Asthma; EosinophilicPhase 4BENRAPREDNCT04565483
Predictive Signature of Benralizumab Response
A Phase 4 study testing Benralizumab Prefilled Syringe in people with Asthma; Eosinophilic and Severe Asthma, run by Nantes University Hospital at 20 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Asthma; Eosinophilic, Severe Asthma
- What is being tested?
- Benralizumab Prefilled Syringe
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 20 sitesFrance
- Study dates
- 11 Oct 2021to Nov 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
20 sites in 1 country. Contact the study team or a site near you to ask about taking part.
20 sites in 1 country
France20 sites, 16 recruiting
- Recruiting
Centre hospitalier Intercommunal Aix-en-Provence
Aix-en-Provence
Youssef TRIGUI, MD-PHD
- Recruiting
CHU Angers
Angers
Hakima OUKSEL, MD
- Recruiting
CHU Bordeaux
Bordeaux
Pierre-Olivier GIRODET, MD-PHD
- Recruiting
CHRU Brest
Brest
Raphael LE MAO, MD-PHD
- Recruiting
CHU Dijon
Dijon
Philippe BONNIAUD, MD-PHD
- Recruiting
CHU Grenoble
Grenoble
Christel SAINT-RAYMOND, MD-PHD
- Recruiting
Hôpital Bicêtre - AP-HP
Le Kremlin-Bicêtre
Marc HUMBERT, MD-PHD
- Withdrawn
CH Mans
Le Mans
- Withdrawn
CHU Lille
Lille
- Recruiting
Hospices Civils de Lyon
Lyon
Gilles DEVOUASSOUX, MD-PHD
- Not yet recruiting
Assistance Publique des Hôpitaux de Marseille
Marseille
Pascal CHANEZ, MD-PHD
- Withdrawn
CHU Montpellier
Montpellier
- Recruiting
CHU Nantes
Nantes
François-Xavier BLANC, MD-PHD, +33240165545, xavier.blanc@chu-nantes.fr
- Recruiting
CHR Orléans
Orléans
Sylvie DRUELLE
- Recruiting
Hôpital Bichat - AP-HP
Paris
Camille TAILLE, MD-PHD
- Withdrawn
CHU Rouen
Rouen
- Recruiting
CHU Strasbourg
Strasbourg
Naji KHAYATH, MD
- Recruiting
Hôpital FOCH
Suresnes
Colas TCHERAKIAN, MD-PHD
- Recruiting
CHU Toulouse
Toulouse
Laurent GUILLEMINAULT, PD-PHD
- Recruiting
Médipôle Hôpital Mutualiste de Villeurbanne
Villeurbanne
Jean-Marc DOT, MD-PHD
About this study
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)
- Conditions
- Asthma; Eosinophilic, Severe Asthma
- Being tested
- Benralizumab Prefilled Syringe
- Keywords
- severe asthma, therapeutic monoclonal antibody, personalized medicine, transcriptomic, biomarkers
- Medical subject headings
- Pulmonary Eosinophilia, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Benralizumab Prefilled SyringeDrug
Also called Transcriptomic
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.
| Study group | Role | What they receive |
|---|---|---|
| BENRALIZUMAB | Experimental | 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. Receives: Drug: Benralizumab Prefilled Syringe |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 months
Secondary outcomes (6)
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.
Measured: 12 months
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).
Measured: 0 month, 3 months, 6 months and 9 months
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.
Measured: 12 months
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.
Measured: 0 months
Stratification value of gene expression in severe asthma
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.
Measured: 12 months
Scenario-based cost-utility analysis
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2020
- Study start11 Oct 2021
- Primary completionOct 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asthma; EosinophilicStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca, Ministère de la Santé - France
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04565483
- Sponsor's protocol ID
- RC19_0292
- Acronym
- BENRAPRED
- Status last verified
- Apr 2024
- First submitted
- 21 Sep 2020
- Last updated
- 26 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictive Signature of Benralizumab Response
- ClinicalTrials.gov ID
- NCT04565483
- Acronym / sponsor ID
- BENRAPRED / RC19_0292
- Conditions
- Asthma; Eosinophilic, Severe Asthma
- Keywords
- severe asthma, therapeutic monoclonal antibody, personalized medicine, transcriptomic, biomarkers
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Collaborators
- AstraZeneca, Ministère de la Santé - France
- Study start
- 11 Oct 2021 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 25 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BENRALIZUMAB | Experimental | Drug: Benralizumab Prefilled SyringePatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients between 18 and 75 years old.
- Patients diagnosed with severe asthma (Chung and al, Eur Respir J 2014), i.e.:
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Benralizumab Prefilled SyringeAlso: TranscriptomicPatients 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 |
Primary outcome
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).
6 secondary outcomes
Molecular signature predictive of stabilization
Time frame: 12 months
The stability of the signature over time
Time frame: 0 month, 3 months, 6 months and 9 months
The association of gene expression patterns
Time frame: 12 months
Association of gene expression patterns and clinical characteristics
Time frame: 0 months
Stratification value of gene expression in severe asthma
Time frame: 12 months
Scenario-based cost-utility analysis
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Benralizumab Prefilled Syringe in people with Asthma; Eosinophilic and Severe Asthma, run by Nantes University Hospital at 20 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact François-Xavier BLANC, MD-PHD (+33240165545, xavier.blanc@chu-nantes.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Predictive value of early blood gene expression signature of Benralizumab (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2024.