2025-522960-34-00招募中3 期
ZENITH: A Phase 3 Global, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Zilebesiran in Addition to Standard of Care in Reducing Major Adverse Cardiovascular Events in Adult Patients with Hypertension Not Adequately Controlled and With Either Established Cardiovascular Disease or High Risk for Cardiovascular Disease
Alnylam Pharmaceuticals Inc.43 个研究点 分布在 3 个国家目标入组 464 人开始时间: 2026年2月3日最近更新:
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 464
- 试验地点
- 43
- 主要终点
- 01. Time to first occurrence of a composite endpoint of CV death, nonfatal MI, nonfatal stroke, or HF event (hospitalization for HF or urgent HF visit).
研究概览
简要总结
- To evaluate whether zilebesiran compared to placebo reduces the risk of CV death, nonfatal MI, nonfatal stroke, or HF event (hospitalization for HF or urgent HF visit)
研究设计
- 分配方式
- Randomized
- 主要目的
- Double Blind (DB) treatment period
- 盲法
- Double (Subject, Monitor, Carer, Analyst, Investigator)
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
- 否
入选标准
- •Age at the time of initial informed consent as follows: a. 18 years or older for patients with established CVD b. 55 years or older for patients with high risk for CVD.
- •Established CVD or high risk for CVD: a. Established CVD defined as 1 or more of the following: Coronary artery disease, Cerebrovascular disease, Peripheral arterial disease OR b. High risk for CVD, defined by the presence of 2 or more of the following CV risk factors: i. Age ≥70 years at the time of initial informed consent ii. eGFR <60 mL/min/1.73m2 during screening iii. Urine albumin:creatinine ratio >300 mg/g during screening iv. Current smoker v. Atrial fibrillation on medical therapy (eg, anticoagulation or rate control) vi. Documented history of CAC with most recent CAC score >100 Agatston Units vii. NT-proBNP >125 pg/mL (15 pmol/L) during screening viii. Presence of 1 or both of the following (multiple events are counted as 1 total CV risk factor): • Type 1 or 2 diabetes mellitus • BMI ≥30 kg/m2 or ≥27 kg/m2 if the patient is of East Asian, Southeast Asian, or South Asian descent (eg, Chinese, Japanese, Korean, Indian, Pakistani, Thai)
- •Treated hypertension on stable therapy with a thiazide, thiazide-like, or loop diuretic and at least 1 other standard of care antihypertensive medication from the classes below. Fixed-dose combination medications will be considered as multiple medications based on their individual components. Stable therapy is defined as having no change in the prescription of antihypertensive medications or dosing regimens within 30 days prior to screening and during the Screening period. Antihypertensive medications must be prescribed consistent with guideline recommendations and/or local standards. If clinically appropriate, per Investigator discretion, patients not receiving a diuretic at the time of the Prescreening visit may have a thiazide or thiazide-like diuretic added before screening; patients must maintain this new antihypertensive regimen for at least 30 days prior to screening and during the Screening period to establish stability and should intend to continue this medication through the study period. a. ACE inhibitor or ARB b. CCB c. Beta blocker d. MRA e. Vasodilator (eg, hydralazine, minoxidil, alpha blocker) f. Centrally acting antihypertensive medication (eg, clonidine)
- •Seated automated mean office SBP ≥145 mmHg and <180 mmHg during the Screening period and ≥140 mmHg and <180 mmHg on Day 1 (before randomization) with measurements taken at least 7 days apart.
- •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
- •Known history of secondary hypertension (including, but not limited to, due to known history of renovascular hypertension, primary aldosteronism, pheochromocytoma, Cushing syndrome, or aortic coarctation). Hypertension secondary to CKD is not a criterion for exclusion.
- •Hemoglobin A1c (HbA1c) >10% within 60 days before screening or during the Screening period.
- •Known weight loss >10% in the 3 months before screening. Patients receiving drugs that have the potential to cause significant weight loss (eg, glucagon-like peptide-1 agonists) should be on a stable dose for at least 3 months before screening.
- •Hospitalization for HF within 60 days before screening or during the Screening period.
- •History of clinically significant CV event (eg, MI, stroke, revascularization procedure) within 60 days before screening or during the Screening period.
- •Known history of left ventricular ejection fraction <40% on most recent echocardiogram or equivalent imaging.
- •Severe aortic stenosis.
- •Has undergone major organ transplantation or is anticipated to undergo transplantation during the study.
- •Known medical history or evidence of liver cirrhosis.
- •Medical history that might limit the individual’s ability participate for the duration of the study (eg, severe respiratory disease; NYHA Class IV heart failure; cancer or evidence of spread within approximately the last 5 years, other than non-melanoma skin cancer).
