Specifying the Anti-inflammatory Effects of Ziltivekimab

NCT ID: NCT06263244

Last Updated: 2025-10-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-03
• Study Completion Date: 2026-10-01

Brief Summary

The goal of this randomized, double blind, placebo controlled trial is to study whether ziltivekimab therapy reduces arterial wall inflammation as assessed by imaging, and reduces the systemic inflammatory tone as assessed by circulating monocytes, inflammatory biomarkers and proteomics.

Detailed Description

Considering that ziltivekimab is currently undergoing a phase 3 CVOT trial, it is of great importance to elucidate its mechanistic effects. The objective of this study is to research whether ziltivekimab therapy for 20 weeks reduces arterial wall inflammation, as assessed by state-of-the-art imaging modalities, and reduces systemic inflammatory tone, as assessed by in depth phenotyping of circulating monocytes, inflammatory biomarkers and proteomics. The imaging modalities used in this study are 68Ga-DOTATATE PET/CT and CCTA. This study is designed as a single center, randomized, double-blinded, placebo-controlled intervention study in 40 atherosclerotic patients of 50 years and older with hsCRP levels of 2 mg/L and above.

Conditions

Atherosclerosis; Inflammation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Ziltivekimab

15 mg ziltivekimab subcutaneously once per month for 5 months

Group Type: EXPERIMENTAL

Ziltivekimab

Intervention Type: DRUG

Monoclonal antibody targeting IL-6

Placebo

Placebo, subcutaneously, once per month for 5 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Ziltivekimab

Monoclonal antibody targeting IL-6

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

no other intervention name

Eligibility 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.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

E.S.stroes

Prof. dr. E.S.G. Stroes

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

E.S.G. Stroes, Prof.dr.

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Locations

Amsterdam UMC, location AMC

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Cheyenne Y.Y. Beverloo, MD

Role: CONTACT

c.y.beverloo@amsterdamumc.nl

+31205669111

Other Identifiers

NL83403.018.22

Identifier Type: -

Identifier Source: org_study_id