ZILTIVEKIMAB for Atherosclerotic cardiovascular disease | Chronic kidney disease | Systemic inflammation

Inclusion criteria

• {"criterion_text":"-Chronic kidney disease defined by one of the below: eGFR ≥15 and < 60 mL/min/1.73 m2 (using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation), OR UACR ≥200 mg/g and eGFR ≥60 mL/min/1.73 m2 (using the CKD-EPI creatinine equation)."}
• {"criterion_text":"-Serum hs-CRP ≥2 mg/L"}
• {"criterion_text":"-Evidence of ASCVD by one or more of the following: Coronary heart disease defined as at least one of the following: Documented history of MI, prior coronary revascularisation procedure, or ≥50% stenosis in major epicardial coronary artery documented by cardiac catheterisation or CT coronary angiography. Cerebrovascular disease defined as at least one of the following: Prior stroke of atherosclerotic origin, prior carotid artery revascularisation procedure, or ≥50% stenosis in carotid artery documented by X-ray angiography, MR angiography, CT angiography or Doppler ultrasound. Symptomatic peripheral artery disease (PAD) defined as at least one of the following: Intermittent claudication with an ankle-brachial index (ABI) ≤ 0.90 at rest, intermittent claudication with a ≥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, or lower extremity amputation at or above ankle due to atherosclerotic disease (excluding e.g., trauma or osteomyelitis)."}

Exclusion criteria

• {"criterion_text":"-Clinical evidence of, or suspicion of, active infection at the discretion of the investigator."}
• {"criterion_text":"-Myocardial infarction, stroke, hospitalisation for unstable angina pectoris, or transient ischaemic attack within 60 days prior to randomisation (visit 2)."}
• {"criterion_text":"-Planned coronary, carotid or peripheral artery revascularisation known on the day of randomisation (visit 2)."}
• {"criterion_text":"-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)."}
• {"criterion_text":"-Clinical evidence of, or suspicion of, active infection at the discretion of the investigator."}

Primary endpoints

• {"endpoint_text":"-Time to first occurrence of 3-point MACE, a composite endpoint consisting of CV death, non-fatal MI, and non-fatal stroke. Measured from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of 3-point MACE, a composite endpoint consisting of CV death, non-fatal MI, and non-fatal stroke. Measured from randomisation to end-of-study."}

