2024-518318-25-00招募中3 期
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)
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 441
- 试验地点
- 40
- 主要终点
- Composite outcome of all-cause mortality and recurrent CV events (CV hospitalizations and urgent heart failure [HF] visits) in both the overall population and the vutrisiran monotherapy subgroup (defined as patients not on tafamidis at study baseline).
研究概览
简要总结
To evaluate the efficacy of vutrisiran compared to placebo on reducing all-cause mortality and Cardiovascular (CV) events
研究设计
- 研究类型
- Interventional
- 分配方式
- Not Applicable
- 主要目的
- Follow-Up Period after the last dose of vutrisiran on study
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Age 18 to 85 years
- •Patient agrees to sign a separate medical records release form, where allowed by local regulations, to allow for the collection of information on vital status, cardiac transplant procedures, leftventricular assist device placement, and hospitalizations, for the duration of the DB Period of the study.
- •Documented diagnosis of ATTR amyloidosis with cardiomyopathy, classified as either hATTR amyloidosis with cardiomyopathy or wtATTR amyloidosis with cardiomyopathy
- •Medical history of HF with at least 1 prior hospitalization for HF (not due to arrhythmia or a conduction system disturbance treated with a permanent pacemaker) OR clinical evidence of HF (with or without hospitalization) manifested by signs and symptoms of volume overload or elevated intracardiac pressures (eg, elevated jugular venous pressure, shortness of breath or signs of pulmonary congestion on x-ray or auscultation, peripheral edema) that currently requires treatment with a diuretic.
- •Patient meets one of the following criteria: a. Tafamidis-naïve and not actively planning to commence treatment with tafamidis during the first 12 months following randomization (per exclusion criterion #7); or b. On tafamidis (Note: must be on-label use of commercial tafamidis per an approved cardiomyopathy indication and dose in the country of use)
- •Patient is clinically stable, with no CV-related hospitalizations within 6 weeks prior to randomization, as assessed by the Investigator.
- •Screening 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.
- •Able to complete ≥150 meters on the 6-MWT at Screening.
- •Have a Karnofsky performance status of ≥60%.
- •Patient is able to understand and is willing and able to comply with the study requirements and to provide written informed consent.
排除标准
- •Has known primary amyloidosis(AL amyloidosis)or leptomeningeal amyloidosis
- •Has persistent elevation of systolic (>170 mmHg) or diastolic (>100 mmHg) blood pressure that is considered uncontrolled by physician
- •NYHA Class IV heart failure; or NYHA Class III heart failure AND ATTR Amyloidosis Disease Stage 3 (defined as NT-proBNP >3000 ng/L and eGFR <45 ml/min)
- •Has untreated hypo- or hyperthyroidism
- •Has an active infection requiring systemic antiviral, antiparasitic or antimicrobial therapy that will not be completed prior to dosing (Day 1)
- •Prior or anticipated (during the first 12 months after randomization) heart, liver or other organ transplant or implantation of left-ventricular assist device
- •History of multiple drug allergies; or history of allergic reaction to any component of or excipient in the study drug
- •History of intolerance to SC injection(s) or significant abdominal scarring that could potentially hinder study drug administration or evaluation of local tolerability
- •Has other medical conditions or comorbidities which, in the opinion of the Investigator, would interfere with study compliance or data interpretation
- •Is not willing to comply with the contraceptive requirements during the study period
- •Female patient is pregnant, planning a pregnancy, or breast-feeding
- •Currently taking doxycycline, ursodeoxycholic acid or tauroursodeoxycholic acid; if previously on any of these agents, must have completed a 30-day wash-out prior to dosing (Day 1)
- •Unwilling or unable to limit alcohol consumption throughout the course of the study
- •History of alcohol abuse, within the last 12 months before Screening, in the opinion of the Investigator
