countries
United States
Contacts
CONTACTClinical Information
Outcome results
None listed