Atherosclerotic cardiovascular disease Chronic kidney disease Systemic inflammation MedDRA version: 26.0 Level: LLT Classification code 10051615 Term: Atherosclerotic cardiovascular disease System Organ Class: 100000004866 MedDRA version: 23.1 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.1 Level: LLT Classification code 10067394 Term: hs-CRP increased System Organ Class: 100000004848 MedDRA
Conditions
Interventions
Product Name: Ziltivekimab B 15 mg/mL DV3430-C1
Pharmaceutical Form: Solution for injection
INN or Proposed INN: N/A
Other descriptive name: Ziltivekimab
Concentration unit: mg/ml milligram(s)/millili
Sponsors
Novo Nordisk A/S
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Chronic kidney disease defined by one of the below: - 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) - UACR above or equal to 200 mg/g and eGFR above or equal to 60 mL/min/1.73 m2 (using the CKD-EPI creatinine equation). - Serum hs-CRP greater than or equal to 2 mg/L - 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. 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). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4950
Exclusion criteria
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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: - To demonstrate the superiority of ziltivekimab 15 mg s.c. once-monthly compared to placebo, both added to standard of care, in participants with established ASCVD, CKD and systemic inflammation, with regards to the following: •reducing the risk of expanded MACE (as defined by the confirmatory secondary endpoint) •reducing the risk of heart failure (as defined by the confirmatory secondary endpoint) •reducing all-cause mortality •delaying the progression of CKD (as defined by the confirmatory secondary endpoint) - To compare the effects of ziltivekimab 15 mg s.c. once-monthly versus placebo, both added to standard of care, in participants with established ASCVD, CKD and systemic inflammation, with regards to the following: •reducing systemic inflammation (defined by the secondary and exploratory endpoints) •improving patient reported outcomes (PRO) •not increasing severe infections (as defined by secondary safety endpoints);Primary end point(s): 1. Time to first occurrence of 3-point MACE, a composite endpoint consisting of: - CV death ( Based on EAC-confirmed events, including undetermined cause of death) - non-fatal MI ( Based on EAC-confirmed events, acute MI only) - non-fatal stroke ( Based on EAC-confirmed events, including ischaemic, haemorrhagic and undetermined stroke);Timepoint(s) of evaluation of this end point: 1. From randomisation (month 0) to end-of-study (up to 48 months (Maximum treatment duration is dependent on event rates and is estimated to be approximately 48 months including a 3-month follow-up period) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Time to first occurrence of expanded MACE, a composite endpoint consisting of: - CV death (Based on EAC-confirmed events, including undetermined cause of death) - non-fatal MI ( Based on EAC-confirmed events, acute MI only) - non-fatal stroke ( Based on EAC-confirmed events, including ischaemic, haemorrhagic and undetermined stroke) - hospitalisation for unstable angina pectoris requiring urgent coronary revascularisation ( Based on EAC-confirmed events) 2. Number of hospitalisations for heart failure (Based on EAC-confirmed events) or urgent heart failure visit (Based on EAC-confirmed events) or CV deaths (Based on EAC-confirmed events, including undetermined cause of death) 3. Time to occurrence of all-cause mortality (Based on EAC-confirmed events) 4. Time to first occurrence of a composite CKD endpoint consisting of: - onset of persistent (“Persistent” is defined as 2 consecutive samples meeting the criteria. The 2 samples must be at least 4 weeks apart) greater than or equal to 40% reduction in eGFR (CKD-EPI) compared with baseline - kidney failure defined as: a) death from kidney failure (Based on EAC-confirmed events, defined as a non-CV death that is due to the direct consequences of severely impaired kidney function. Undetermined cause of death in participants with eGFR below15 mL/min/1.73 m^2 will be considered kidney death) b) onset of persistent (“Persistent” is defined as 2 consecutive samples meeting the criteria. The 2 samples must be at least 4 weeks apart) eGFR below 15 mL/min/1.73 m^2 (CKD-EPI) c) initiation of chronic kidney replacement therapy (maintenance dialysis or kidney transplantation) (Based on EAC-confirmed events) 5. Time to first occurrence of each of the individual components (Based on EAC-confirmed events) of the expanded MACE endpoint and the kidney composite endpoint 6. Time to first occurrence of MIs (acute MI only) (fatal and non-fatal) (Based on EAC-confirmed events) 7. Time to first occurrence | — |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czech Republic, Denmark, European Union, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Poland, Portugal, Romania, Russian Federation, Serbia, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Transparency (2834)
Novo Nordisk A/S
Outcome results
None listed