- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03976310
CT Air-trapping for the Early Identification of Benralizumab Responders Among Eosinophilic Asthma Patients (BenraliScan)
Computed Tomography Air-trapping Characterisation for the Early Identification of Benralizumab Responders Among Eosinophilic Asthma Patients
BenraliScan aims to obtain thoracic computed tomography imaging data to predict the future level of patient response to a monoclonal antibody. Because the clinical responses under study can take many months to manifest, early identification of patients most-likely to benefit from treatment and treatment rule-out for others will save considerable time for everybody involved.
The primary objective of BenraliScan is to determine the prognostic value (sensitivity, specificity, positive predictive value, negative predictive value) of air-trapping measures (Expiratory/Inspiratory ratios for Mean Lung Density (MLDe/i)) detected via quantitative thoracic computed tomography at baseline for improvement in exacerbation rate (the presence of a ≥50% reduction in baseline exacerbation rate versus the absence of a ≥50% reduction in baseline exacerbation rate) at 52 weeks among eosinophilic asthma patients treated with Benralizumab.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Secondary, exploratory objectives include:
- To describe clinical improvement category sub-groups (e.g. non-responders versus strong responders) in terms of: target concomitant medication usage, symptomology, quality of life (questionnaires), exacerbation rates (and other adverse events) and lung function parameters, differential blood counts, serum club cell secretory protein (CCSP) levels, other quantitative thoracic computed tomography (QTCT) variables, sinus mucosal thickness.
- To perform exploratory, prognostic-value studies (including but not limited to prognostic variables derived from changes occurring over 24 weeks and from clustering or factor mining at baseline and 24 weeks). These exploratory studies will include (but are not necessarily limited to) estimating the sensitivity/specificity of baseline/early imaging variables (or combination thereof) for predicting clinical response variables.
- To describe the prognostic categories (e.g. predicted non-responder versus predicted responder) found in terms of: clinical improvement, target concomitant medication usage, symptomology, quality of life (questionnaires), exacerbation rates (and other adverse events) and lung function parameters, differential blood counts, serum CCSP levels, other QTCT variables, sinus mucosal thickness.
- To create a centralised image library associated with the study.
- To verify the reproducibility of the relationships found between mean lung density (upper and lower lung, inspiratory and expiratory), the fractal dimension of -850 HU segmentations, and clinical variables found during the SCANN'AIR study (NCT03102749).
- To explore the association between bronchial homothety curves (the homothety of two consecutive bronchial measurements as a function of bronchial generation) and disease severity/progression.
- To monitor patient safety throughout the study.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Marseille, France, 13915
- Assistance Publique - Hopitaux de Marseille
-
Montpellier, France, 34295
- University Hospitals of Montpellier
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Understanding and acceptance of the protocol
- The patient has given his/her informed consent and signed the consent form
- Affiliation with or beneficiary of the French national health insurance system
- Female and male patients aged 18 to 75 years (inclusively) with a history of physician-diagnosed severe asthma (according to GINA criteria) requiring treatment with high-dose inhaled corticosteroid (ICS) plus long-acting beta-agonists for at least 12 months prior to inclusion
- Documented current treatment with high daily doses of ICS (>1000 µg equivalent beclomethasone) plus at least one other asthma controller for at least 6 months prior to inclusion
- History of at least 2 asthma exacerbations while on ICS plus another asthma controller that required treatment with systemic corticosteroids (any administration route) in the 12 months prior to inclusion. For patients receiving corticosteroids as a maintenance therapy, the corticosteroid treatment for the exacerbation is defined as a temporary increase in their maintenance dose.
- Uncontrolled disease (Asthma Control Questionnaire >1.5)
- Pre bronchodilator forced expiratory volume at 1 second (% predicted) between 40% and 85%, established according to the NHANESIII criteria
- Blood eosinophilia ≥ 300 cells / µl at least once during the previous 12 months -OR- blood eosinophilia ≥ 300 cells / µl upon inclusion
- Women of childbearing potential must use at least one acceptable and effective form of birth control
- Weight ≥ 40 kg
Exclusion Criteria:
- Other respiratory diseases or associated lung infections
- Patient treated with a monoclonal antibody in the 5 months preceding inclusion
- Patient who participated in a therapeutic study in the month prior to inclusion
- Patient deprived of liberty by judicial or administrative decision
- Major (adult) protected by the law (under any kind of guardianship)
- Patient in an exclusion period determined by another protocol
- Patient who participated in another research protocol with X-ray exposure in the past 12 months
- Patient who has already participated in the present protocol
- Hypersensitivity to benralizumab or to any of the excipients: histidine, histidine hydrochloride monohydrate, trehalose dehydrate, polysorbate 20 and water for injections
- Exacerbation, antibiotics, or non-maintenance systemic steroids during the 6 weeks prior to inclusion
- Subjects with untreated helminthic parasitic infection
- Lactating or pregnant* females or females who intend to become pregnant
- Subjects with a history of anaphylaxis to any biologic therapy
- Subjects taking immunosuppressive medications (except oral prednisone and inhaled and topical corticosteroids)
- Subjects with intercurrent illnesses (eg, viral illnesses) that may compromise the safety of the subject
- Subjects who are febrile (≥ 38°C)
- Currently smoking or smoking history ≥ 20 pack years
- Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the subject is in remission and curative therapy was completed at least 12 months prior to the date of informed consent, and assent when applicable was obtained
- Subjects who have had other malignancies are eligible provided that the subject is in remission and curative therapy was completed at least 5 years prior to the date of informed consent, and assent when applicable, was obtained
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: The study population
The study population corresponds to severe eosinophilic asthma patients (see eligibility criteria).