- •For whatever reason, the Investigator believes the patient is not likely to be able to follow the protocol (eg, intolerance to SC injections or any excipient of the study drug) or the risk is likely greater than benefit from a persistent inhibitor of the RAS (eg, a patient with bilateral renal artery stenosis who developed renal failure following treatment with a RAS inhibitor).
- •Symptomatic orthostatic hypotension, defined as a fall of ≥20 mmHg SBP or ≥10 mmHg diastolic blood pressure (DBP) within approximately 1 to 3 minutes of standing up from a seated position by office blood pressure that is accompanied by symptoms (eg, dizziness, weakness, lightheadedness, or syncope) during screening.
- •Is not willing to comply with the contraceptive requirements during the study, as described in Section 5.10.1 of the Protocol.
- •Female patient is pregnant, planning a pregnancy, or breast-feeding.
- •Known history of alcohol use disorder or other substance abuse, within the last 12 months before screening, in the opinion of the Investigator
- •Blood pressure cannot be accurately assessed (eg, due to cuff size limitations).
- •Placed in an institution on the basis of an official or court order.
- •Has any of the following laboratory parameter assessments at screening: a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3×upper limit of normal (ULN). b. Total serum bilirubin >1.5×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 (patients on warfarin with an elevated INR will be allowed). d. Serum potassium >4.8 mEq/L (most recent value prior to randomization will be used for eligibility). e. eGFR <30 mL/min/1.73m2 (calculation will be based on the CKD Epidemiology Collaboration [CKD-EPI] equation)
- •Has known active human immunodeficiency virus (HIV) infection. Patients on antiretroviral therapy who are clinically stable and compliant with treatment for 6 months before screening per Investigator judgement are eligible for inclusion if they meet all of the inclusion criteria and none of the exclusion criteria.
- •Received an investigational agent within the last 30 days or 5 half-lives, whichever is longer, before the first dose of study drug. Any agent that has received health agency authorization (including for emergency use) by local or regional regulatory authorities is not considered investigational.
- •Currently taking both an ARB and an ACE inhibitor (either as single medications or part of combination medications such as ACE inhibitor/diuretic combinations or ARNIs that include an ARB).
- •Use of a potassium binder for the treatment of hyperkalemia within 3 months before screening and during the Screening period.
- •Currently taking, taken within 6 months before screening and during the Screening period, or anticipated to receive any therapeutic agent that targets AGT (approved or investigational) during the study Note: Patients who were in other zilebesiran clinical studies are eligible if it is known that they did not receive zilebesiran and they have completed their participation in the study.
- •Current or prior known history of severe intolerance to an ARB or ACE inhibitor other than cough (eg, angioedema, recurrent hyperkalemia, recurrent acute kidney injury), per Investigator judgement.
结局指标
主要结局
01. Time to first occurrence of a composite endpoint of CV death, nonfatal MI, nonfatal stroke, or HF event (hospitalization for HF or urgent HF visit).
01. Time to first occurrence of a composite endpoint of CV death, nonfatal MI, nonfatal stroke, or HF event (hospitalization for HF or urgent HF visit).
次要结局
- 01. Change from baseline in mean seated office SBP at Month 6
- 02. Time to first occurrence of a composite endpoint of CV death, nonfatal MI, or nonfatal stroke
- 03. Composite endpoint of CV death and total (first and subsequent) HF events (hospitalization for HF or urgent HF visit)
- 04. Time to first occurrence of composite endpoint of CV death, nonfatal MI, nonfatal stroke, or coronary revascularization
- 05. Time to all-cause death
研究者
Alnylam Clinical Trial Information Line
Scientific
Alnylam Pharmaceuticals Inc.
研究点 (43)
Loading locations...
相似试验
招募中
3 期
TRITON-CM: A Study to Evaluate Nucresiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy2024-519917-72-00Alnylam Pharmaceuticals Inc.676
招募中
2 期
A Study of DZD8586 in Adults With Primary Immune Thrombocytopenia (ITP) (TAI-SHAN11)NCT07294365Dizal Pharmaceuticals60
招募中
3 期
Comparison between rituximab plus zanubrutinib versus rituximab monotherapy in untreated splenic marginal zone lymphoma patients2023-503755-10-00Association International Extranodal Lymphoma Study Group90
招募中
3 期
A Placebo-Controlled Phase 3 Study to Evaluate the Effect of 10 mg Obicetrapib in Participants With Atherosclerotic Cardiovascular Disease
(ASCVD) Whose Current Treatment with Lipid-Modifying Therapies is not Sufficiently Effective.2023-507795-51-00NewAmsterdam Pharma B.V.4,094
招募中
2 期
Zasocitinib in Nonsegmental Vitiligo2025-522309-40-00Takeda Development Center Americas Inc.32