Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Change in Platelet Count From Baseline to Follow-up
研究概览
简要总结
The purpose of this study is to evaluate the effects of IL-1β inhibition on safety, measures of systemic and vascular inflammation and endothelial function (all indicators of cardiovascular risk) in treated and suppressed HIV infected individuals This study will assess the safety and effects of canakinumab on endothelial function (assessed by flow-mediated vasodilation [FMD] of the brachial artery), vascular inflammation (assessed by FDG-PET/CT scanning), key inflammatory markers of cardiovascular disease (CVD) risk (high-sensitivity C-reactive protein [hsCRP]), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir. 10 individuals will receive a single dose of 150mg canakinumab with follow-up for 12 weeks. In the second part of the study, 100 participants will be randomized (2:1 - canakinumab to placebo) and will be followed by for 36 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 59 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV infection,
- •Age ≥ 40 years < 60 years
- •On continuous ART for at least 12 months with no change in regimen in 12 weeks prior to study entry
- •CD4+ T cell count ≥ 400 cells/mm3
- •HIV RNA level below the standard limit of quantification for 52 weeks prior to entry
- •High risk for CAD as defined by either documented CVD (including prior MI) or diabetes mellitus or 1 CVD risk factor (current smoking, hypertension, dyslipidemia, or hsCRP≥2mg/L.)
- •Individuals on stable doses of lipid lowering therapy and/or anti-hypertensive medication will be allowed in the study.
- •Appropriate documentation from medical records of prior receipt of pneumococcal vaccinations
排除标准
- •Women of childbearing potential or pregnant/nursing women
- •CABG surgery in the past 3 years
- •Class IV heart failure
- •Uncontrolled HTN
- •History of tuberculosis or latent TB that is not treated
- •Nephrotic syndrome or eGFR< 30 ml/min/1.73m2
- •Active hepatic disease or active/chronic hepatitis B or C
- •Any prior malignancy including KS
- •Serious illness requiring hospitalization or active infection requiring antibiotics within 90 days
- •Requirement for live active vaccination 3 months prior to, during, and 3 months after study
- •Concurrent immune modulating therapy
- •Diabetes Mellitus
- •History of multiple imaging studies associated with radiation exposure
- •Neutropenia defined as ANC<1500/mm
- •Triglycerides>400 mg/dL
- •History of hypersensitivity to study drug
- •History of EBV-related lymphoproliferative disorders
- •Active or untreated latent TB infection
研究组 & 干预措施
Safety Arm
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
干预措施: Canakinumab (Drug)
Canakinumab
In Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection.
干预措施: Canakinumab (Drug)
Placebo
In Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Platelet Count From Baseline to Follow-up
时间窗: weeks 4, 8, 12, 18, 24, and 36.
Change in platelet count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Change in Creatinine Count From Baseline to Follow-up
时间窗: weeks 4, 8, 12, 18, 24, and 36.
Change in creatinine count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Change in CD4 Count From Baseline to Follow-up
时间窗: weeks 4, 8, 12, 18, 24, and 36.
Change in CD4 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Change in ALT From Baseline to Follow-up
时间窗: weeks 4, 8, 12, 18, 24, and 36.
Change in ALT from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Change in CD8 Count From Baseline to Follow-up
时间窗: weeks 4, 8, 12, 18, 24, and 36.
Change in CD8 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Change in Absolute Neutrophil Count From Baseline to Follow-up
时间窗: weeks 4, 8, 12, 18, 24, and 36.
Change in absolute neutrophil count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Change in AST From Baseline to Follow-up
时间窗: weeks 4, 8, 12, 18, 24, and 36.
Change in AST from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
次要结局
- D-Dimer(Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18)
- Tumor Necrosis Factor Alpha (TNFa)(Baseline, 4 weeks, 12 weeks, and week 18)
- Arterial Inflammation Measured at Baseline and Follow-up at Week 12(Baseline (entry) and Week 12)
- Human Serum Amyloid A (SAA)(Baseline, 4 weeks, 12 weeks, and week 18)
- Flow-Mediated Dilation (FMD)(Baseline and Week 12)
研究者
Priscilla Hsue, MD
Professor of Medicine
University of California, San Francisco