Specifying the Anti-inflammatory Effects of Ziltivekimab

NCT06263244 | Recruiting Phase 3

• 1 other identifier: NL83403.018.22
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Atherosclerosis; Inflammation

Keywords

DOTATATE; Ziltivekimab; Inflammation; Monocytes; CCTA; PET/CT

Outcome Measures

Primary Outcomes (2)

• TBRmax coronary arteries

  mean percentage change in coronary arteries target to background ratio (TBRmax)

  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.

  5.5 months

Secondary Outcomes (8)

• delta PCAT

  5.5 months

• Correlation delta TBRmax and CCTA derived plaque characteristics

  5.5 months

• delta SUVmax bone marrow

  5.5 months

• delta TBRmax ascending aorta

  5.5 months

• changes monocyte phenotype

  5.5 months

Study Arms (2)

Ziltivekimab

EXPERIMENTAL

15 mg ziltivekimab subcutaneously once per month for 5 months

Drug: Ziltivekimab

Placebo

PLACEBO COMPARATOR

Placebo, subcutaneously, once per month for 5 months

Drug: Placebo

Interventions

Ziltivekimab DRUG

Monoclonal antibody targeting IL-6

Also known as: no other intervention name

Ziltivekimab

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 50 years and older.
• Multi-vessel coronary artery disease (defined as CAD-RADS ≥2).
• Serum hsCRP level ≥2 mg/L.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Amsterdam UMC, location AMC

Amsterdam, 1105AZ, Netherlands

RECRUITING

MeSH Terms

Conditions

Atherosclerosis; Inflammation

Interventions

ziltivekimab

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• E.S.G. Stroes, Prof.dr.

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cheyenne Y.Y. Beverloo, MD

CONTACT

+31205669111; c.y.beverloo@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: After informed consent has been obtained, patients will be randomized via computer randomization to either 15 mg ziltivekimab (n=20) or placebo (n=20). On the eCRFs or other documents subjects will be identified by subject ID and randomization number only.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. E.S.G. Stroes

Model Details: randomized, double blind, placebo-controlled trial

Study Record Dates

• First Submitted: August 3, 2023
• First Posted: February 16, 2024
• Study Start: May 3, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: October 2, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)