2024-514843-27-00招募中4 期
Predictive Signature of Benralizumab Response. BENRAPRED Study.
Centre Hospitalier Universitaire De Nantes14 个研究点 分布在 1 个国家目标入组 220 人开始时间: 2024年6月24日最近更新:
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 220
- 试验地点
- 14
- 主要终点
- We will evaluate an early blood gene expression signature of Benralizumab response through a clinically relevant reduction of the number of exacerbations at M12 assessed in: - Three patient response groups (responders, intermediates responders, non-responders), - Gene expression signature. A 3 categories Pi-PLS-DA analysis will identify the major molecular discriminants of the responders groups.
研究概览
简要总结
To establish the predictive value of early blood gene expression signature of Benralizumab response associated with a significant reduction of the number of exacerbations in treated severe asthmatic patients.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Patients between 18 and 75 years old
- •Patients diagnosed with severe asthma (Chung and al, Eur Respir J 2014), i.e.: asthma requiring high doses of ICS (>1000 microgram per day of Beclomethasone or equivalent) associated with LABA and/or systemic corticosteroids to be controlled over one year, and/or uncontrolled asthma despite the later medications, and/or a controlled asthma worsening after decreasing medications
- •Documented historical reversibility of FEV1 ≥12% and FEV1 gain ≥ 200mL
- •ACQ-7 score ≥ 1,5 at M0
- •At least 3 exacerbations in the 12 months prior to inclusion visit M0
- •Eosinophil blood count ≥ 0,3 G/L at inclusion visit or in the 12 months prior to the inclusion visit. If eosinophil blood count is ≥ 0,15 G/L and < 0,3 G/L, an eosinophilic phenotype defined by at least 1 of the following criteria will be required: FeNO > 25 ppm at inclusion visit or in the 12 months prior to the inclusion visit, or/and Sputum eosinophils at leat 3% at inclusion visit or in the 12 months prior to the inclusion visit
- •Patient who has never received treatment with Benralizumab before prior to participation in the study
- •Patients who provide written informed consent prior to participation in the study
排除标准
- •Patients diagnosed with difficult-to-treat asthma and/or with uncontrolled asthma differential diagnosis according to the judgment of the investigator (e.g., vocal cord dysfunction, gastroesophageal reflux disease, granulomatous eosinophilic vasculitis, obstructive sleep apnea syndrome, hyperventilation syndrome, allergic broncho-pulmonary aspergillosis, Carrington disease, DIPNECH, asthma/COPD overlap syndrome).
- •Patients requiring other biotherapy than Benralizumab that affects the immune system
- •SARS-COV2 infection
- •Pregnancy, lactation, or patients with childbearing potential refusing efficient contraceptive method.
- •Patients under psychiatric condition altering their comprehension and their ability to give informed consent.
- •Patients already enrolled in a clinical interventional research.
- •Patients not affiliated to a health insurance plan
- •Patients under guardianship, curatorship or safeguard of justice
- •Non-adherent patients to inhaled treatment (ICS + LABA).
- •Active smokers or former smokers exceeding 20 packs year.
- •Exacerbation at inclusion visit M0
- •Active malignancy or malignancy in remission over less than 5 years.
- •Active parasitic infection or parasitic infection in the past 24 weeks.
- •Hypersensitivity to Benralizumab or to any of the excipients of Fasenra® (histidine, histidine hydrochloride monohydrate, trehalose dihydrate, polysorbate 20)
- •Patients requiring other immunosuppressive and immunomodulator drugs
- •Patients requiring other biotherapy than Benralizumab, with or without French’s marketing authorisation in severe asthma
结局指标
主要结局
We will evaluate an early blood gene expression signature of Benralizumab response through a clinically relevant reduction of the number of exacerbations at M12 assessed in: - Three patient response groups (responders, intermediates responders, non-responders), - Gene expression signature. A 3 categories Pi-PLS-DA analysis will identify the major molecular discriminants of the responders groups.
We will evaluate an early blood gene expression signature of Benralizumab response through a clinically relevant reduction of the number of exacerbations at M12 assessed in: - Three patient response groups (responders, intermediates responders, non-responders), - Gene expression signature. A 3 categories Pi-PLS-DA analysis will identify the major molecular discriminants of the responders groups.
次要结局
- At M0 a composite blood molecular signature predictive of reduction of the exacerbation rate at M12 in severe asthmatic patients treated by Benralizumab will be assessed as mentioned above. The definition of stable class of patients (low category) is used as a target for the prediction. Methods used for the primary objective (PO) applies to SO1 using similar input data on a different 3-class prediction target.
- The significance of center and the relevance of time dependent modelling will be evaluated using Generalised Mixed Models on independently established molecular response signature. It is expected a robust and reproducible gene expression to assess the inter and intra-individual trajectories of the signature over time and across centers (from early at M0 and M3, to late prediction at M6 and M9).
- Correlations network between blood gene expression of Benralizumab significant response will be assessed thanks to weighted gene correlation network analysis (gene co-expression network analysis (WGCNA)) with an expected increase in FEV1 + AQLQ + peak-flow values and expected decrease of ACQ-7, ACQ-6 scores
- Correlations network between blood gene expression at M0 and clinical characteristics of frequent exacerbations will be assessed thanks to WGCNA.
- Correlation network between stratification value of gene expressions in severe asthma and its correlation with clinical subgroups will be assessed thanks to WGCNA. This analysis is based on pairwise correlations between genetic variables and clinical variables underlying the amount of overall variance captured by high dimensional gene expression datasets.
- Concerning cost-utility analysis, two strategies of treatment with Benralizumab will be compared: the first one will consider a strategy not using an early blood gene expression signature of Benralizumab response and the second will consider a simulated strategy using an early blood gene expression signature of Benralizumab response
研究者
François-Xavier BLANC
Scientific
Centre Hospitalier Universitaire De Nantes
研究点 (14)
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