ZEUS - Effects of ziltivekimab versus placebo on cardiovascular outcomes inparticipants with established atherosclerotic cardiovascular disease, chronickidney disease and systemic inflammation

Novo Nordisk41 个研究点分布在 1 个国家目标入组 6,200 人开始时间: 2021年8月12日最近更新: 2024年10月24日

试验速览

阶段: 3 期
状态: 已完成
发起方: Novo Nordisk
入组人数: 6,200
试验地点: 41
主要终点: Time to first occurrence of 3-point MACE, a composite

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

ZEUS is a study to demonstrate the superiority of ziltivekimab 15 mg s.c. once-monthly in reducing the risk of MACE (as defined by the primary endpoint) compared to placebo, both added to standard of care, in participants with established ASCVD, CKD and systemic inflammation.

This is an interventional, randomised, parallel-group, double-blind, placebo-controlled, multicentre, multi-national CVOT designed to evaluate the effects of 15 mg ziltivekimab versus placebo (randomised 1:1), both administered s.c. once-monthly and added to standard of care, on CV outcomes in participants with established ASCVD, CKD and systemic inflammation

研究设计

研究类型: Interventional
分配方式: Computer generated randomization
盲法: Double Blind Double Dummy

入排标准

年龄范围: 18.00 Year(s) 至 92.00 Year(s)（—）
性别: All

入选标准

•Informed consent obtained before any study-related activities.
•Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study, except for protocol described pre-screening activities which require a separate informed consent.
•Age above or equal to 18 years at the time of signing informed consent.
•Chronic kidney disease defined by one of the below: eGFR â‰¥ 15 and < 60 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)a UACR â‰¥ 200 mg/g and eGFR â‰¥ 60 mL/min/1.73 m2 (using the CKD-EPI creatinine equation).a
•Serum hs-CRP â‰¥ 2 mg/L.a
•Evidence of ASCVD by one or more of the following: a) Coronary heart disease defined as at least one of the following:
•Documented history of MI.
•Prior coronary revascularisation procedure.
•â‰¥50% stenosis in major epicardial coronary artery documented by cardiac catheterisation or CT coronary angiography.
•b) Cerebrovascular disease defined as at least one of the following:
•Prior stroke of atherosclerotic origin.
•Prior carotid artery revascularisation procedure.
•c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following:
•Intermittent claudication with an ankle-brachial index (ABI) â‰¤ 0.90 at rest.
•Intermittent claudication with a â‰¥50% stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound.
•Prior peripheral artery (excluding carotid) revascularisation procedure.
•Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g., trauma or osteomyelitis).
•a Laboratory results of eGFR3-5, UACR and hs-CRP for inclusion can be based on: measurements no more than 90 days old at screening, documented in medical records or measurements obtained at the optional pre-screening visit (see Section 8.1), documented in medical records or central laboratory measurement of eGFR, UACR or hs-CRP obtained at the screening visit (visit 1) or measurements from the prevalence study (NN6018-7527, FPFV expected Sep-2023) if nomore than 90 days old at screening.

排除标准

•Known or suspected hypersensitivity to study intervention (s) or related products.
•Previous participation in this study.
•Participation is defined as randomisation.
•Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using an adequate and highly effective contraceptive method (adequate contraceptive measures as required by local regulation or practice).
•Participation (i.e., signed informed consent) in any interventional clinical study of an approved or non-approved investigational medicinal product within 30 days prior to screening (visit 1).
•Any disorder, which in the investigatorâ€™s opinion might jeopardise participantâ€™s safety or compliance with the protocol.
•Inadequate standard of care treatment which in the investigatorâ€™s opinion makes the participantâ€™s participation in the study inappropriate.
•Laboratory values
•Absolute neutrophil count <2Ã—109/L at screening (visit 1).
•Platelet count <120Ã—109/L at screening (visit 1).
•Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 Ã— upper limit of normal at screening (visit 1).
•HbA1c â‰¥ 10% (â‰¥ 86 mmol/mol)a Medical conditions
•Diagnosis of human immunodeficiency virus (HIV) and not receiving a stable antiretroviral regimen, at the discretion of the investigator at screening (visit 1).
•(Note: for Argentina, see country specific requirements (Appendix 8, Section 10.8)).
•Active hepatitis C (positive anti-HCV and detectable HCV RNA) or hepatitis B (positive HBsAg and/or positive anti-HBc with detectable HBV DNA) at screening (visit 1).
•(Note: participants with positive anti-HBc and undetectable HBV DNA can be enrolled, see Section 8.3.7 for details).
•Current (or within 90 days of visit 1) chronic or intermittent haemodialysis or peritoneal dialysis.
•Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
•History of recurrent serious infections (infections leading to hospitalisation or use of i.v. antibiotics, i.v. antiviral or i.v. antifungal treatment) in the 12 months prior to randomisation, at the discretion of the investigator.
•Confirmed positive for latent TB at optional pre-screening visit or screening (visit 1) (see details in Section 8.3.6) and TB treatment initiated less than 28 days prior to randomisation.
•History of gastrointestinal perforation.
•(Note: History of perforated appendicitis more than 5 years prior to screening (visit 1) is not exclusionary).
•History of active diverticulitis in the 5 years prior to randomisation (visit 2).
•History of inflammatory bowel disease that has been clinically active during the 12 months prior to randomisation (visit 2).
•Myocardial infarction, stroke, hospitalisation for unstable angina pectoris, or transient ischaemic attack within 60 days prior to randomisation (visit 2).
•Planned coronary, carotid or peripheral artery revascularisation known on the day of randomisation (visit 2).
•Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure (thoracoscopic or laparoscopic) within the past 60 days prior to randomisation (visit 2) or any major surgical procedure planned at the time of randomisation (visit 2).
•Chronic heart failure classified as being in New York Heart Association (NYHA) Class IV at screening (visit 1).
•Presence or history of malignant neoplasms or in situ carcinomas (other than basal or squamous cell skin cancer, low risk prostate cancer, or in-situ carcinomas of the cervix, or carcinoma in situ/high grade prostatic intraepithelial neoplasia (PIN)) within 5 years prior to the day of screening (visit 1).
•History of bone marrow or solid organ transplant or anticipated to receive an organ transplant during the study (not including patients who have been in full remission following transplant at least 5 years and who are not receiving any immunosuppressive therapy).
•Prior or current medication
•Received a live or attenuated-live vaccine product within 4 weeks of study intervention administration (visit 2) or expected to receive a live or attenuated-live vaccine product during the treatment period.
•(Note: Not-live and not attenuated-live vaccines are not exclusionary.
•Use of preventive systemic antibiotics, systemic antivirals, or systemic antifungals at screening (visit 1).
•(Note: â€œSystemicâ€ is defined as oral or i.v. administered drugs that are absorbed into the circulation.
•Antibiotics used to treat latent TB are exempted).
•Use of systemic immunosuppressive drugs (both small molecules and biologics) or disease modifying anti-rheumatic drugs (DMARDs including both biologic DMARDs like anti-TNFalpha and conventional DMARDs like methotrexate) at screening (visit 1) or anticipated chronic use of such drugs any time during the study.
•(Note: Use of otic, ophthalmic, inhaled, and topical corticosteroids or local corticosteroid injections are not exclusionary.)
•a Laboratory results of HbA1c for inclusion can be based on: measurements no more than 90 days old at screening, documented in medical records or measurements from the optional pre-screening visit (see Section 8.1), documented in medical records or central laboratory measurement obtained at the screening visit (visit 1).
•The subject must have been/be in usual health condition at the time of sample collection used for inclusion as evaluated by the investigator.