AtherosclerosisPhase 3SPIDERNCT06263244
Specifying the Anti-inflammatory Effects of Ziltivekimab
A Phase 3 study testing Ziltivekimab in people with Atherosclerosis and Inflammation, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Atherosclerosis, Inflammation
- What is being tested?
- Ziltivekimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteNetherlands
- Study dates
- 3 May 2024to 30 Oct 2026
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 50 years and older.
- Multi-vessel coronary artery disease (defined as CAD-RADS ≥2).
- Serum hsCRP level ≥2 mg/L.
Who cannot join
- 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
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Atherosclerosis, Inflammation
- Being tested
- Ziltivekimab, Placebo
- Keywords
- DOTATATE, Ziltivekimab, Inflammation, Monocytes, CCTA, PET/CT
- Medical subject headings
- Atherosclerosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZiltivekimabDrug
Also called no other intervention name
Monoclonal antibody targeting IL-6
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Ziltivekimab | Experimental | 15 mg ziltivekimab subcutaneously once per month for 5 months Receives: Drug: Ziltivekimab |
| Placebo | Placebo comparator | Placebo, subcutaneously, once per month for 5 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
TBRmax coronary arteries
mean percentage change in coronary arteries target to background ratio (TBRmax)
Measured: 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.
Measured: 5.5 months
Secondary outcomes (8)
delta PCAT
Difference in PCAT (CCTA derived) after ziltivekimab treatment.
Measured: 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.
Measured: 5.5 months
delta SUVmax bone marrow
Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment.
Measured: 5.5 months
delta TBRmax ascending aorta
Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment
Measured: 5.5 months
changes monocyte phenotype
The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile.
Measured: 5.5 months
changes in hsCRP
hsCRP (high-sensitivity C-reactive protein): mg/L
Measured: 5.5 months
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
Measured: 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
Measured: 5.5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2024
- Study start3 May 2024
- Primary completion30 Oct 2026
- Study completion30 Oct 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, double blind, placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, E.S.stroes, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- E.S.G. Stroes, Prof.dr., Principal investigator, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06263244
- Sponsor's protocol ID
- NL83403.018.22
- Acronym
- SPIDER
- Status last verified
- Nov 2026
- First submitted
- 3 Aug 2023
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Specifying the Anti-inflammatory Effects of Ziltivekimab With Diverse Imaging Modalities and In-depth Cellular Phenotyping
- ClinicalTrials.gov ID
- NCT06263244
- Acronym / sponsor ID
- SPIDER / NL83403.018.22
- Conditions
- Atherosclerosis, Inflammation
- Keywords
- DOTATATE, Ziltivekimab, Inflammation, Monocytes, CCTA, PET/CT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- 3 May 2024 (actual)
- Primary completion
- 30 Oct 2026 (actual)
- Study completion
- 30 Oct 2026 (actual)
- First posted
- 16 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- randomized, double blind, placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Ziltivekimab | Experimental | Drug: Ziltivekimab15 mg ziltivekimab subcutaneously once per month for 5 months |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo, subcutaneously, once per month for 5 months |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Aged 50 years and older.
- Multi-vessel coronary artery disease (defined as CAD-RADS ≥2).
- Serum hsCRP level ≥2 mg/L.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZiltivekimabAlso: no other intervention nameMonoclonal antibody targeting IL-6 | Drug | Ziltivekimab |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
TBRmax coronary arteries
Time frame: 5.5 months
mean percentage change in coronary arteries target to background ratio (TBRmax)
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.
8 secondary outcomes
delta PCAT
Time frame: 5.5 months
Correlation delta TBRmax and CCTA derived plaque characteristics
Time frame: 5.5 months
delta SUVmax bone marrow
Time frame: 5.5 months
delta TBRmax ascending aorta
Time frame: 5.5 months
changes monocyte phenotype
Time frame: 5.5 months
changes in hsCRP
Time frame: 5.5 months
changes plasma cytokine and chemokine levels (pg/mL)
Time frame: 5.5 months
changes plasma cytokine and chemokine levels (ng/mL)
Time frame: 5.5 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
E.S.G. Stroes, Prof.dr. principal investigator
Amsterdam UMC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ziltivekimab in people with Atherosclerosis and Inflammation, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TBRmax coronary arteries (time frame: 5.5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.