Effect of Secukinumab on Cardiorenal Outcomes in Patients With Cardiorenal Metabolic Syndrome and Atherosclerotic Cardiovascular Disease

Inclusion criteria

• Age ≥ 18 years at screening.
• Meet at least one metabolic abnormality:

• Body mass index ≥ 23 kg/m²;
• Waist circumference ≥ 80 cm (female) or ≥ 90 cm (male);
• Fasting glucose 100-124 mg/dL (5.6-6.9 mmol/L) or glycated hemoglobin (HbA1c) 5.7-6.4%;
• Serum triglycerides ≥ 3.51 mmol/L;
• Documented hypertension, metabolic syndrome, or diabetes mellitus.
• Meet at least one diagnostic criterion for chronic kidney disease:

• eGFR ≥15 and <60 mL/min/1.73 m² (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation);
• UACR ≥ 200 mg/g with eGFR ≥ 60 mL/min/1.73 m² and documented albuminuria.
• Have documented atherosclerotic cardiovascular disease (at least one):

• Coronary heart disease: history of myocardial infarction, prior coronary revascularization, or ≥50% major epicardial coronary artery stenosis confirmed by cardiac catheterization or coronary coronary computed tomography angiography (CTA);
• Cerebrovascular disease: prior atherosclerotic stroke, prior carotid revascularization, or ≥50% carotid artery stenosis confirmed by imaging;
• Symptomatic peripheral artery disease.
• Able and willing to provide written informed consent.

Exclusion criteria

• Clinical evidence or suspected active infection judged by investigators.
• History of myocardial infarction, stroke, transient ischemic attack, or hospitalization for unstable angina within 60 days prior to randomization.
• Planned coronary, carotid, or peripheral artery revascularization at randomization.
• Major cardiac surgery, non-cardiac major surgery, or major endoscopy within 60 days before randomization, or planned major surgery during the study period.
• Current use of systemic immunosuppressive agents (glucocorticoids, small-molecule immunosuppressants, biologic DMARDs, anti-tumor drugs).
• Long-term intermittent hemodialysis or peritoneal dialysis.
• History or confirmed evidence of active tuberculosis.
• History of inflammatory bowel disease.
• Active malignancy or carcinoma in situ within the past 5 years.
• Uncontrolled hypertension (systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg).
• Chronic heart failure classified as New York Heart Association (NYHA) Class IV.
• History of bone marrow or solid organ transplantation, or planned organ transplantation during the study.
• Known or suspected allergy to secukinumab or related excipients.
• Pregnant, lactating females, or females of childbearing potential without adequate effective contraception.
• Absolute neutrophil count <2 ×10⁹/L or platelet count <120 ×10⁹/L, or alanine aminotransferase (ALT) / aspartate aminotransferase (AST) >2.5 × upper limit of normal.
• HbA1c ≥10% (≥86 mmol/mol).
• Any disease condition that may endanger subject safety or impair protocol compliance per investigator judgment.
• Subjects with inadequate standard therapy judged by investigators.