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

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ClinicalTrials.gov Identifier: NCT05021835
Recruitment Status : Recruiting
First Posted : August 26, 2021
Last Update Posted : April 30, 2024
Sponsor:
Information provided by (Responsible Party):
Novo Nordisk A/S

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Cardiovascular Risk Chronic Kidney Disease Inflammation Drug: Ziltivekimab B Drug: Ziltivekimab C Drug: Placebo (Ziltivekimab B) Drug: Placebo (Ziltivekimab C) Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ZEUS - Effects of Ziltivekimab Versus Placebo on Cardiovascular Outcomes in Participants With Established Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease and Systemic Inflammation
Actual Study Start Date : August 30, 2021
Estimated Primary Completion Date : September 24, 2025
Estimated Study Completion Date : January 29, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Kidney Diseases

Arms and Interventions
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Arm Intervention/treatment
Experimental: Ziltivekimab
Participants will receive 15 milligrams (mg) of either Ziltivekimab B or Ziltivekimab C subcutaneously using single-use pre-filled DV3430-C1 manual syringe or single-dose DV3430-C3 pen-injector respectively once monthly for up to 4 years.
 Drug: Ziltivekimab B
Administered subcutaneously (s.c., under skin) once-monthly using single-use pre-filled DV3430-C1 manual syringe and added to standard of care.

Drug: Ziltivekimab C
Administered subcutaneously (s.c., under skin) once-monthly using single-dose DV3430-C3 pen-injector and added to standard of care.
Placebo Comparator: Placebo
Participants will receive 15 mg of either placebo (Ziltivekimab B) or placebo (Ziltivekimab C) subcutaneously using single-use pre-filled DV3430-C1 manual syringe or single-dose DV3430-C3 pen-injector respectively once monthly for up to 4 years.
 Drug: Placebo (Ziltivekimab B)
Administered subcutaneously (s.c., under skin) once-monthly using single-use pre-filled DV3430-C1 manual syringe and added to standard of care.

Drug: Placebo (Ziltivekimab C)
Administered subcutaneously (s.c., under skin) once-monthly using single-dose DV3430-C3 pen-injector and added to standard of care.


Outcome Measures
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Primary Outcome Measures :
  1. Time to first occurrence of 3-point Major Adverse Cardiovascular Event (MACE), a composite endpoint consisting of: Cardiovascular (CV) death, non-fatal Myocardial Infarction (MI) and non-fatal stroke [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months) ]
    Months


Secondary Outcome Measures :
  1. Time to first occurrence of expanded MACE, a composite endpoint consisting of: CV death, non-fatal MI, non-fatal stroke and hospitalisation for unstable angina pectoris requiring urgent coronary revascularisation [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months) ]
    Months

  2. Number of heart failure hospitalisations or urgent heart failure visits or CV deaths [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months) ]
    Count

  3. Time to first occurrence of a composite kidney endpoint consisting of: CV death, onset of persistent atleast 40 percent (%) reduction in eGFR (CKD-epidemiology collaboration [CKD-EPI]) compared with baseline, kidney failure [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months) ]
    Months

  4. Time to occurrence of all-cause mortality [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months) ]
    Months

  5. Time to first occurrence of each of the individual components of the expanded MACE endpoint and the kidney composite endpoint. [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Months

  6. Time to first occurrence of MI (fatal and non-fatal). [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Months

  7. Time to first occurrence of stroke (fatal and non-fatal). [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Months

  8. Time to first occurrence of a composite MACE endpoint consisting of: all-cause mortality, non-fatal MI and non-fatal stroke [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Months

  9. Time to first occurrence of a 4-component kidney endpoint consisting of: onset of persistent at least 40% reduction in eGFR (CKD-EPI) compared with baseline, kidney failure [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Months

  10. Time to first occurrence of coronary revascularisation [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Months

  11. Change in Urinary Abumin-to-Ceatinine ratio (UACR). [ Time Frame: From randomisation (month 0) to 2 years (24 months). ]
    Percentage

  12. Change in eGFR (CKD-EPI)) [ Time Frame: From randomisation (month 0) to 2 years (24 months) ]
    mL/min/1.73 m^2

  13. Annual rate of change in eGFR (CKD-EPI) (total eGFR slope) [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    mL/min/1.73 m^2/ year

  14. Change in high-sensitivity C-reactive protein (hs-CRP) [ Time Frame: From randomisation (month 0) to 2 years (24 months ]
    Percentage

  15. Change in N-terminal-pro-brain natriuretic peptide ( NT-pro-BNP) [ Time Frame: From randomisation (month 0) to 2 years (24 months) ]
    Percentage

  16. Change in left ventricular ejection fraction (LVEF) [ Time Frame: From randomisation (month 0) to 2 years (24 months) ]
    Percentage

  17. Number of events of atrial fibrillation [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Count

  18. Change in haemoglobin [ Time Frame: From randomisation (month 0) to 2 years (24 months) ]
    Grams per deciliter (g/dL)

  19. Number of hospitalisations with infection as primary cause or death due to infection. [ Time Frame: From randomisation (month 0) to end-of-study (up to 48 months). ]
    Count

  20. Change in Short Form 36 (SF-36) Physical Component Score (PCS) [ Time Frame: From randomisation (month 0) to 2 years (24 months) ]
    Score on scale


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05021835


Contacts
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Contact: Novo Nordisk (+1) 866-867-7178 clinicaltrials@novonordisk.com

Locations
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Sponsors and Collaborators
Novo Nordisk A/S
Investigators
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Study Director: Clinical Transparency (dept. 2834) Novo Nordisk A/S
More Information
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Responsible Party: Novo Nordisk A/S
ClinicalTrials.gov Identifier: NCT05021835    
Other Study ID Numbers: EX6018-4758
U1111-1259-3422 ( Other Identifier: World Health Organization (WHO) )
2023-506926-35 ( Other Identifier: European Medical Agency (EMA) )
jRCT2021210033 ( Registry Identifier: JAPIC )
First Posted: August 26, 2021    Key Record Dates
Last Update Posted: April 30, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
URL: http://novonordisk-trials.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Kidney Diseases
Renal Insufficiency, Chronic
Cardiovascular Diseases
Inflammation
Chronic Disease
Pathologic Processes
Urologic Diseases
 Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Male Urogenital Diseases
Renal Insufficiency
Disease Attributes