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Predictive Signature of Benralizumab Response

ConditionsAsthma; EosinophilicSevere Asthma
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-75
SponsorNantes University Hospital

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

Patients between 18 and 75 years old.

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,

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

  • Benralizumab Prefilled Syringe

    Drug

    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.

Treatment groups

220 Participants
are divided into 1 treatment group
Group A: BENRALIZUMABExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Predictive value of early blood gene expression signature of Benralizumab

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).

Time frame
12 months

Secondary outcomes

1

Molecular signature predictive of stabilization

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.

Time frame
12 months
2

The stability of the signature over time

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).

Time frame
0 month, 3 months, 6 months and 9 months
3

The association of gene expression patterns

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.

Time frame
12 months
4

Association of gene expression patterns and clinical characteristics

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.

Time frame
0 months

Other outcomes

Sponsors and contacts

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Nantes University Hospital

Lead sponsor

AstraZeneca

Collaborator

Ministère de la Santé - France

Collaborator

Source ClinicalTrials.gov
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