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

Официальное название

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)

Обзор

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.

Вмешательства

• Генная терапия 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

Первичные конечные точки

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

Вторичные конечные точки (6)

• To assess the impact of RP-A701 on features of cardiovascular function. [Срок оценки: Baseline up to End of Study (up to 24 months post-infusion)]
• To assess the impact of RP-A701 on features of cardiovascular function. [Срок оценки: Baseline up to End of Study (up to 24 months post-infusion)]
• To assess the impact of RP-A701 on features of cardiovascular function. [Срок оценки: Baseline up to End of Study (up to 24 months post-infusion)]
• To assess the extent of RP-A701 transduction and protein expression. [Срок оценки: 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). [Срок оценки: Baseline up to End of Study (up to 24 months post-infusion)]
• To assess the impact of RP-A701 on quality of life. [Срок оценки: Baseline up to End of Study (up to 24 months post-infusion)]

Критерии участия

Критерии включения

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

• Male or female between 18 and 65 years of age at the time of signing the informed consent
• Capable of and willing to provide signed informed consent
• Clinical diagnosis of DCM defined as and requiring each of the following:

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

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• University of California, San Diego — San Diego
• Mayo Clinic — Rochester
• Medical University of South Carolina — Charleston

Идентификаторы

NCT: NCT07137338 · RP-A701-0125

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