APOLLO-B: A Phase 3, Randomized, Double-blind, Placebo-controlled Multicenter Study to Evaluate the Efficacy and Safety of Patisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 360
- 试验地点
- 90
- 主要终点
- Change From Baseline at Month 12 in Six-Minute Walk Test (6-MWT)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of patisiran 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
- •Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hereditary ATTR amyloidosis with cardiomyopathy or wild-type ATTR amyloidosis with cardiomyopathy
- •Medical history of heart failure with at least 1 prior hospitalization for heart failure, or current clinical evidence (signs and symptoms of heart failure)
- •Clinically stable with no cardiovascular related hospitalizations within 6 weeks of study start
- •Has never taken tafamidis before (tafamidis naïve) or currently on tafamidis for ≥6 months with evidence of disease progression while on tafamidis treatment
- •Able to complete ≥150 m on the 6-minute walk test
- •Screening N-terminal pro B-type natriuretic peptide (NT-proBNP), a blood marker of heart failure severity, >300 ng/L and <8500 ng/L; in participants with permanent or persistent atrial fibrillation, screening NT-proBNP> 600 ng/L and <8500 ng/L
排除标准
- •Known primary amyloidosis (AL) or leptomeningeal amyloidosis.
- •Received prior TTR lowering treatment
- •New York Heart Association heart failure classification of III and at high risk
- •New York Heart Association heart failure classification of IV
- •Neuropathy requiring cane or stick to walk, or is wheelchair bound
- •Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m^2
- •Abnormal liver function
- •Has hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection
- •Has non-amyloid disease that significantly affects ability to walk (e.g., severe chronic obstructive pulmonary disease, severe arthritis, or peripheral vascular disease affecting ambulation)
- •Prior or planned heart, liver, or other organ transplant
- •Other cardiomyopathy not related to ATTR amyloidosis
研究组 & 干预措施
Patisiran
Participants will be administered multiple doses of patisiran in the double-blind and open-label extension period.
干预措施: Patisiran (Drug)
Placebo
Participants will be administered multiple doses of placebo in the double-blind period. In the open-label extension period, participants will be administered multiple doses of patisiran.
干预措施: Placebo (Drug)
Placebo
Participants will be administered multiple doses of placebo in the double-blind period. In the open-label extension period, participants will be administered multiple doses of patisiran.
干预措施: Patisiran (Drug)
结局指标
主要结局
Change From Baseline at Month 12 in Six-Minute Walk Test (6-MWT)
时间窗: Baseline, Month 12
Distance in meters walked in 6 minutes, longer distances indicate greater functional capacity. Missing 6MWT values due to non-COVID-19 death or inability to walk due to ATTR disease progression were imputed using the worst 10th percentile change observed in the DB period. Missing 6-MWT values due to other reasons are multiply imputed to create 100 complete datasets. The change from baseline is averaged across the 100 complete datasets.
次要结局
- Change From Baseline at Month 12 in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) Score(Baseline, Month 12)
- Composite Endpoint of All-Cause Mortality, Frequency of Cardiovascular (CV) Events (CV Hospitalizations and Urgent Heart Failure [HF] Visits) and Change From Baseline in 6-MWT Analyzed by Win Ratio(Up to Month 12)
- Composite Endpoint of All-cause Mortality and Frequency of All-cause Hospitalizations and Urgent HF Visits in All Participants(Up to Month 12)
- Composite Endpoint of All-Cause Mortality and Frequency of All-Cause Hospitalizations and Urgent HF Visits in Participants Not on Tafamidis at Baseline(Up to Month 12)