明确 Ziltivekimab 的抗炎作用 (SPIDER)
通过多种成像方式和深入的细胞表型分析确定 Ziltivekimab 的抗炎作用
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.
研究概览
详细说明
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.
研究类型
注册 (实际的)
阶段
- 第三阶段
联系人和位置
学习地点
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Amsterdam、荷兰、1105AZ
- Amsterdam UMC, location AMC
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Ziltivekimab
15 mg ziltivekimab subcutaneously once per month for 5 months |
Monoclonal antibody targeting IL-6
其他名称：
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安慰剂比较：Placebo
Placebo, subcutaneously, once per month for 5 months |
Placebo |
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
TBRmax coronary arteries
大体时间：5.5 months
|
mean percentage change in coronary arteries target to background ratio (TBRmax) |
5.5 months
|
|
monocyte activation marker protein expression
大体时间：5.5 months
|
The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16. |
5.5 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
delta PCAT
大体时间：5.5 months
|
Difference in PCAT (CCTA derived) after ziltivekimab treatment. |
5.5 months
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Correlation delta TBRmax and CCTA derived plaque characteristics
大体时间：5.5 months
|
Correlation between changes in coronary 68Ga-DOTATATE uptake and anatomical plaque changes on CCTA. |
5.5 months
|
|
delta SUVmax bone marrow
大体时间：5.5 months
|
Difference in 68Ga-DOTATATE SUVmax of bone marrow after treatment. |
5.5 months
|
|
delta TBRmax ascending aorta
大体时间：5.5 months
|
Difference in 68Ga-DOTATATE TBRmax of ascending aorta after treatment |
5.5 months
|
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changes monocyte phenotype
大体时间：5.5 months
|
The impact of ziltivekimab on monocyte phenotype in transendothelial migration (TEM) capacity and transcriptome profile. |
5.5 months
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|
changes in hsCRP
大体时间：5.5 months
|
hsCRP (high-sensitivity C-reactive protein): mg/L |
5.5 months
|
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changes plasma cytokine and chemokine levels (pg/mL)
大体时间：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
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changes plasma cytokine and chemokine levels (ng/mL)
大体时间：5.5 months
|
sICAM (soluble Intercellular Adhesion Molecule): ng/mL sVCAM (soluble Vascular Cell Adhesion Molecule): ng/mL |
5.5 months
|
合作者和调查者
调查人员
- 首席研究员：E.S.G. Stroes, Prof.dr.、Amsterdam UMC
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- NL83403.018.22
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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