Predictive Signature of Benralizumab Response (BENRAPRED)

This is an interventional other trial for Asthma; Eosinophilic focused on measuring severe asthma, therapeutic monoclonal antibody, personalized medicine, transcriptomic, biomarkers Read More

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 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).
• 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
• 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, curators or safeguard of justice