A Phase 1b, Pilot Trial Evaluating the Safety and Pharmacodynamic Effects of SRD-001 (AAV1-SERCA2a) in Subjects With Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 10
- 试验地点
- 4
- 主要终点
- Change in pulmonary capillary wedge pressure (PCWP)
研究概览
简要总结
The goal of this clinical trial is to test an experimental gene therapy in participants with heart failure with preserved ejection fraction, also known as diastolic heart failure. The main questions it aims to answer are:
- safety and tolerability of the gene therapy; and
- whether the gene therapy helps the heart ventricles relax during filling. Participants will undergo a one-time infusion of the gene therapy in the cardiac catheterization laboratory and then be followed for safety and effects on left-sided filling pressures while exercising. The first year will have multiple in-person visits followed by 4 years of biannual phone calls.
详细描述
Eligible participants will undergo a one-time antegrade epicardial coronary artery infusion of gene therapy delivered to the 3 major cardiac territories of the left ventricle of the heart (anterior, lateral, inferior/posterior) or bypass grafts unless contraindicated. Post-procedure, the subject will be monitored continuously for a minimum of 4 hours and then discharged to home that same day if medically appropriate. Participants will be followed for 52 weeks as part of the main trial. On Day 2 and Week 1, subjects will be contacted by phone for a general safety assessment, and if clinically indicated, an in-person evaluation and assessment will be performed as soon as possible. On Weeks 2, 4, 12, 24 and 52, subjects will undergo general safety assessments. Additionally, at Weeks 24 and 52, subjects will undergo outpatient core resting and exercise transthoracic echocardiography, right heart catheterization with hemodynamic monitoring and gas exchange measurements, 6-minute wall test, cardiac biomarker testing and completion the Kansas City Cardiomyopathy Questionnaire. Upon completion of the active observation period, participants will continue to be followed for 4 years with bi-annual, semi-structured telephone or in-person questionnaires that collect information on overall status and other comorbid conditions of interest in gene therapy trials.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide informed consent
- •Negative for anti-AAV1 neutralizing antibodies
- •NYHA class II or III
- •Left ventricular ejection fraction ≥ 50%
- •Evidence of resting or exercise-induced left ventricle filling pressure
- •On oral diuretic therapy
- •Adequate birth control
排除标准
- •NYHA class IV
- •Heart failure requiring hospitalization in the past 3 months
- •Manifested or provocable ischemic heart disease
- •Atrial fibrillation
- •History of congenital heart disease, restrictive or infiltrative cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm
- •History of amyloidosis
- •Untreated left-sided valvular disease
- •Severe COPD
- •BMI > 50 kg/m^2
- •Severe liver, kidney or hematologic dysfunction
- •Cancer within the past 5 years
- •Unstable concurrent conditions
结局指标
主要结局
Change in pulmonary capillary wedge pressure (PCWP)
时间窗: Week 24 and Week 52
PCWP assessed by right heart catheterization; change in mmHg from baseline
次要结局
- Change in oxygen uptake (VO2) during exercise(Week 24 and Week 52)
- Change in NT-proBNP(Week 24 and Week 52)
- Change in 6 Minute Walk Test Borg scale(Week 24 and Week 52)
- Change in New York Heart Association class(Week 24 and Week 52)
- Change in PCWP at 20W exercise(Week 24 and Week 52)
- Change in left atrial contractile strain(Week 24 and Week 52)
- Change in left ventricular (LV) relaxation(Week 24 and Week 52)
- Change in left atrial end systolic volume(Week 24 and Week 52)
- Change in left atrial reservoir strain(Week 24 and Week 52)
- Change in 6 Minute Walk Distance(Week 24 and Week 52)
- Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score(Week 24 and Week 52)