Efficacy of Mepolizumab in Patients With Late-onset Severe Eosinophilic Asthma and Fixed Obstruction

Aristotle University Of Thessaloniki1 个研究点分布在 1 个国家目标入组 45 人开始时间: 2021年1月22日最近更新: 2024年2月21日

适应症

干预措施

试验速览

阶段: 不适用
状态: 进行中（未招募）
发起方: Aristotle University Of Thessaloniki
入组人数: 45
试验地点: 1
主要终点: Identification of clinical characteristics of response, change in FENO levels.

研究概览研究设计入排标准研究组 & 干预措施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

Interleukin (IL)-5 is the main cytokine responsible for the activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in patients with severe asthma.

Response to biologic therapies in severe asthma is variable, with patients being either non-responders, responders or super-responders. There is currently no explanation for this broad variation in response. It is important to examine whether these patients have distinct characteristics that could help the treating physician in making the correct diagnosis in clinical practice.

Aim of this clinical study is to evaluate the efficacy of mepolizumab, a humanized IL-5 antagonist monoclonal antibody in patients with late-onset severe eosinophilic asthma with fixed obstruction and to identify the characteristics of non-responders and super-responders under mepolizumab treatment. This study is considered as non-interventional and every procedure included is happening in a clinical routine for the diagnosis and phenotyping of the asthmatic patients.

Hypothesis includes the efficacy of mepolizumab treatment in late-onset severe eosinophilic asthmatic patients with fixed obstruction and relation to clinical and inflammatory biomarkers.

Patients will be collected from the outpatient clinics of bronchial asthma from each site included (8 in number) which cover the whole population of Greece.

Overall, this is a prospective multicenter study including eight Pulmonary Clinics. Five Pulmonary University Clinics, two of National Health System and one Army General Hospital in Thessaloniki. The study will include a screening period of up to 2 weeks to assess eligibility and obtain written informed consent, a mepolizumab treatment period of 52 weeks, once every 4 weeks, including follow up visits every 3 months during treatment. The study population will consist of 45 patients with late-onset severe eosinophilic asthma and fixed obstruction receiving mepolizumab, aged 20 and above.

详细描述

Scientific rationale Interleukin (IL)-5 is the main cytokine responsible for the activation of eosinophils, hence therapeutic strategies have been investigated and developed for clinical use. Biologics targeting IL-5 and its receptor (first mepolizumab and subsequently, reslizumab and benralizumab), have been recently approved and used as add-on therapy for severe eosinophilic asthma resulting in a reduction in the circulating eosinophil count, improvement in lung function and exacerbation reduction in patients with severe asthma.

Several methods are used to investigate airway inflammation: direct measurements (like bronchial biopsies or bronchoalveolar lavages) and indirect methods (like symptom assessment, blood sample analysis and lung function tests). The direct techniques have the advantage of reliably assessing the airway inflammation, but they are invasive and not feasible at large scale because of patient discomfort and the risk incurred. As for the indirect methods, they poorly correlate with the direct assessment of airway inflammation.

In this study, among patients' clinical characteristics spirometry, biomarkers of inflammation (blood eosinophils, FeNO, IgE levels), impulse oscillometry (IOS) and the thickening of basement membrane via bronchoscopy will be evaluated. It is suggested that late-onset severe eosinophilic asthmatic patients with fixed obstruction who do not respond to the usual treatment (ICS/LABA/LAMA) appear with increased smooth muscle mass. However, the precise effects of increased airway smooth muscle mass on airway narrowing are not known and may vary with disease severity. In addition, biomarkers of inflammation will also be evaluated before and after 52-week mepolizumab treatment in biological fluids (serum, sputum, sputum supernatant and bronchial samples). Biomarkers of inflammation are very important to identify responders to non-responders.

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

入选标准

•Key inclusion criteria
•Written informed consent must be obtained at screening visit, before any assessment will be performed. Subjects should be able to provide informed written consent (study participation informed consent form): Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
•Confirmed asthma diagnosis and severity and treatment requirements.
•Fixed airway obstruction (FAO) where post-bronchodilator treatment ratio of forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] is below < 70%.
•Confirmed optimized management skills (inhaler technique, education, adherence)
•Triggers and relevant co-morbidity have been assessed and managed Triggers such as smoking, beta-blockers, aspirin/NSAIDs, allergen exposure; Comorbidities such as rhinitis, obesity, GERD, OSA, VCD, depression/anxiety.
•Severe asthmatics with blood eosinophils ≥150cells/ul at screening visit or ≥300cells/ul the last 12 months.
•Patients with late-onset severe according to ERS/ATS guidelines eosinophilic asthma and fixed obstruction under the treatment of high dose of ICS+LABA±LAMA (late-onset asthma determined as age at diagnosis from 20 years and above)
•Patients with late-onset severe eosinophilic asthma with history ≥ 1 exacerbation the previous year under the treatment of high dose of ICS+LABA±LAMA.
•Asthma Exacerbation: Subjects with an ongoing asthma exacerbation should have their screening and treatment initiation visit delayed until the investigator considers the subject has returned to their baseline asthma status. If the 4-week screening period has elapsed then the subject should be considered a screening failure. An exacerbation is defined as worsening of asthma requiring the use of systemic corticosteroids and/or emergency department visit, or hospitalization. For subjects on maintenance oral corticosteroids, an exacerbation requiring oral corticosteroids was defined as the use of oral/systemic corticosteroids at least double the existing dose for at least 3 days.
•Maintenance Asthma Therapy: No changes in the dose or regimen of baseline ICS and/or additional controller medication during the screening period (except for treatment of an exacerbation).
•Meet requirements for biologic therapy with mepolizumab.

排除标准

•Asthma exacerbation, within 6 weeks prior to screening that required hospitalization or emergency room visit.
•Prior use of other biologics (including but not limited to Omalizumab, Reslizumab, Dupilumab, Benralizumab etc., for asthma or any other indications) that has potential to interfere/ affect disease progression, in the previous 6 months.
•Pregnant or nursing women, or women of child-bearing potential.
•History of malignancy of any organ system or any other serious co-morbidities defined by the treating physician.
•Patients with a history of conditions other than asthma that could result in elevated eosinophils (e.g. hypereosinophilic syndromes, Churg-Strauss Syndrome, eosinophilic esophagitis).

研究组 & 干预措施

late-onset severe eosinophilic asthma and fixed obstruction

Patients with late-onset severe eosinophilic asthma and fixed obstruction will be administered Mepolizumab (100 MG), subcutaneusly every 30 days

干预措施: Mepolizumab 100 MG [Nucala] (Drug)