Exacerbation Profile in Patients on Mepolizumab for Severe Refractory Eosinophilic Asthma- an Exploratory Study.

Queen's University, Belfast4 个研究点分布在 1 个国家目标入组 146 人开始时间: 2017年12月1日最近更新: 2019年7月10日

适应症

试验速览

阶段: 不适用
状态: 已完成
发起方: Queen's University, Belfast
入组人数: 146
试验地点: 4
主要终点: Asthma control questionnaire (ACQ)

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a multicentre, observational study focusing on exacerbation events in patients with severe eosinophilic asthma on Mepolizumab.

Mepolizumab is an anti-IL5 (Interleukin 5) monoclonal antibody which blocks the eosinophilic activation pathways associated with decreasing asthma control. The pre-licensing studies have shown that Mepolizumab decreases asthma exacerbation events by approximately 50%, this study seeks to understand the underlying mechanisms of the remaining 50% of exacerbations.

The study will enrol patients within GINA classification 4 and 5 who are known to difficult asthma services across four UK sites. Some patients will recently have been commenced on Mepolizumab, whilst others will be commenced on the drug on entry to the study. The patients will have baseline measurements of biomarkers, lung function, sputum analysis and quality of life questionnaires on study entry, after which patients will be asked to contact the clinic at the first signs of worsening asthma symptoms to arrange a clinic visit prior to commencing rescue treatment. They will be clinically assessed with review of peak flow and symptom diaries, measurements taken at baseline will be repeated and a decision on the nature of the exacerbation and treatment required will be made.

This is an observational study, all outcomes will be exploratory.

详细描述

Background:

Around 15% of the United Kingdom (UK) have asthma, of these, 10-20% have asthma which is difficult to control using current therapies and with high levels of morbidity resulting. These patients consume 50-60% of the UK healthcare costs of asthma and as such, there is much interest in developing novel treatments for this group.

The heterogeneity of inflammatory pathways underlying asthma are of great interest with development of biomarkers useful for phenotyping asthmatic patients and allowing more accurate assessment of their response to treatment. Traditionally, oral corticosteroids are used in eosinophilic 'T2-high' asthmatic patients with good therapeutic effect, however, there are a group of T2-high patients who have refractory type-2 cytokine driven inflammation and airway eosinophilia despite oral corticosteroids. As such, there are several novel biological agents being engineered to block type 2 cytokine pathways including antagonists to IL5, IL13 and IL4 (Interleukin 5, 13, 4).

Mepolizumab is a humanised monoclonal antibody against IL5. Through a selective inhibition of eosinophilic inflammation, the agent reduces the number of eosinophils in sputum and blood, with important clinical outcomes such as a reduction of asthma exacerbations and a need for systemic glucocorticoids. The pre-licencing clinical trials have shown that selective inhibition of IL5 and presumptive removal of eosinophils reduces exacerbations by 50%, but while this is a significant reduction, patients with severe asthma continue to have severe exacerbations requiring systemic corticosteroid administration.

Therefore, the point of interest is eliciting the inflammatory phenotype and physiological characteristics of the remaining 50% of exacerbations and ascertaining whether systemic corticosteroids have a role when the IL-5 pathway has been blocked by Mepolizumab.

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 80 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Age ≥ 18 and ≤ 80 years at Visit 1
•Able and willing to provide written informed consent and to comply with the study protocol including being able to contact the clinical center and to attend for assessment during a symptomatic deterioration
•Severe asthma despite confirmed after assessment by an asthma specialist
•Diagnosed with asthma at least 12 months prior to screening

排除标准

•Acute exacerbation requiring oral corticosteroids in 4 weeks before screening.
•Other clinically significant medical disease or uncontrolled concomitant disease despite treatment that is likely, in the opinion of the investigator, to require a change in therapy or impact the ability to participate in the study
•History of current alcohol, drug, or chemical abuse or past abuse that would impair or risk the subject's full participation in the study, in the opinion of the investigator
•Treatment with an investigational agent within 30 days of visit 1 (or 5 half-lives of the investigational agent, whichever is longer)
•Female subjects who are pregnant or lactating (excluded as candidates for Mepolizumab in clinic prior to study)