A Phase 1/2 Trial of the Safety and Efficacy of SRD-001 (AAV1/SERCA2a) in Subjects With Heart Failure With Reduced Ejection Fraction
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 57
- 试验地点
- 5
- 主要终点
- Change from baseline in symptomatic parameters
研究概览
简要总结
It is believed that targeted SERCA2a enzyme replacement in HFrEF patients will correct defective intracellular Ca2+ hemostasis, resulting in improved cardiac contractile function and energetics which will, in turn, translate to improved clinical outcomes. Additionally, it is hypothesized that correcting SERCA2a dysfunction will also improve coronary blood flow through correction of the impaired endothelium-dependent nitric oxide-mediated vasodilatation observed in heart failure.
详细描述
MUSIC-HFrEF1 is an interventional study of SRD-001, an adeno-associated virus serotype 1 (AAV1) vector expressing the transgene for sarco(endo)plasmic reticulum Ca2+ ATPase 2a isoform (SERCA2a), in anti-AAV1 neutralizing antibody (NAb) negative subjects with ischemic or non-ischemic cardiomyopathy and New York Heart Association (NYHA) class III/IV symptoms of heart failure with reduced ejection fraction (HFrEF).
The Phase 1 trial is an open-label, uncontrolled study investigating two doses of SRD-001 at 3E13 and 4.5E13 viral genomes (vg) in 3-4 participants at each dose level.
The Phase 2 trial is a randomized, double-blind, placebo-controlled trial with prospective assignment to a single dose of either SRD-001 or placebo in a 1:1 ratio and a total sample size of N=50.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic ischemic or non-ischemic cardiomyopathy
- •NYHA class III/IV
- •LVEF ≤35%
- •Guideline-directed medical therapy for heart failure; ICD
排除标准
- •Restrictive cardiomyopathy, hypertrophic cardiomyopathy, acute myocarditis, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease or discrete left ventricular (LV) aneurysm
- •Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), mechanical circulatory support device (MCSD) or cardiac shunt
- •Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, conventional revascularization procedure or valvular repair in the 6 months following treatment
- •Likely need for an immediate heart transplant or MCSD implant due to hemodynamic instability
- •Inadequate hepatic and renal function
- •Diagnosis of, or treatment for, any cancer within the last 5 years except for basal cell carcinoma or carcinomas in situ where surgical excision was considered curative
研究组 & 干预措施
SRD-001
3E13 or 4.5E13 vg; one-time intracoronary infusion
干预措施: SRD-001 (Biological)
Placebo
One-time intracoronary infusion
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in symptomatic parameters
时间窗: Baseline to Month 6 and Month 12
Quality of life as assessed by Kansas City Cardiomyopathy Questionnaire: 0-24, very poor to poor; 25-49, poor to fair; 50-74, fair to good; and 75-100, good to excellent
Change from baseline in physical parameter
时间窗: Baseline to Month 6 and Month 12
Distance walked during the 6MWT
Change from baseline in LV function/remodeling
时间窗: Baseline to Month 6 and Month 12
Left ventricular end systolic volume (LVESV) as assessed by echocardiography
Rate of adverse events
时间窗: 6 and 12 months
Treatment-emergent adverse events
Rate of recurrent events
时间窗: Baseline to Month 6 and Month 12
HF-related hospitalization, ambulatory worsening heart failure, all-cause death, MCSD and transplant
次要结局
- Incidence of abnormal laboratory test results(Baseline to Month 6 and Month 12)
- Incidence of abnormal ECG results(Baseline to Month 6 and Month 12)
- Proportion of subjects who complete the trial(12 months)
- Concomitant medication use(6 and 12 months)
- Incidence of abnormal findings from interrogation of implantable cardioverter defibrillator(Baseline to Month 6 and Month 12)
- Incidence of abnormal physical examination findings(Baseline to Month 6 and Month 12)