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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
40
Monoclonal antibody targeting IL-6
Placebo
Amsterdam UMC, location AMC
Amsterdam, Netherlands
TBRmax coronary arteries
mean percentage change in coronary arteries target to background ratio (TBRmax)
Time frame: 5.5 months
monocyte activation marker protein expression
The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16.
Time frame: 5.5 months
delta PCAT
Difference in PCAT (CCTA derived) after ziltivekimab treatment.
Time frame: 5.5 months
Correlation delta TBRmax and CCTA derived plaque characteristics
Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA.
Time frame: 5.5 months
delta SUVmax bone marrow
Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment.
Time frame: 5.5 months
delta TBRmax ascending aorta
Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment
Time frame: 5.5 months
changes monocyte phenotype
The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile.
Time frame: 5.5 months
changes in hsCRP
hsCRP (high-sensitivity C-reactive protein): mg/L
Time frame: 5.5 months
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changes plasma cytokine and chemokine levels (pg/mL)
TNF-α (Tumor Necrosis Factor alpha): pg/mL IL-8 (Interleukin-8): pg/mL MCP-1 (Monocyte Chemoattractant Protein-1): pg/mL
Time frame: 5.5 months
changes plasma cytokine and chemokine levels (ng/mL)
sICAM (soluble Intercellular Adhesion Molecule): ng/mL sVCAM (soluble Vascular Cell Adhesion Molecule): ng/mL
Time frame: 5.5 months