Blood Leukocyte Profiling in Eosinophilic Type 2 Asthma: Influence of Systemic IL-5 Targeting
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- Region Skane
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change in Blood Eosinophil Marker Expression
研究概览
简要总结
The goal of this exploratory and observational prospective study is to study the composition and phenotypes of blood leukocytes collected from asthmatic patients before and after instantiated treatment with the interleukin-5 neutralizing antibody mepolizumab. Comparisons will be made to leukocyte profiles in patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.
详细描述
Asthma is a chronic inflammatory and obstructive condition affecting the airways. The disease is commonly associated with elevated blood eosinophils and tissue eosinophilia. Many aspects of the pathophysiological mechanisms and clinical symptoms are controlled by conventional therapies such as inhaled corticosteroids (ICS) and long acting β2 agonists. However, some patients remain clinically uncontrolled and need additional treatment such as direct targeting of eosinophil granulocytes by neutralizing the eosinophil-promoting cytokine interleukin 5 (IL5). Mepolizumab is a humanized monoclonal IL-5 neutralizing antibody that is used to treat patients with moderate-severe eosinophilic asthma. While a marked reduction of eosinophils is a key effect of mepolizumab, the exact mechanism of action is unknown. Apart from basophils, that also express the receptor for IL-5, other leukocytes are likely to be indirectly affected by the suppressed eosinophilia. In addition, it is largely unknown to what extent the few eosinophils remaining after anti-IL5 treatment differ from pre-treatment eosinophils.
The present study is a prospective observational asthma study that aims to use microscopic analysis to investigate the composition and subtypes of blood leukocytes collected before and after instantiated mepolizumab treatment. Comparisons are made to patients already on mepolizumab treatment, asthma patients without any biological treatment, and non-diseased control subjects.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Clinical diagnosis of asthma (the asthma patient arms)
- •Eligible for Mepolizumab treatment as per the country-specific prescribing information (the arms with Mepolizumab)
- •Exclusion criteria:
- •Any diagnosed infection (all arms)
- •Previous history of lung disease, chronic inflammatory condition, atopy, or cardiovascular disease. Diagnosed or perceived infection within 3 weeks prior to blood sampling (Healthy non-asthma control subjects)
排除标准
- 未提供
研究组 & 干预措施
Asthma patients initiating Mepolizumab treatment
Patients will be selected on the standard criteria used to select eligible asthma patients for mepolizumab treatment (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients may be included. Exclusion criteria: any infection
干预措施: Mepolizumab (Biological)
Asthma patients initiating Mepolizumab treatment
Patients will be selected on the standard criteria used to select eligible asthma patients for mepolizumab treatment (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients may be included. Exclusion criteria: any infection
干预措施: Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA) (Drug)
Asthma patients already on Mepolizumab treatment
Patients that have been selected and given Mepolizumab treatment for > 4 months according to standard eligible and treatment regimen criteria (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients that have been on Mepolizumab treatment for > 4 weeks will be included. Exclusion criteria: any infections
干预措施: Mepolizumab (Biological)
Asthma patients already on Mepolizumab treatment
Patients that have been selected and given Mepolizumab treatment for > 4 months according to standard eligible and treatment regimen criteria (i.e. patients with eosinophilic asthma that are not controlled by conventional high dose ICS and LABA etc). All eligible asthma patients that have been on Mepolizumab treatment for > 4 weeks will be included. Exclusion criteria: any infections
干预措施: Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA) (Drug)
Asthma patients without Mepolizumab treatment
Inclusion: Asthma patients without any biological (antibody-based) treatment but on routine ICS and LABA treatment as part of their normal care. Exclusion criteria are any infections
干预措施: Standard inhaled corticosteroids (ICS) and long-acting beta 2 agonists (LABA) (Drug)
结局指标
主要结局
Change in Blood Eosinophil Marker Expression
时间窗: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Quantitative immunohistochemical analysis of eosinophil marker expression in blood leukocyte pellets
Change in Blood Basophil Marker Expression
时间窗: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Quantitative immunohistochemical analysis of basophil marker expression in blood leukocyte pellets
Change in Blood Leukocyte Composition
时间窗: Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment
Immunohistochemical determination of the relative proportion (percent) of the leukocyte populations in blood leukocyte pellets
次要结局
- Change in Blood T Lymphocyte Marker Expression(Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment)
- Change in Blood B Lymphocyte Marker Expression(Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment)
- Leukocyte Total Cell Counts(Change from baseline at 1-3 days, 1 week, 4 weeks, and 4 months after initiated biological treatment)