Spécifier les effets anti-inflammatoires du Ziltivekimab (SPIDER)
Spécifier les effets anti-inflammatoires du ziltivekimab avec diverses modalités d'imagerie et un phénotypage cellulaire approfondi
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.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
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.
Type d'étude
Inscription (Réel)
Phase
- Phase 3
Contacts et emplacements
Lieux d'étude
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-
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Amsterdam, Pays-Bas, 1105AZ
- Amsterdam UMC, location AMC
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La 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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: La prévention
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Quadruple
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Ziltivekimab
15 mg ziltivekimab subcutaneously once per month for 5 months |
Monoclonal antibody targeting IL-6
Autres noms:
|
|
Comparateur placebo: Placebo
Placebo, subcutaneously, once per month for 5 months |
Placebo |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
TBRmax coronary arteries
Délai: 5.5 months
|
mean percentage change in coronary arteries target to background ratio (TBRmax) |
5.5 months
|
|
monocyte activation marker protein expression
Délai: 5.5 months
|
The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16. |
5.5 months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
delta PCAT
Délai: 5.5 months
|
Difference in PCAT (CCTA derived) after ziltivekimab treatment. |
5.5 months
|
|
Correlation delta TBRmax and CCTA derived plaque characteristics
Délai: 5.5 months
|
Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA. |
5.5 months
|
|
delta SUVmax bone marrow
Délai: 5.5 months
|
Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment. |
5.5 months
|
|
delta TBRmax ascending aorta
Délai: 5.5 months
|
Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment |
5.5 months
|
|
changes monocyte phenotype
Délai: 5.5 months
|
The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile. |
5.5 months
|
|
changes in hsCRP
Délai: 5.5 months
|
hsCRP (high-sensitivity C-reactive protein): mg/L |
5.5 months
|
|
changes plasma cytokine and chemokine levels (pg/mL)
Délai: 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)
Délai: 5.5 months
|
sICAM (soluble Intercellular Adhesion Molecule): ng/mL sVCAM (soluble Vascular Cell Adhesion Molecule): ng/mL |
5.5 months
|
Collaborateurs et enquêteurs
Les enquêteurs
- Chercheur principal: E.S.G. Stroes, Prof.dr., Amsterdam UMC
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- NL83403.018.22
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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