|
Benralizumab is administered for 48 weeks (week 0 to week 48) every 4 weeks for the first 3 injections (30 mg sc per injection), and then every 8 weeks for the following 5 injections.
Computed tomography of the thorax is performed at the beginning (week 0), middle (week 24) and towards the end (week 48) of Benralizumab therapy.
A sinus scan is also added on weeks 0 and 48.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The prognositc value (sensitivity) of baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate
Time Frame: 52 weeks
|
The sensitivity and specificity of the baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate (the presence of a ≥50% reduction in baseline exacerbation rate versus the absence of a ≥50% reduction in baseline exacerbation rate) at week 52.
|
52 weeks
|
The prognositc value (specificity) of baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate
Time Frame: 52 weeks
|
The sensitivity and specificity of the baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate (the presence of a ≥50% reduction in baseline exacerbation rate versus the absence of a ≥50% reduction in baseline exacerbation rate) at week 52.
|
52 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
52E: the number of exacerbations occurring during follow-up
Time Frame: 52 weeks
|
An exacerbation is defined as follows: worsening of symptoms (increased shortness of breath, cough, sputum, with or without fever) which necessitates unscheduled healthcare resource use, a need for >48h of oral corticosteroids.
For oral steroids, a minimal dose of 0.25 mg/kg is required.
For patients taking oral steroids on a long term basis, at least a doubling dose for 2 days is required.
|
52 weeks
|
52cFEV1 pre BD: The change in forced expiratory volume in 1 second (FEV1) pre BD from baseline
Time Frame: 52 weeks
|
52 weeks
|
|
52cACQ: The change from baseline in the ACQ score
Time Frame: 52 weeks
|
'ACQ' refers to the Asthma Control Questionnaire: The ACQ-6 is a shortened version of the ACQ that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and SABA use) omitting the FEV1 measurement from the original ACQ score.
Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions.
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled).
The mean ACQ-6 score is the mean of the responses.
Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and <1.5 indicate partly controlled asthma, and a score ≥1.5 indicates not well controlled asthma.
Individual changes of at least 0.5 are considered to be clinically meaningful.
|
52 weeks
|
52CI: A clinical improvement score
Time Frame: 52 weeks
|
52CI: A clinical improvement score starting at zero and where points are added based on the following criteria:
|
52 weeks
|
Concomitant medication use
Time Frame: 52 weeks
|
52 weeks
|
|
The Asthma Control Questionnaire
Time Frame: Week 0
|
'ACQ' refers to the Asthma Control Questionnaire: The ACQ-6 is a shortened version of the ACQ that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and SABA use) omitting the FEV1 measurement from the original ACQ score.
Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions.
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled).
The mean ACQ-6 score is the mean of the responses.
Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and <1.5 indicate partly controlled asthma, and a score ≥1.5 indicates not well controlled asthma.
Individual changes of at least 0.5 are considered to be clinically meaningful.
|
Week 0
|
The Asthma Control Questionnaire
Time Frame: Week 24
|
'ACQ' refers to the Asthma Control Questionnaire: The ACQ-6 is a shortened version of the ACQ that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and SABA use) omitting the FEV1 measurement from the original ACQ score.
Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions.
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled).
The mean ACQ-6 score is the mean of the responses.
Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and <1.5 indicate partly controlled asthma, and a score ≥1.5 indicates not well controlled asthma.
Individual changes of at least 0.5 are considered to be clinically meaningful.
|
Week 24
|
The Asthma Control Questionnaire
Time Frame: Week 52
|
'ACQ' refers to the Asthma Control Questionnaire: The ACQ-6 is a shortened version of the ACQ that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing, and SABA use) omitting the FEV1 measurement from the original ACQ score.
Patients are asked to recall how their asthma has been during the previous week by responding to one bronchodilator use question and 5 symptom questions.
Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled).
