HELIOS-B: A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 655
- 试验地点
- 119
- 主要终点
- Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population
研究概览
简要总结
This study will evaluate the efficacy and safety of vutrisiran 25 mg administered subcutaneously (SC) once every 3 months (q3M) compared to placebo in participants with ATTR amyloidosis with cardiomyopathy.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a documented diagnosis of transthyretin (ATTR) amyloidosis with cardiomyopathy, classified as either hereditary ATTR (hATTR) amyloidosis with cardiomyopathy or wild-type ATTR (wtATTR) amyloidosis with cardiomyopathy meeting pre-specified diagnostic criteria
- •Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF OR clinical evidence of HF
排除标准
- •Has known primary amyloidosis or leptomeningeal amyloidosis
- •Has New York Heart Association (NYHA) Class IV heart failure
- •Has NYHA Class III heart failure AND is at high risk based on pre-specified criteria
- •Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV at the Screening visit
- •Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m^2
- •Has received prior TTR-lowering treatment
- •Has other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease
研究组 & 干预措施
Vutrisiran 25 mg
Participants received vutrisiran 25 milligrams (mg) administered subcutaneously (SC) once every 3 months (q3M) during the 36-month double-blind (DB) period. After the DB period, participants continue receiving vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the open-label treatment extension (OLE) period.
干预措施: Vutrisiran (Drug)
Placebo
Participants received vutrisiran matching placebo administered SC q3M during the 36-month DB period. After the DB period, participants receive vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the OLE period.
干预措施: Vutrisiran (Drug)
Placebo
Participants received vutrisiran matching placebo administered SC q3M during the 36-month DB period. After the DB period, participants receive vutrisiran, 25 mg, SC injection, q3M for up to 24 months in the OLE period.
干预措施: Sterile Normal Saline (0.9% NaCl) (Drug)
结局指标
主要结局
Composite Endpoint of All-Cause Mortality and Recurrent Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) in the Overall Population
时间窗: Up to Month 36
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
Composite Endpoint of All-Cause Mortality and Recurrent CV Events (CV Hospitalizations and Urgent HF Visits) in the Vutrisiran Monotherapy Subgroup
时间窗: Up to Month 36
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) were compared between treatment groups using a modified Andersen-Gill model with a robust variance. All-cause mortality included heart transplantation and LVAD placement events along with deaths; recurrent CV events included CV hospitalizations and urgent HF visits. The number of participants with at least one CV event or all-cause mortality event have been reported here. No imputation was done for participants who dropped out early for the primary analysis of this composite outcome endpoint.
次要结局
- Change From Baseline in 6-Minute Walk Test (6-MWT) in the Overall Population(Baseline to Month 30)
- Change From Baseline in 6-MWT in the Vutrisiran Monotherapy Subgroup(Baseline to Month 30)
- Change From Baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score in the Overall Population(Baseline to Month 30)
- Change From Baseline in the KCCQ-OS Score in the Vutrisiran Monotherapy Subgroup(Baseline to Month 30)
- All-cause Mortality in the Overall Population and Vutrisiran Monotherapy Subgroup(Up to 42 months)
- Percentage of Participants With Change in NYHA Class at Month 30 in the Overall Population(Baseline to Month 30)
- Percentage of Participants With Change in NYHA Class at Month 30 in the Vutrisiran Monotherapy Subgroup(Baseline to Month 30)