Specifying the Anti-inflammatory Effects of Ziltivekimab With Diverse Imaging Modalities and In-depth Cellular Phenotyping
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- TBRmax coronary arteries
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
After informed consent has been obtained, patients will be randomized via computer randomization to either 15 mg ziltivekimab (n=20) or placebo (n=20). On the eCRFs or other documents subjects will be identified by subject ID and randomization number only.
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 50 years and older.
- •Multi-vessel coronary artery disease (defined as CAD-RADS ≥2).
- •Serum hsCRP level ≥2 mg/L.
排除标准
- •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 m
- •Platelet count <120,000 and >450,000 /mm
- •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.
研究组 & 干预措施
Placebo
Placebo, subcutaneously, once per month for 5 months
干预措施: Placebo (Drug)
Ziltivekimab
15 mg ziltivekimab subcutaneously once per month for 5 months
干预措施: Ziltivekimab (Drug)
结局指标
主要结局
TBRmax coronary arteries
时间窗: 5.5 months
mean percentage change in coronary arteries target to background ratio (TBRmax)
monocyte activation marker protein expression
时间窗: 5.5 months
The impact of ziltivekimab on a mass cytometry monocyte phenotype panel; expression markers such as CD14 and CD16.
次要结局
- delta PCAT(5.5 months)
- delta TBRmax ascending aorta(5.5 months)
- changes in hsCRP(5.5 months)
- changes plasma cytokine and chemokine levels (pg/mL)(5.5 months)
- delta SUVmax bone marrow(5.5 months)
- changes monocyte phenotype(5.5 months)
- Correlation delta TBRmax and CCTA derived plaque characteristics(5.5 months)
- changes plasma cytokine and chemokine levels (ng/mL)(5.5 months)
研究者
E.S.stroes
Prof. dr. E.S.G. Stroes
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)