The mean ACQ-6 score is the mean of the responses.
Mean scores of ≤0.75 indicate well-controlled asthma, scores between 0.75 and <1.5 indicate partly controlled asthma, and a score ≥1.5 indicates not well controlled asthma.
Individual changes of at least 0.5 are considered to be clinically meaningful.
|
Week 52
|
The SNOT22 Questionnaire
Time Frame: Week 0
|
The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110 (higher scores indicate poorer outcomes).
|
Week 0
|
The SNOT22 Questionnaire
Time Frame: Week 24
|
The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110 (higher scores indicate poorer outcomes).
|
Week 24
|
The SNOT22 Questionnaire
Time Frame: Week 52
|
The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110 (higher scores indicate poorer outcomes).
|
Week 52
|
The Asthma Quality of Life Questionnaire (AQLQ)
Time Frame: Week 0
|
The Asthma Quality of Life Questionnaire (AQLQ) is a 32-item, 4-domain questionnaire with a 2-week recall period.
Each item is scored using a 7-point likert scale where scores range from 1 to 7 and higher scores indicate higher quality of life.
Simple means are used to calculate the overall AQLQ score (as well as domain scores).
|
Week 0
|
The Asthma Quality of Life Questionnaire (AQLQ)
Time Frame: Week 24
|
The Asthma Quality of Life Questionnaire (AQLQ) is a 32-item, 4-domain questionnaire with a 2-week recall period.
Each item is scored using a 7-point likert scale where scores range from 1 to 7 and higher scores indicate higher quality of life.
Simple means are used to calculate the overall AQLQ score (as well as domain scores).
|
Week 24
|
The Asthma Quality of Life Questionnaire (AQLQ)
Time Frame: Week 52
|
The Asthma Quality of Life Questionnaire (AQLQ) is a 32-item, 4-domain questionnaire with a 2-week recall period.
Each item is scored using a 7-point likert scale where scores range from 1 to 7 and higher scores indicate higher quality of life.
Simple means are used to calculate the overall AQLQ score (as well as domain scores).
|
Week 52
|
Functional residual lung capacity
Time Frame: Week 0
|
Week 0
|
|
Functional residual lung capacity
Time Frame: Week 52
|
Week 52
|
|
Residual lung volume
Time Frame: Week 0
|
Week 0
|
|
Residual lung volume
Time Frame: Week 52
|
Week 52
|
|
The ratio of residual volume over total lung capacity
Time Frame: Week 0
|
Week 0
|
|
The ratio of residual volume over total lung capacity
Time Frame: Week 52
|
Week 52
|
|
Pre-bronchodilator forced expiratory volume in 1 second (litres)
Time Frame: Week 0
|
Week 0
|
|
Pre-bronchodilator forced expiratory volume in 1 second (litres)
Time Frame: Week 24
|
Week 24
|
|
Pre-bronchodilator forced expiratory volume in 1 second (litres)
Time Frame: Week 52
|
Week 52
|
|
Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
Time Frame: Week 0
|
Week 0
|
|
Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
Time Frame: Week 24
|
Week 24
|
|
Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
Time Frame: Week 52
|
Week 52
|
|
Pre-bronchodilator forced vital capacity (litres)
Time Frame: Week 0
|
Week 0
|
|
Pre-bronchodilator forced vital capacity (litres)
Time Frame: Week 24
|
Week 24
|
|
Pre-bronchodilator forced vital capacity (litres)
Time Frame: Week 52
|
Week 52
|
|
Pre-bronchodilator forced vital capacity (% predicted)
Time Frame: Week 0
|
Week 0
|
|
Pre-bronchodilator forced vital capacity (% predicted)
Time Frame: Week 24
|
Week 24
|
|
Pre-bronchodilator forced vital capacity (% predicted)
Time Frame: Week 52
|
Week 52
|
|
Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
Time Frame: Week 0
|
Week 0
|
|
Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
Time Frame: Week 24
|
Week 24
|
|
Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
Time Frame: Week 52
|
Week 52
|
|
Post-bronchodilator forced expiratory volume in 1 second (litres)
Time Frame: Week 0
|
Week 0
|
|
Post-bronchodilator forced expiratory volume in 1 second (litres)
Time Frame: Week 24
|
Week 24
|
|
Post-bronchodilator forced expiratory volume in 1 second (litres)
Time Frame: Week 52
|
Week 52
|
|
Post-bronchodilator forced expiratory volume in 1 second (% predicted)
Time Frame: Week 0
|
Week 0
|
|
