Specifying the Anti-inflammatory Effects of Ziltivekimab (SPIDER)

September 30, 2025 updated by: E.S.stroes, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1105AZ
        • Recruiting
        • Amsterdam UMC, location AMC

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Ziltivekimab
15 mg ziltivekimab subcutaneously once per month for 5 months
Drug: Ziltivekimab
Monoclonal antibody targeting IL-6
Other Names:
  • no other intervention name
Placebo Comparator: Placebo
Placebo, subcutaneously, once per month for 5 months
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
TBRmax coronary arteries
Time Frame: 5.5 months
mean percentage change in coronary arteries target to background ratio (TBRmax)
5.5 months
monocyte activation marker protein expression
Time Frame: 5.5 months
The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16.
5.5 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
delta PCAT
Time Frame: 5.5 months
Difference in PCAT (CCTA derived) after ziltivekimab treatment.
5.5 months
Correlation delta TBRmax and CCTA derived plaque characteristics
Time Frame: 5.5 months
Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA.
5.5 months
delta SUVmax bone marrow
Time Frame: 5.5 months
Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment.
5.5 months
delta TBRmax ascending aorta
Time Frame: 5.5 months
Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment
5.5 months
changes monocyte phenotype
Time Frame: 5.5 months
The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile.
5.5 months
changes in hsCRP
Time Frame: 5.5 months
hsCRP (high-sensitivity C-reactive protein): mg/L
5.5 months
changes plasma cytokine and chemokine levels (pg/mL)
Time Frame: 5.5 months
TNF-α (Tumor Necrosis Factor alpha): pg/mL IL-8 (Interleukin-8): pg/mL MCP-1 (Monocyte Chemoattractant Protein-1): pg/mL
5.5 months
changes plasma cytokine and chemokine levels (ng/mL)
Time Frame: 5.5 months
sICAM (soluble Intercellular Adhesion Molecule): ng/mL sVCAM (soluble Vascular Cell Adhesion Molecule): ng/mL
5.5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: E.S.G. Stroes, Prof.dr., Amsterdam UMC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 3, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 3, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 8, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 16, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 2, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL83403.018.22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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