ZEUS - A Research Study to Look at How Ziltivekimab Works Compared to Placebo in People With Cardiovascular Disease, Chronic Kidney Disease and Inflammation

Novo Nordisk

Status and phase: Enrolling; Phase 3

Conditions: Chronic Kidney Disease; Inflammation; Cardiovascular Risk

Treatments: Drug: Placebo (Ziltivekimab B); Drug: Placebo (Ziltivekimab C); Drug: Ziltivekimab C; Drug: Ziltivekimab B

Study type: Interventional

Funder types: Industry

Identifiers

NCT05021835

2023-506926-35 (Other Identifier)

jRCT2021210033 (Registry Identifier)

EX6018-4758

U1111-1259-3422 (Other Identifier)

Details and patient eligibility

About

This study is conducted to see if ziltivekimab reduces the risk of having cardiovascular events (for example heart attack and stroke) in people with cardiovascular disease, chronic kidney disease and inflammation.

Participants will either get ziltivekimab (active medicine) or placebo (a dummy medicine which has no effect on the body). This is known as the study medicine. Which treatment participants get is decided by chance. Participants chance of getting ziltivekimab or placebo is the same.

Ziltivekimab is not yet approved in any country or region in the world. It is a new medicine doctors cannot prescribe.

Participants will get the study medicine in a pre filled syringe. Participants will need to use the pre filled syringe to inject the study medicine into a skinfold once-monthly.

The study is expected to last for up to 4 years. Participants will have up to 20 clinic visits. Participants will have blood and urine samples taken at most of the clinic visits.

Participants will have their heart examined using sound waves (echocardiography) and electrodes (electrocardiogram).

Women cannot take part if pregnant, breast-feeding or planning to get pregnant during the study period.

Enrollment: 6,200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Chronic kidney disease defined by one of the below:

  1. Estimated glomerular filtration rate (eGFR) greater than or equal to (>=) 15 and below 60 mL/min/1.73 m^2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation)
  2. Urinary albumin-to-creatinine ratio (UACR) >= 200 milligrams per gram (mg/g) and eGFR >= 60 mL/min/1.73 m2 (using the CKD-EPI creatinine equation)

• Serum high-sensitivity C-reactive protein (hs-CRP) greater than or equal to 2 milligram per liter (mg/L)

• Evidence of atherosclerotic cardiovascular disease (ASCVD) by one or more of the following:

  a) Coronary heart disease defined as at least one of the following: i. Documented history of MI ii. Prior coronary revascularisation procedure iii. greater than or equal to 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: i. Prior stroke of atherosclerotic origin ii. Prior carotid artery revascularisation procedure iii. greater than or equal to 50% stenosis in carotid artery documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound.

  c) Symptomatic peripheral artery disease (PAD) defined as at least one of the following: i. Intermittent claudication with an ankle-brachial index (ABI) below or equal to 0.90 at rest ii. Intermittent claudication with a greater than or equal to 50% stenosis in peripheral artery (excluding carotid) documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound iii. Prior peripheral artery (excluding carotid) revascularisation procedure iv. Lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g. trauma or osteomyelitis).

Exclusion criteria

• Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
• 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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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6,200 participants in 2 patient groups, including a placebo group

Ziltivekimab

Experimental group

Description:

Participants will receive Ziltivekimab B or Ziltivekimab C subcutaneously once monthly for up to 4 years.

Treatment:

Drug: Ziltivekimab B

Drug: Ziltivekimab C

Placebo

Placebo Comparator group

Description:

Participants will receive either placebo (Ziltivekimab B) or placebo (Ziltivekimab C) subcutaneously once monthly for up to 4 years.

Treatment:

Drug: Placebo (Ziltivekimab C)

Drug: Placebo (Ziltivekimab B)