Atherosclerotic Cardiovascular Disease, Cardiorenal Metabolic Syndrome, Carotid Artery Stenosis, Chronic Kidney Disease, Coronary Artery Disease, Hypertension, Peripheral Arterial Disease, Type 2 Diabetes Mellitus
Conditions
Brief summary
This is a prospective, randomized, open-label, parallel-controlled clinical trial to evaluate the efficacy and safety of targeted IL-17A inhibition with secukinumab on cardiovascular and renal endpoints in 100 patients with cardiorenal metabolic syndrome and atherosclerotic cardiovascular disease (ASCVD). Eligible subjects will be randomized 1:1 to receive either secukinumab 75 mg subcutaneous injection every 4 weeks for a total of 12 weeks plus standard guideline-directed medical therapy, or standard medical therapy alone. The primary endpoint is the time to first occurrence of 3-point major adverse cardiovascular events (MACE, including cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) over a 2-year follow-up period. Key indicators include estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) for renal outcome assessment.
Interventions
BIOLOGICALSecukinumab (75 mg)
75 mg, subcutaneous injection, once every 4 weeks for a total of 12 weeks
OTHERStandard Medical Therapy
Standard guideline-directed cardiovascular and renal protective therapy per clinical practice guidelines
Sponsors
Peking University Third Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years at screening. 2. Meet at least one metabolic abnormality: 1. Body mass index ≥ 23 kg/m²; 2. Waist circumference ≥ 80 cm (female) or ≥ 90 cm (male); 3. Fasting glucose 100-124 mg/dL (5.6-6.9 mmol/L) or glycated hemoglobin (HbA1c) 5.7-6.4%; 4. Serum triglycerides ≥ 3.51 mmol/L; 5. Documented hypertension, metabolic syndrome, or diabetes mellitus. 3. Meet at least one diagnostic criterion for chronic kidney disease: 1. eGFR ≥15 and \<60 mL/min/1.73 m² (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] creatinine equation); 2. UACR ≥ 200 mg/g with eGFR ≥ 60 mL/min/1.73 m² and documented albuminuria. 4. Have documented atherosclerotic cardiovascular disease (at least one): 1. 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); 2. Cerebrovascular disease: prior atherosclerotic stroke, prior carotid revascularization, or ≥50% carotid artery stenosis confirmed by imaging; 3. Symptomatic peripheral artery disease. 5. Able and willing to provide written informed consent.
Exclusion criteria
1. Clinical evidence or suspected active infection judged by investigators. 2. History of myocardial infarction, stroke, transient ischemic attack, or hospitalization for unstable angina within 60 days prior to randomization. 3. Planned coronary, carotid, or peripheral artery revascularization at randomization. 4. Major cardiac surgery, non-cardiac major surgery, or major endoscopy within 60 days before randomization, or planned major surgery during the study period. 5. Current use of systemic immunosuppressive agents (glucocorticoids, small-molecule immunosuppressants, biologic DMARDs, anti-tumor drugs). 6. Long-term intermittent hemodialysis or peritoneal dialysis. 7. History or confirmed evidence of active tuberculosis. 8. History of inflammatory bowel disease. 9. Active malignancy or carcinoma in situ within the past 5 years. 10. Uncontrolled hypertension (systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg). 11. Chronic heart failure classified as New York Heart Association (NYHA) Class IV. 12. History of bone marrow or solid organ transplantation, or planned organ transplantation during the study. 13. Known or suspected allergy to secukinumab or related excipients. 14. Pregnant, lactating females, or females of childbearing potential without adequate effective contraception. 15. 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. 16. HbA1c ≥10% (≥86 mmol/mol). 17. Any disease condition that may endanger subject safety or impair protocol compliance per investigator judgment. 18. Subjects with inadequate standard therapy judged by investigators.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to First Occurrence of 3-point Major Adverse Cardiovascular Events (MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) | From randomization up to 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Time to first extended MACE composite endpoint | From randomization up to 2 years |
| Total number of heart failure hospitalizations, urgent heart failure visits or cardiovascular death | From randomization up to 2 years |
| All-cause mortality | From randomization up to 2 years |
| Changes in carotid artery stenosis degree | Baseline, Month 6, Month 24 |
| Changes in carotid artery plaque size | Baseline, Month 6, Month 24 |
| Time to composite chronic kidney disease endpoint (sustained eGFR decline ≥30% or kidney failure) | From randomization up to 2 years |
| Incidence of kidney failure (death due to renal failure, sustained eGFR <15 mL/min/1.73 m², or long-term renal replacement therapy) | From randomization up to 2 years |
| Changes in UACR | Baseline, Month 6, Month 24 |
| Changes in eGFR | Baseline, Month 6, Month 24 |
| Annual slope of eGFR | Baseline, Month 6, Month 24 |
| Changes in high-sensitivity C-reactive protein (hs-CRP) | Baseline, Month 6, Month 24 |
| Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) | Baseline, Month 6, Month 24 |
| Number of new-onset atrial fibrillation events | From randomization up to 2 years |
| Changes in hemoglobin levels | Baseline, Month 6, Month 24 |
Contacts
CONTACTWen Tang, MD, PhD
Outcome results
None listed