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)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 8
- 试验地点
- 3
- 主要终点
- Incidence of Treatment-emergent Adverse Events (TEAE)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Single ascending dose of RP-A701 in up to 2 consecutive cohorts
Participants will receive a single intravenous dose of RP-A701 on Day 0 and will be followed for up to two years
干预措施: 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) (Genetic)
结局指标
主要结局
Incidence of Treatment-emergent Adverse Events (TEAE)
时间窗: 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).
时间窗: 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).
时间窗: 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
次要结局
- 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 quality of life.(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))
- To assess the impact of RP-A701 on features of cardiovascular function.(Baseline up to End of Study (up to 24 months post-infusion))