Clinical trial NCT04565483: Predictive Signature of Benralizumab Response
Official title: Predictive Signature of Benralizumab Response
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Asthma; Eosinophilic
Severe Asthma
Keywords: severe asthma
therapeutic monoclonal antibody
personalized medicine
transcriptomic
biomarkers
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: Ministère de la Santé - France
First posted: 2020-09-25
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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)


Eligibility 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,
* Documented historical reversibility of FEV1 ≥12% and FEV1 gain ≥ 200 milliliter
* ACQ-7 score ≥ 1,5 at M0.
* ≥ 3 exacerbations in the 12 months prior to screening visit M-1.
* 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:

  * Fractional Exhaled Nitric Oxide (FeNO) \> 25 ppm at inclusion visit or in the 12 months prior to the inclusion visit.
  * Sputum eosinophils ≥ 3% at inclusion visit or in the 12 months prior to the inclusion 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 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
* 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

Primary outcomes:
measure: Predictive value of early blood gene expression signature of Benralizumab
timeFrame: 12 months
Secondary outcomes:
measure: Molecular signature predictive of stabilization
timeFrame: 12 months
measure: The stability of the signature over time
timeFrame: 0 month, 3 months, 6 months and 9 months
measure: The association of gene expression patterns
timeFrame: 12 months
measure: Association of gene expression patterns and clinical characteristics
timeFrame: 0 months
measure: Stratification value of gene expression in severe asthma
timeFrame: 12 months
measure: Scenario-based cost-utility analysis
timeFrame: 12 months
Other outcomes:
Locations:
city: Aix-en-Provence
country: France
facility: Centre hospitalier Intercommunal Aix-en-Provence
city: Angers
country: France
facility: CHU Angers
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Brest
country: France
facility: CHRU Brest
city: Dijon
country: France
facility: CHU Dijon
city: Grenoble
country: France
facility: CHU Grenoble
city: Le Kremlin-Bicêtre
country: France
facility: Hôpital Bicêtre - AP-HP
city: Le Mans
country: France
facility: CH Mans
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Marseille
country: France
facility: Assistance Publique des Hôpitaux de Marseille
city: Montpellier
country: France
facility: CHU Montpellier
city: Nantes
country: France
facility: CHU Nantes
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Hôpital Bichat - AP-HP
city: Rouen
country: France
facility: CHU Rouen
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Suresnes
country: France
facility: Hôpital FOCH
city: Toulouse
country: France
facility: CHU Toulouse
city: Villeurbanne
country: France
facility: Médipôle Hôpital Mutualiste de Villeurbanne
Study officials:
References: