Severe asthma MedDRA version: 21.1 Level: LLT Classification code 10068462 Term: Eosinophilic asthma System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Fasenra
Product Name: Benralizumab
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: BENRALIZUMAB
Current Sponsor code: PRD8275546
Concentration unit:
Sponsors
CHU of Nantes
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients between 18 and 75 years old. - Patients diagnosed with severe asthma (Chung and al, Eur Respir J 2014), i.e.: o asthma requiring high doses of ICS (>1000 ?g per day of Beclomethasone or equivalent) associated with LABA and/or systemic corticosteroids to be controlled over one year, o and/or uncontrolled asthma despite the later medications, o and/or a controlled asthma worsening after decreasing medications, - Pre-BD FEV1 25 ppm at screening visit or in the 12 months prior to the screening visit. o Sputum eosinophils ? 3% at screening visit or in the 12 months prior to the screening visit. - Patients who provide written informed consent prior to participation in the study Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 165 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: - Patients diagnosed with difficult-to-treat asthma and/or with asthma differential diagnosis that have not yet been excluded (vocal cord dysfunction, gastroesophageal reflux disease, granulomatous eosinophilic vasculitis, obstructive sleep apnea syndrome, hyperventilation syndrome, allergic broncho-pulmonary aspergillosis, Carrington disease, DIPNEC, asthma/COPD overlap syndrome). - Non-adherent patients to inhaled treatment (ICS + LABA). - Active smokers or former smokers exceeding 20 packs year. - Exacerbation at screening visit M-1. - Exacerbation within the past 4 weeks prior to M0, to avoid confounding effects of a short course of systemic corticosteroids that could bias basal molecular signature. - 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 - Patients requiring other biotherapy than Benralizumab that affects the immune system - 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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.;Secondary Objective: The key secondary objectives of this study are: SO1: To establish at M0 (baseline) a molecular signature predictive of stabilization in severe asthmatic patients treated by Benralizumab. SO2: To evaluate the stability of the signature over time (from early at M0, M3, to late prediction at M6 and M9) considering patient trajectories. SO3: To evaluate the association of gene expression patterns with both objective and subjective improvement. S04: To evaluate association of gene expression patterns at M0 (baseline) and clinical characteristics of frequent exacerbations. SO5: To assess the stratification value of gene expression in severe asthma and its correlation with clinical subgroups and clinically meaningful variables such as number of exacerbations. SO6: To conduct a scenario-based cost-utility analysis. ;Primary end point(s): Evaluation an early blood gene expression signature of Benralizumab response through a clinically relevant reduction of the number of exacerbations at month 12 (M12). ;Timepoint(s) of evaluation of this end point: Blood sample for tha analyse of gene expresssion at baseline, 3 months, 6 months, 9 months and 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): SO1: 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. The methods used for the primary objective (PO) are applied to SO1 using similar input data on a different 3-class prediction target. SO2: 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). SO3: 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 + Asthma Quality of Life Questionnaire (AQLQ) + peak-flow values and expected decrease of Asthma Control Questionnaire-7 items (ACQ-7), -6 items (ACQ-6) scores. SO4: Correlations network between blood gene expression at M0 and clinical characteristics of frequent exacerbations will be assessed thanks to WGCNA. SO5: 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. SO6: 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 | — |
Countries
France
Contacts
Public ContactDirection Recherche, CHU de Nantes
CHU of Nantes
Outcome results
None listed