Predictive Signature of Benralizumab Response

• Status: Recruiting
• Trial end date: 2024-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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)

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nantes University Hospital
• Collaborators: AstraZeneca; Ministère de la Santé - France
• Treatments: Benralizumab

Criteria

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