Ziltivekimab for lowering artery inflammation in people with coronary artery disease
Specifying the Anti-inflammatory Effects of Ziltivekimab With Diverse Imaging Modalities and In-depth Cellular Phenotyping
This trial will test whether 20 weeks of ziltivekimab lowers artery wall inflammation and systemic inflammatory markers in people aged 50 and older with multi-vessel coronary artery disease and elevated hsCRP.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 40 (estimated) |
| Ages | 50 Years to 85 Years |
| Sex | All |
| Sponsor | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Academic / other |
| Drugs / interventions | ziltivekimab |
| Locations | 1 site (Amsterdam) |
| Trial ID | NCT06263244 on ClinicalTrials.gov |
What this trial studies
This is a single-center, randomized, double-blind, placebo-controlled intervention in 40 patients aged 50+ with multi-vessel coronary artery disease and hsCRP ≥2 mg/L. Participants receive ziltivekimab or placebo for 20 weeks and undergo arterial imaging with 68Ga-DOTATATE PET/CT and coronary CT angiography (CCTA). The study also performs detailed phenotyping of circulating monocytes, inflammatory biomarkers, and proteomics to measure systemic inflammatory tone. Outcomes focus on changes in arterial wall inflammation on imaging and shifts in blood-based inflammatory signatures.
Who should consider this trial
Good fit: Ideal participants are adults aged 50 or older with multi-vessel coronary artery disease (CAD-RADS ≥2), hsCRP ≥2 mg/L, and who can attend visits at Amsterdam UMC while meeting safety lab criteria.
Not a fit: Patients with coronary stents in place, recent or active serious infections, severe autoimmune or chronic inflammatory disorders, uncontrolled diabetes, significant renal impairment, abnormal liver or platelet tests, or other listed exclusions are unlikely to qualify or benefit from this study.
Why it matters
Potential benefit: If successful, ziltivekimab could reduce arterial and systemic inflammation and potentially lower future cardiovascular risk.
How similar studies have performed: Previous ziltivekimab studies have demonstrated marked reductions in CRP and other inflammatory biomarkers, and the drug is currently being tested in a Phase 3 cardiovascular outcomes trial, so this mechanistic study builds on emerging clinical evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Aged 50 years and older. * Multi-vessel coronary artery disease (defined as CAD-RADS ≥2). * Serum hsCRP level ≥2 mg/L. Exclusion Criteria: * Coronary stents in situ. * Chronic or recent (\<1 month) (serious) infections and/or clinical signs of acute (serious) infection. * History of severe auto-immune diseases, or other (severe) (recurrent or chronic) inflammatory disorders. * Use of preventive systemic antibiotics (antibiotics used to treat latent tuberculosis are exempted). * Stable lipid lowering treatment for less than 4 weeks, including statins, ezetimibe and PCSK9 inhibition. * Untreated latent tuberculosis, active hepatitis B (positive HBsAg and/or positive anti-HBc with detectable HBV DNA) or C, human immunodeficiency virus (HIV) not on stable antiretroviral regimen * Uncontrolled diabetes (HbA1c \>90 mmol/mol). * Renal insufficiency, defined as eGFR \<45 ml/min/1.73 m2. * Platelet count \<120,000 and \>450,000 /mm3. * Elevated liver enzymes (\>3 ULN of liver transaminases), acute liver failure or known (severe) liver disease. * Premenopausal women not using birth-control. * History of gastrointestinal perforation, active diverticulitis (within 5 years) or active inflammatory bowel disease (within 12 months). * Uncontrolled hypertension (systolic \>180 mmHg; diastolic \>110 mmHg). * Diagnosis of (active) malignancy in last 5 years. * Standard contra-indications to 68Ga-DOTATATE PET, and CT based on physician's experience and current practices. * Inability or unwillingness to comply with the protocol requirements, or deemed by investigator to be unfit for the study.
Where this trial is running
Amsterdam
- Amsterdam UMC, location AMC — Amsterdam, Netherlands (Recruiting)
Study contacts
- Principal investigator: E.S.G. Stroes, Prof.dr. — Amsterdam UMC
- Study coordinator: Cheyenne Y.Y. Beverloo, MD
- Email: c.y.beverloo@amsterdamumc.nl
- Phone: +31205669111
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.