NCT06288516招募中4 期

BenRalizumab Effect on Airway Remodeling in Severe Eosinophilic asTHmatics

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: 2024年3月1日最近更新: 2024年3月4日

研究概览

简要总结

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 benralizumab, a humanized an anti-interleukin 5 receptor α monoclonal antibody in patients with severe eosinophilic asthma and to evaluate airway remodeling before and after benralizumab treatment.

Hypothesis Identification of pathological and clinical characteristics in patients with severe eosinophilic asthma after benralizumab treatment regarding the airway remodeling, inflammatory cells, and other biomarkers on a long-term basis.

Research questions Is there any improvement in airway remodeling? Are there any biomarkers to predict response to benralizumab treatment in severe eosinophilic asthmatic patients?

详细描述

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 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 benralizumab, a humanized an anti-interleukin 5 receptor α monoclonal antibody in patients with severe eosinophilic asthma and to evaluate airway remodeling before and after benralizumab treatment. Every patient will be a control to himself by comparing baseline's biomarker measurements of each patient to the following timepoint's measurements. However, we have added 10 severe asthmatics with no intervention, receiving standard of care as control groups to make more comparisons.

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 such as blood eosinophils, Fractional Exhaled Nitric Oxide (FeNO), immunoglobulin E (IgE) levels), and airway remodeling via bronchoscopy will be evaluated. The precise effects of increased airway smooth muscle area 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 of benralizumab treatment in biological fluids (serum and bronchial samples). Biomarkers of inflammation are very important to identify treatment response.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 85 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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 severe asthma diagnosis and treatment requirements according to American Thoracic Society(ATS)/European Respiratory Society (ERS) guidelines and Global Initiative for Asthma (GINA)
•Blood eosinophils ≥150cells/ul at screening visit or ≥300cells/ul the last 12 months.
•Patients with history ≥ 1 exacerbation the previous year under the treatment of high dose of inhaled corticosteroid(ICS)+LABA±LAMA or receiving oral/systemic corticosteroids at least 3 days. 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.
•Meet requirements for biologic therapy with Benralizumab.

排除标准

•Asthma exacerbation, within 6 weeks prior to screening that required hospitalization or emergency room visit.
•Prior use of other biologics that has potential to interfere/ affect disease progression.
•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

Benralizumab Arm A

Experimental

Benralizumab (30mg) administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks.

干预措施: Benralizumab 30 mg/ml (Drug)