ZEUS - Effects of ziltivekimab for heart diseases and long term kidnet diseases
- Conditions
- Health Condition 1: I52- Other heart disorders in diseasesclassified elsewhere
- Registration Number
- CTRI/2021/10/037463
- Lead Sponsor
- ovo Nordisk AS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Open to Recruitment
- Sex
- Not specified
- Target Recruitment
- 0
General
1. 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.
2. Age above or equal to 18 years at the time of signing informed consent.
Disease specific
3. eGFR =15 and < 60 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) creatinine equation).a
4. Serum hs-CRP =2 mg/L at screening (visit 1).
5. Evidence of 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. =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. =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) = 0.90 at rest.
ii. Intermittent claudication with a =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).
a Laboratory results of eGFR for inclusion can be based on:
• measurements no more than 90 days old at screening, documented in medical records or
• measurements obtained the optional pre-screening visit (see Section 8.1), documented in
medical records or
• central laboratory measurement obtained at the screening visit (visit 1).24, 25
The subject must have been/be in usual health condition at the time of sample collection used for inclusion as evaluated by the investigator. See Appendix 2 for all requirements regarding clinical laboratory tests including requirements to creatinine assays and eGFR equations.
General
1. Known or suspected hypersensitivity to study intervention (s) or related products.
2. Previous participation in this study. Participation is defined as randomisation.
3. 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).
4. 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).
5. Any disorder, which in the investigator’s opinion might jeopardise participant’s safety or
compliance with the protocol.
6. Inadequate standard of care treatment which in the investigator’s opinion makes the
participant’s participation in the study inappropriate.
Laboratory values
7. Absolute neutrophil count <2×109/L at screening (visit 1).
8. Platelet count <120×109/L at screening (visit 1).
9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × upper limit of
normal at screening (visit 1).
10. HbA1c = 10% (= 86 mmol/mol)a Medical conditions
11. 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)).
12. Active hepatitis C (positive anti-HCV and detectable HCV RNA) or hepatitis B (positive
HBsAg) at screening (visit 1).
13. Current (or within 90 days of visit 1) chronic or intermittent haemodialysis or peritoneal
dialysis.
14. Clinical evidence of, or suspicion of, active infection at the discretion of the investigator.
15. History of recurrent serious infections (infections leading to hospitalisation or use of i.v.
antibiotics) in the 12 months prior to randomisation, at the discretion of the investigator.
16. History or evidence of untreated latent tuberculosis (TB) such as (but not limited to):
• History of a positive TB test or chest X-ray compatible with latent TB; and TB treatment
initiated less than 28 days prior to randomisation.
• 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.
17. History of gastrointestinal perforation. (Note: History of perforated appendicitis more than
5 years prior to screening (visit 1) is not exclusionary).
18. History of active diverticulitis in the 5 years prior to randomisation (visit 2).
19. History of inflammatory bowel disease that has been clinically active during the 12 months prior
to randomisation (visit 2).
20. Myocardial infarction, stroke, hospitalisation for unstable angina pectoris, or transient ischaemic
attack within 60 days prior to randomisation (visit 2).
21. Uncontrolled hypertension (defined as an average systolic blood pressure >180 mmHg or an
average diastolic blood pressure >110 mmHg) at screening (visit 1). (Note: Potential
participants may be retested for this criterion within the visit window and without rescreening, <br
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Time to first occurrence of 3-point MACE, a composite <br/ ><br>endpoint consisting of: <br/ ><br>• CV death <br/ ><br>• non-fatal MI <br/ ><br>• non-fatal strokeTimepoint: 2.5 years
- Secondary Outcome Measures
Name Time Method Time to first occurrence of expanded MACE, a composite <br/ ><br>endpoint consisting of: <br/ ><br>• CV deatha <br/ ><br>• non-fatal MI <br/ ><br>• non-fatal stroke <br/ ><br>• hospitalisation for unstable angina pectoris requiring <br/ ><br>urgent coronary revascularisation <br/ ><br>Timepoint: From randomisation (month 0) to <br/ ><br>end-of-study (up to 48 months)