Specifying the Anti-inflammatory Effects of Ziltivekimab

Inflammation Clinical Trial

— SPIDER  

Official title:

Specifying the Anti-inflammatory Effects of Ziltivekimab With Diverse Imaging Modalities and In-depth Cellular Phenotyping

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06263244
• Other study ID #: NL83403.018.22
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: April 1, 2024
• Est. completion date: April 1, 2025

Study information

• Verified date: March 2024
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: R.F. Oostveem, MD
• Phone: +312052268791
• Email: r.oostveen[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: April 1, 2025
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atherosclerosis
• Inflammation

Intervention

Drug:
• Ziltivekimab
Monoclonal antibody targeting IL-6
• Placebo
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TBRmax coronary arteries	mean percentage change in coronary arteries target to background ratio (TBRmax)	5.5 months
Primary	monocyte activation marker protein expression	The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16.	5.5 months
Secondary	delta PCAT	Difference in PCAT (CCTA derived) after ziltivekimab treatment.	5.5 months
Secondary	Correlation delta TBRmax and CCTA derived plaque characteristics	Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA.	5.5 months
Secondary	delta SUVmax bone marrow	Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment.	5.5 months
Secondary	delta TBRmax ascending aorta	Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment	5.5 months
Secondary	changes monocyte phenotype	The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile.	5.5 months
Secondary	changes in hsCRP	hsCRP (high-sensitivity C-reactive protein): mg/L	5.5 months
Secondary	changes plasma cytokine and chemokine levels (pg/mL)	TNF-a (Tumor Necrosis Factor alpha): pg/mL IL-8 (Interleukin-8): pg/mL MCP-1 (Monocyte Chemoattractant Protein-1): pg/mL	5.5 months
Secondary	changes plasma cytokine and chemokine levels (ng/mL)	sICAM (soluble Intercellular Adhesion Molecule): ng/mL sVCAM (soluble Vascular Cell Adhesion Molecule): ng/mL	5.5 months