TRITON-CM: A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Nucresiran in Patients With Transthyretin-Mediated Amyloidosis With Cardiomyopathy (ATTR Amyloidosis With Cardiomyopathy)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,750
- 试验地点
- 266
- 主要终点
- Composite outcome of all-cause mortality and recurrent cardiovascular [CV] events (CV hospitalizations and urgent heart failure [HF] visits)
研究概览
简要总结
The purpose of this study is to:
- Evaluate the efficacy of nucresiran compared to placebo on reducing all-cause mortality and cardiovascular (CV) events
- Evaluate the efficacy of nucresiran compared to placebo on additional assessments of CV events and/or death
- Evaluate the efficacy of nucresiran compared to placebo on patient-reported health status and health-related quality of life
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 documented diagnosis of ATTR amyloidosis with cardiomyopathy including those with hereditary ATTR (hATTR) or wild-type ATTR (wATTR) amyloidosis.
- •Has medical history of heart failure (HF) with at least 1 prior hospitalization for HF or signs and symptoms that require treatment with a diuretic.
- •Has screening N-terminal prohormone B-type natriuretic peptide (NT-proBNP) >300 ng/L and <8500 ng/L; In patients with permanent or persistent atrial fibrillation, screening NT-proBNP >600 ng/L and <8500 ng/L.
- •Patients may be receiving approved TTR stabilizers for ATTR amyloidosis (eg, tafamidis, acoramidis) and may be receiving background therapy for HF at the discretion of the Investigator.
排除标准
- •Has New York Heart Association (NYHA) Class IV HF; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage
- •Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV.
- •Has an estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73m^2 at screening.
- •Has received prior or currently receiving TTR-lowering therapy
研究组 & 干预措施
Placebo
Participants will receive placebo administered subcutaneously (SC) once every 6 months (q6M) during the double-blind (DB) period, followed by nucresiran 300 mg administered SC q6M during the open-label extension (OLE) period.
干预措施: Sterile Normal Saline (0.9% NaCl) (Drug)
Nucresiran 300 mg
Participants will receive nucresiran 300 mg administered SC Q6M during the DB period, followed by nucresiran 300 mg administered SC q6M during the OLE period.
干预措施: Nucresiran (Drug)
Placebo
Participants will receive placebo administered subcutaneously (SC) once every 6 months (q6M) during the double-blind (DB) period, followed by nucresiran 300 mg administered SC q6M during the open-label extension (OLE) period.
干预措施: Nucresiran (Drug)
结局指标
主要结局
Composite outcome of all-cause mortality and recurrent cardiovascular [CV] events (CV hospitalizations and urgent heart failure [HF] visits)
时间窗: Baseline to end of double-blind period (estimated 32 months, maximum 5 years)
All-cause mortality and recurrent CV events (CV hospitalizations and urgent HF visits) will be compared between treatment groups using an Andersen-Gill model.
次要结局
- All-cause mortality(Baseline to end of double-blind period (estimated 32 months, maximum 5 years))
- Time to first CV event (CV hospitalizations and urgent HF visits) or all-cause mortality(Baseline to end of double-blind period (estimated 32 months, maximum 5 years))
- Recurrent CV events (CV hospitalizations and urgent HF visits)(Baseline to end of double-blind period (estimated 32 months, maximum 5 years))
- Change from baseline in Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS)(Baseline to Month 30)