Predictive Signature of Benralizumab Response
Predictive Signature of Benralizumab Response
The objective of the study is 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.

 This trial is a French, multicenter and no-randomized trial. Patients enrolled will be
 clinically followed for 16 months (the treatment period: 12 months and 1 month follow-up; 6
 clinical visit on site and in phone call at 13 months)
Inclusion Criteria:

 -  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,

 -  Pre-BronchoDilatator (BD) FEV1 <80% of the predicted value at M-1.

 -  Documented historical reversibility of FEV1 ≥12% and FEV1 gain ≥ 200 milliliter

 -  ACQ-7 score ≥ 1,5 at M-1 and M0.

 -  ≥ 3 exacerbations in the 12 months prior to screening visit M-1.

 -  Eosinophil blood count ≥ 0,3 G/L at screening visit or in the 12 months prior to the
 screening 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:

 -  Fractional Exhaled Nitric Oxide (FeNO) > 25 ppm at screening visit or in the 12
 months prior to the screening visit.

 -  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

 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, Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia
 (DIPNEC), asthma/ chronic obstructive pulmonary disease (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, curators or safeguard of justice