- •Has a polyneuropathy disability (PND) Score IIIa, IIIb, or IV (requires cane or stick to walk due to polyneuropathy, or is wheelchair bound) at the Screening visit
- •30.History of illicit drug abuse within the past 5 years that in the opinion of the Investigator would interfere with compliance with study procedures or follow-up visits
- •Has any of the following laboratory parameter assessments at Screening: a. AST or ALT levels >2.0 × ULN; b. Total bilirubin >2.0 × ULN. Patients with elevated total bilirubin that is secondary to documented Gilbert's syndrome are eligible if the total bilirubin is <2 × ULN); c. International normalized ratio (INR) >1.5 (unless patients were on anticoagulant therapy in which case excluded if INR >3.5)
- •Has eGFR <30 mL/min/1.73 m2 (using the modification of diet in renal disease [MDRD] formula) at Screening
- •Has known human immunodeficiency virus infection; or evidence of current or chronic hepatitis C virus or hepatitis B virus infection
- •Tafamidis-naïve patients (per inclusion criterion #4a) for whom the Investigator actively plans or anticipates commencing treatment with tafamidis either during the Screening Period or the first 12 months following randomization, taking into consideration clinical status, patient preference and/or commercial availability of tafamidis
- •Received prior TTR-lowering treatment (including revusiran, patisiran or inotersen) or participated in a gene therapy trial for hATTR amyloidosis
- •Currently taking diflunisal; if previously on this agent, must have at least a 30-day wash-out prior to dosing (Day 1)
- •Unwilling to avoid any concurrent treatment with diflunisal, ursodeoxycholic acid/tauroursodeoxycholate/doxycycline, or TTR lowering agents (eg, patisiran, inotersen)
- •Current or future participation in another investigational device or drug study, scheduled to occur during this study, or has received an investigational agent or device within 30 days (or 5 half-lives of the investigational drug, whichever is longer) prior to dosing (Day 1). In the case of investigational TTR stabilizer drugs, washout for 3 months prior to dosing (Day 1) is required; this does not apply to patients who are on tafamidis at baseline (inclusion criterion #4)
- •Requires treatment with or is unwilling to avoid any concurrent treatment with nondihydropyridine calcium channel blockers (eg, verapamil, diltiazem)
- •Other non-TTR cardiomyopathy, hypertensive cardiomyopathy, cardiomyopathy due to valvular heart disease, or cardiomyopathy due to ischemic heart disease (eg, prior myocardial infarction with documented history of cardiac enzymes and ECG changes) that the Investigator feels is a significant contributor or the predominant cause of the patient's heart failure
- •Unstable congestive heart failure (CHF) (including patients who require adjustment of existing diuretics or addition of new diuretics at time of Screening for purposes of achieving optimal management of CHF)
- •Had acute coronary syndrome or unstable angina within the past 3 months
- •Has history of sustained ventricular tachycardia or aborted ventricular fibrillation
- •Has history of atrioventricular nodal or sinoatrial nodal dysfunction for which a pacemaker is indicated but will not be placed
结局指标
主要结局
Composite outcome of all-cause mortality and recurrent CV events (CV hospitalizations and urgent heart failure [HF] visits) in both the overall population and the vutrisiran monotherapy subgroup (defined as patients not on tafamidis at study baseline).
Composite outcome of all-cause mortality and recurrent CV events (CV hospitalizations and urgent heart failure [HF] visits) in both the overall population and the vutrisiran monotherapy subgroup (defined as patients not on tafamidis at study baseline).
次要结局
- The following secondary endpoints will be defined in both the overall population and the vutrisiran monotherapy subgroup: - Change from baseline in 6-minute walk test (6-MWT) - Change from baseline in the Kansas City Cardiomyopathy QuestionnaireOverall Summary (KCCQ-OS) - All-cause mortality - Change from baseline in NYHA Class
研究者
Clinical Trials Information Line
Scientific
Alnylam Pharmaceuticals Inc.
研究点 (40)
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