Secondary endpoints

• {"endpoint_text":"-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. Measured from randomisation to end-of-study.","definition_or_measurement_approach":"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. Measured from randomisation to end-of-study."}
• {"endpoint_text":"-Number of heart failure hospitalisations or urgent heart failure visits or CV deaths from randomisation to end-of-study.","definition_or_measurement_approach":"Number of heart failure hospitalisations or urgent heart failure visits or CV deaths from randomisation to end-of-study."}
• {"endpoint_text":"-Time to first occurrence of a composite kidney endpoint consisting of CV death, onset of persistent ≥ 40% reduction in eGFR (CKD-EPI) compared with baseline and kidney failure defined as death from kidney failure, onset of persistent eGFR< 15 mL/min/1.73 m2 (CKD-EPI), or initiation of chronic kidney replacement therapy. Measured from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of a composite kidney endpoint consisting of CV death, onset of persistent ≥ 40% reduction in eGFR (CKD-EPI) compared with baseline and kidney failure defined as death from kidney failure, onset of persistent eGFR< 15 mL/min/1.73 m2 (CKD-EPI), or initiation of chronic kidney replacement therapy. Measured from randomisation to end-of-study."}
• {"endpoint_text":"-Time to occurrence of all-cause mortality from randomisation to end-of-study.","definition_or_measurement_approach":"Time to occurrence of all-cause mortality from randomisation to end-of-study."}
• {"endpoint_text":"-Time to first occurrence of each of the individual components of the expanded MACE endpoint and the kidney composite endpoint from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of each of the individual components of the expanded MACE endpoint and the kidney composite endpoint from randomisation to end-of-study."}
• {"endpoint_text":"-Time to first occurrence of MIs (fatal and non-fatal) from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of MIs (fatal and non-fatal) from randomisation to end-of-study."}
• {"endpoint_text":"-Time to first occurrence of stroke (fatal and non-fatal) from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of stroke (fatal and non-fatal) from randomisation to end-of-study."}
• {"endpoint_text":"-Time to first occurrence of a composite MACE endpoint consisting of all-cause mortality, non-fatal MI, and non-fatal stroke. Measured from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of a composite MACE endpoint consisting of all-cause mortality, non-fatal MI, and non-fatal stroke. Measured from randomisation to end-of-study."}
• {"endpoint_text":"-Time to first occurrence of a 4-component kidney endpoint consisting of onset of persistent ≥ 40% reduction in eGFR (CKD-EPI) compared with baseline, and kidney failure defined as death from kidney failure, onset of persistent eGFR< 15 mL/min/1.73 m2 (CKD-EPI), or initiation of chronic kidney replacement therapy. Measured from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of a 4-component kidney endpoint consisting of onset of persistent ≥ 40% reduction in eGFR (CKD-EPI) compared with baseline, and kidney failure defined as death from kidney failure, onset of persistent eGFR< 15 mL/min/1.73 m2 (CKD-EPI), or initiation of chronic kidney replacement therapy. Measured from randomisation to end-of-study."}
• {"endpoint_text":"-Time to first occurrence of coronary revascularisation from randomisation to end-of-study.","definition_or_measurement_approach":"Time to first occurrence of coronary revascularisation from randomisation to end-of-study."}
• {"endpoint_text":"-Change in UACR from randomisation to 2 years.","definition_or_measurement_approach":"Change in UACR from randomisation to 2 years."}
• {"endpoint_text":"-Change in eGFR (CKD-EPI) from randomisation to 2 years.","definition_or_measurement_approach":"Change in eGFR (CKD-EPI) from randomisation to 2 years."}
• {"endpoint_text":"-Annual rate of change in eGFR (CKD-EPI) (total eGFR slope) from randomisation to end-of-study.","definition_or_measurement_approach":"Annual rate of change in eGFR (CKD-EPI) (total eGFR slope) from randomisation to end-of-study."}
• {"endpoint_text":"-Change in hs-CRP from randomisation to 2 years.","definition_or_measurement_approach":"Change in hs-CRP from randomisation to 2 years."}
• {"endpoint_text":"-Change in NT-pro-BNP from randomisation to 2 years.","definition_or_measurement_approach":"Change in NT-pro-BNP from randomisation to 2 years."}
• {"endpoint_text":"-Change in left ventricular ejection fraction (LVEF) from randomisation to 2 years.","definition_or_measurement_approach":"Change in left ventricular ejection fraction (LVEF) from randomisation to 2 years."}
• {"endpoint_text":"-Number of events of atrial fibrillation from randomisation to end-of-study.","definition_or_measurement_approach":"Number of events of atrial fibrillation from randomisation to end-of-study."}
• {"endpoint_text":"-Change in haemoglobin from randomisation to 2 years.","definition_or_measurement_approach":"Change in haemoglobin from randomisation to 2 years."}
• {"endpoint_text":"-Number of hospitalisations with infection as primary cause or death due to infection from randomisation to end-of-study.","definition_or_measurement_approach":"Number of hospitalisations with infection as primary cause or death due to infection from randomisation to end-of-study."}
• {"endpoint_text":"-Change in Short Form 36 (SF-36) Physical Component Score (PCS) from randomisation to 2 years.","definition_or_measurement_approach":"Change in Short Form 36 (SF-36) Physical Component Score (PCS) from randomisation to 2 years."}

Methods

• Direct to patient via Marken Limited (direct-to-patient recruitment/retention and direct-to-patient service supplier)

Primary sponsor

Full Name

Novo Nordisk A/S

Organisation Type

Pharmaceutical company

Country Of Registered Address

Denmark

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Various operational CRO roles including lost-to-follow-up supplier, event adjudication supplier, imaging supplier (as listed in third-party duties)

Name

IQVIA Limited

Responsibilities

Special Laboratory

Name

DaVita Clinical Research Deutschland GmbH

Third parties

• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Lost to follow-up supplier; (also listed with other sponsor duties such as event adjudication supplier, imaging supplier in other entries)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translation Services Supplier","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Affidea Piraeus Biopathological","duties_or_roles":"CCTA","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Oracle America Inc.","duties_or_roles":"CRF supplier","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Qualitymetric Incorporated LLC","duties_or_roles":"Patient Reported Outcome (ePRO)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Perceptive Eclinical Limited","duties_or_roles":"IWRS supplier","organisation_type":"Pharmaceutical company"}
• {"country":"Greece","full_name":"Bioiatriki Private Medical Polyclinic S.A.","duties_or_roles":"CRP high-sensitivity test, Coronary computed tomography angiography","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United States","full_name":"Medable Inc.","duties_or_roles":"Participants Application","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Special Laboratory","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Marken Limited","duties_or_roles":"Direct to patient","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Oracle Danmark ApS","duties_or_roles":"Global Safety Database supplier","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"International Drug Development Institute","duties_or_roles":"Independent External statistical Supplier","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Caristo Diagnostics Ltd","duties_or_roles":"CT-scan analysis vendor","organisation_type":"SME"}
• {"country":"United States","full_name":"The Brigham And Women’s Hospital Inc.","duties_or_roles":"Optional future echocardiographic biobank","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Ireland","full_name":"IQVIA Limited","duties_or_roles":"Imaging Supplier","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medable Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Marken Limited","duties_or_roles":"Direct to patient","organisation_type":"Pharmaceutical company"}