Clinical trial NCT06263244: Specifying the Anti-inflammatory Effects of Ziltivekimab
Official title: Specifying the Anti-inflammatory Effects of Ziltivekimab With Diverse Imaging Modalities and In-depth Cellular Phenotyping
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Atherosclerosis
Inflammation
Keywords: DOTATATE
Ziltivekimab
Inflammation
Monocytes
CCTA
PET/CT
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2024-02-16
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, double blind, placebo-controlled trial
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: TBRmax coronary arteries
timeFrame: 5.5 months
measure: monocyte activation marker protein expression
timeFrame: 5.5 months
Secondary outcomes:
measure: delta PCAT
timeFrame: 5.5 months
measure: Correlation delta TBRmax and CCTA derived plaque characteristics
timeFrame: 5.5 months
measure: delta SUVmax bone marrow
timeFrame: 5.5 months
measure: delta TBRmax ascending aorta
timeFrame: 5.5 months
measure: changes monocyte phenotype
timeFrame: 5.5 months
measure: changes in hsCRP
timeFrame: 5.5 months
measure: changes plasma cytokine and chemokine levels (pg/mL)
timeFrame: 5.5 months
measure: changes plasma cytokine and chemokine levels (ng/mL)
timeFrame: 5.5 months
Other outcomes:
Locations:
Study officials:
affiliation: Amsterdam UMC
name: E.S.G. Stroes, Prof.dr.
role: PRINCIPAL_INVESTIGATOR
References: