Specificering av de antiinflammatoriska effekterna av Ziltivekimab (SPIDER)
Specificering av de antiinflammatoriska effekterna av Ziltivekimab med olika avbildningsmodaliteter och djupgående cellulär fenotypning
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.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 3
Kontakter och platser
Studieorter
-
-
-
Amsterdam, Nederländerna, 1105AZ
- Amsterdam UMC, location AMC
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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.
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Förebyggande
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Fyrdubbla
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: Ziltivekimab
15 mg ziltivekimab subcutaneously once per month for 5 months |
Monoclonal antibody targeting IL-6
Andra namn:
|
|
Placebo-jämförare: Placebo
Placebo, subcutaneously, once per month for 5 months |
Placebo |
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
TBRmax coronary arteries
Tidsram: 5.5 months
|
mean percentage change in coronary arteries target to background ratio (TBRmax) |
5.5 months
|
|
monocyte activation marker protein expression
Tidsram: 5.5 months
|
The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16. |
5.5 months
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
delta PCAT
Tidsram: 5.5 months
|
Difference in PCAT (CCTA derived) after ziltivekimab treatment. |
5.5 months
|
|
Correlation delta TBRmax and CCTA derived plaque characteristics
Tidsram: 5.5 months
|
Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA. |
5.5 months
|
|
delta SUVmax bone marrow
Tidsram: 5.5 months
|
Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment. |
5.5 months
|
|
delta TBRmax ascending aorta
Tidsram: 5.5 months
|
Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment |
5.5 months
|
|
changes monocyte phenotype
Tidsram: 5.5 months
|
The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile. |
5.5 months
|
|
changes in hsCRP
Tidsram: 5.5 months
|
hsCRP (high-sensitivity C-reactive protein): mg/L |
5.5 months
|
|
changes plasma cytokine and chemokine levels (pg/mL)
Tidsram: 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)
Tidsram: 5.5 months
|
sICAM (soluble Intercellular Adhesion Molecule): ng/mL sVCAM (soluble Vascular Cell Adhesion Molecule): ng/mL |
5.5 months
|
Samarbetspartners och utredare
Utredare
- Huvudutredare: E.S.G. Stroes, Prof.dr., Amsterdam UMC
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Faktisk)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- NL83403.018.22
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Studerar en amerikansk FDA-reglerad produktprodukt
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .