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Trial record 1 of 1 for:    BENRAPRED
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Predictive Signature of Benralizumab Response (BENRAPRED)

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ClinicalTrials.gov Identifier: NCT04565483
Recruitment Status : Recruiting
First Posted : September 25, 2020
Last Update Posted : March 21, 2023
Sponsor:
Collaborators:
AstraZeneca
Ministère de la Santé - France
Information provided by (Responsible Party):
Nantes University Hospital

Study Description
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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)


Condition or disease Intervention/treatment Phase
Asthma; Eosinophilic Severe Asthma Drug: Benralizumab Prefilled Syringe Phase 4

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 220 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Predictive Signature of Benralizumab Response
Actual Study Start Date : October 11, 2021
Estimated Primary Completion Date : March 2024
Estimated Study Completion Date : April 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: BENRALIZUMAB
Patients receive BENRALIZUMAB if they meet the criteria for inclusion and non-inclusion at the inclusion visit. Injections take place at the inclusion visit, at 1 month, 2 months, 4 months, 6 months, 8 months, 10 months and 12 months.
 Drug: Benralizumab Prefilled Syringe
Patients receive BENRALIZUMAB if they meet the criteria for inclusion and non-inclusion at the inclusion visit. Injections take place at the inclusion visit, at 1 month, 2 months, 4 months, 6 months, 8 months, 10 months and 12 months.
Other Name: Transcriptomic


Outcome Measures
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Primary Outcome Measures :
  1. Predictive value of early blood gene expression signature of Benralizumab [ Time Frame: 12 months ]
    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. We will evaluate an early blood gene expression signature of Benralizumab response through a clinically relevant reduction of the number of exacerbations at month 12 (M12).


Secondary Outcome Measures :
  1. Molecular signature predictive of stabilization [ Time Frame: 12 months ]
    To establish at M0 (baseline) a molecular signature predictive of stabilization in severe asthmatic patients treated by Benralizumab. 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. The definition of stable class of patients (low category) is used as a target for the prediction. The methods used for the primary objective are applied to secondary objective using similar input data on a different 3-class prediction target.

  2. The stability of the signature over time [ Time Frame: 0 month, 3 months, 6 months and 9 months ]
    To evaluate the stability of the signature over time (from early at M0, M3, to late prediction at M6 and M9) considering patient trajectories. 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).

  3. The association of gene expression patterns [ Time Frame: 12 months ]
    To evaluate the association of gene expression patterns with both objective and subjective improvement. 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 forced expiratory volume at one second (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.

  4. Association of gene expression patterns and clinical characteristics [ Time Frame: 0 months ]
    To evaluate association of gene expression patterns at M0 (baseline) and clinical characteristics of frequent exacerbations. Correlations network between blood gene expression at M0 and clinical characteristics of frequent exacerbations will be assessed thanks to WGCNA.

  5. Stratification value of gene expression in severe asthma [ Time Frame: 12 months ]
    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. 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.

  6. Scenario-based cost-utility analysis [ Time Frame: 12 months ]
    To conduct a scenario-based cost-utility analysis.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 second will consider a simulated strategy using an early blood gene expression signature of Benralizumab response.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04565483


Contacts
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Contact: François-Xavier BLANC, MD-PHD +33240165545 xavier.blanc@chu-nantes.fr

Locations
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France
CHU Angers Recruiting
Angers, France
Contact: Hakima OUKSEL, MD         
CHU Bordeaux Not yet recruiting
Bordeaux, France
Contact: Pierre-Olivier GIRODET, MD-PHD         
CHU Dijon Recruiting
Dijon, France
Contact: Philippe BONNIAUD, MD-PHD         
CHU Grenoble Recruiting
Grenoble, France
Contact: Christel SAINT-RAYMOND, MD-PHD         
Hôpital Bicêtre - AP-HP Recruiting
Le Kremlin-Bicêtre, France
Contact: Marc HUMBERT, MD-PHD         
CH Mans Not yet recruiting
Le Mans, France
Contact: François GOUPIL, MD         
CHU Lille Not yet recruiting
Lille, France
Contact: Stéphanie FRY, MD         
Hospices Civils de Lyon Recruiting
Lyon, France
Contact: Gilles DEVOUASSOUX, MD-PHD         
Assistance Publique des Hôpitaux de Marseille Not yet recruiting
Marseille, France
Contact: Pascal CHANEZ, MD-PHD         
CHU Montpellier Not yet recruiting
Montpellier, France
Contact: Arnaud BOURDIN, MD-PHD         
CHU Nantes Recruiting
Nantes, France
Contact: François-Xavier BLANC, MD-PHD    +33240165545    xavier.blanc@chu-nantes.fr   
Hôpital Bichat - AP-HP Recruiting
Paris, France
Contact: Camille TAILLE, MD-PHD         
CHU Rouen Not yet recruiting
Rouen, France
Contact: Guillaume MAHAY, MD         
CHU Strasbourg Not yet recruiting
Strasbourg, France
Contact: Naji KHAYATH, MD         
Hôpital FOCH Recruiting
Suresnes, France
Contact: Antoine MAGNAN, MD-PHD         
CHU Toulouse Recruiting
Toulouse, France
Contact: Laurent GUILLEMINAULT, PD-PHD         
Sponsors and Collaborators
Nantes University Hospital
AstraZeneca
Ministère de la Santé - France
More Information
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Responsible Party: Nantes University Hospital
ClinicalTrials.gov Identifier: NCT04565483    
Other Study ID Numbers: RC19_0292
First Posted: September 25, 2020    Key Record Dates
Last Update Posted: March 21, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nantes University Hospital:
severe asthma
therapeutic monoclonal antibody
personalized medicine
transcriptomic
biomarkers
Additional relevant MeSH terms:
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Asthma
Pulmonary Eosinophilia
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
 Immune System Diseases
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents