Pharmaco Kinetic and Pharmacokinetic-Pharmacodynamic Variability of Infliximab
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 84
- 试验地点
- 6
- 主要终点
- Characterizing the PK and PK-PD variability of infliximab in RA
研究概览
简要总结
Infliximab is a chimeric monoclonal antibody directed towards Tumor Necrosis Factor -alpha that is largely used in inflammatory diseases such as rheumatoid arthritis (RA).
A relationship between dose and clinical outcomes was shown in populations of RA patients but there is an interindividual variability of this relationship. At an individual level, this dose-effet relationship can be separated into the dose-concentration (pharmacokinetic or PK) and the concentration-effet (pharmacokinetic-pharmacodynamic or PK-PD) relationships.
Serum trough concentrations of infliximab have been shown to be variable between patients receiving the same treatment regimen. This PK variability may be explained by several factors (e.g. genetic and immunological factors). The concentration-effect relationship may also be variable and the sources of this variability need to be studied as well. To date no detailed infliximab PK analysis has been published. The sources of variability of the dose-effect relationship need to be characterized to optimize infliximab dosing regimen in patients.
The FAKIR study is a multicenter prospective observational study that will focus on patients treated with infliximab. Its aims are:
- to characterize the PK and PK-PD variability of infliximab in RA, using clinical criteria and biomarkers, assessed over time ;
- to study the influence of the polymorphism of FCGRT (the gene encoding FcRn) on the PK variability of infliximab; to study the influence of the polymorphism of FCGR3A (the gene encoding Fc gamma RIIIa) on the PK-PD variability of infliximab; and to study the influence of antibodies toward infliximab on the PK and PK-PD variabilities of infliximab.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Rheumatoid arthritis according to ACR criteria
- •Patient already receiving infliximab for more than 14 weeks
- •No modification of the dose regimen of infliximab since the last infusion
- •No modification of disease modifying anti rheumatic drugs since the last 4 weeks
排除标准
- •Surgery scheduled during the duration of the study
- •Pregnancy
- •infection, malignancy, immune reaction to infliximab or demyelinating diseases
结局指标
主要结局
Characterizing the PK and PK-PD variability of infliximab in RA
时间窗: 6 to 12 weeks
次要结局
- Studying the relation between FCGRT polymorphism and the PK variability of infliximab; the relation between FCGR3A polymorphism and the PK-PD variability of infliximab; and the relation between ATI and the PK and PK-PD variabilities of infliximab(6 to 12 weeks)