Post-bronchodilator forced expiratory volume in 1 second (% predicted)
Time Frame: Week 24
|
Week 24
|
|
Post-bronchodilator forced expiratory volume in 1 second (% predicted)
Time Frame: Week 52
|
Week 52
|
|
Complete blood count
Time Frame: Week 0
|
Week 0
|
|
Complete blood count
Time Frame: Week 24
|
Week 24
|
|
Complete blood count
Time Frame: Week 52
|
Week 52
|
|
Club cell secretory protein (CCSP) (ng / ml)
Time Frame: Week 0
|
Week 0
|
|
Club cell secretory protein (CCSP) (ng / ml)
Time Frame: Week 52
|
Week 52
|
|
The ratio of expiratory to inspiratory mean lung density
Time Frame: Week 0
|
Week 0
|
|
The ratio of expiratory to inspiratory mean lung density
Time Frame: Week 24
|
Week 24
|
|
The ratio of expiratory to inspiratory mean lung density
Time Frame: Week 48
|
Week 48
|
|
LAA-850: The % lung attenuation area at -850 hounsfield units
Time Frame: Week 0
|
Week 0
|
|
LAA-850: The % lung attenuation area at -850 hounsfield units
Time Frame: Week 24
|
Week 24
|
|
LAA-850: The % lung attenuation area at -850 hounsfield units
Time Frame: Week 48
|
Week 48
|
|
The fractal dimension of LAA-850
Time Frame: Week 0
|
Week 0
|
|
The fractal dimension of LAA-850
Time Frame: Week 24
|
Week 24
|
|
The fractal dimension of LAA-850
Time Frame: Week 48
|
Week 48
|
|
LAA-950: The % lung attenuation area at -950 hounsfield units
Time Frame: Week 0
|
Week 0
|
|
LAA-950: The % lung attenuation area at -950 hounsfield units
Time Frame: Week 24
|
Week 24
|
|
LAA-950: The % lung attenuation area at -950 hounsfield units
Time Frame: Week 48
|
Week 48
|
|
The fractal dimension of LAA-950
Time Frame: Week 0
|
Week 0
|
|
The fractal dimension of LAA-950
Time Frame: Week 24
|
Week 24
|
|
The fractal dimension of LAA-950
Time Frame: Week 48
|
Week 48
|
|
Normalized bronchial parietal thickness
Time Frame: Week 0
|
From bronchial morphometry characterization on computed tomography scan
|
Week 0
|
Normalized bronchial parietal thickness
Time Frame: Week 24
|
From bronchial morphometry characterization on computed tomography scan
|
Week 24
|
Normalized bronchial parietal thickness
Time Frame: Week 48
|
From bronchial morphometry characterization on computed tomography scan
|
Week 48
|
Thickness of the sinus mucosa
Time Frame: Week 0
|
Week 0
|
|
Thickness of the sinus mucosa
Time Frame: Week 48
|
Week 48
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Sébastien Bommart, MD PhD, University Hospitals of Montpellier, France
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Immune System Diseases
- Lung Diseases
- Hypersensitivity, Immediate
- Hematologic Diseases
- Bronchial Diseases
- Lung Diseases, Obstructive
- Respiratory Hypersensitivity
- Hypersensitivity
- Leukocyte Disorders
- Eosinophilia
- Hypereosinophilic Syndrome
- Asthma
- Pulmonary Eosinophilia
- Anti-Asthmatic Agents
- Respiratory System Agents
- Benralizumab
Other Study ID Numbers
- RECHMPL18_0016
- 2018-002292-18 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Asthma
-
Vanderbilt University Medical CenterNot yet recruitingAsthma in Children | Asthma Attack | Asthma Acute | Acute Asthma Exacerbation | Asthma; StatusUnited States
-
University of California, San FranciscoCompletedAsthma in Children | Asthma Attack | Asthma Acute | Asthma ChronicUnited States
-
SingHealth PolyclinicsNot yet recruitingAsthma | Asthma in Children | Asthma Attack | Asthma Acute | Asthma Chronic
-
Johann Wolfgang Goethe University HospitalCompleted
-
Universita di VeronaCompleted
-
Parc de Salut MarActive, not recruitingAsthma in Children | Persistent Asthma | Asthma ExacerbationSpain
-
Forest LaboratoriesCompleted
-
Brunel UniversityKarolinska InstitutetUnknown
-
Value Outcomes Ltd.AstraZenecaCompletedAsthma, Bronchial | Bronchial Asthma | Asthma Chronic | Asthma; EosinophilicCzechia
Clinical Trials on 48 weeks of Benralizumab
-
University of Alabama at BirminghamUniversity of Colorado, Denver; National Institute of Diabetes and Digestive... and other collaboratorsCompletedUrologicalUnited States, Canada
-
Mitsubishi Tanabe Pharma CorporationToray Industries, IncCompleted
-
IpsenCompleted
-
Hospital General de México Dr. Eduardo LiceagaCompleted
-
Organon and CoCompletedBenign Prostatic Hyperplasia
-
Organon and CoCompletedAndrogenetic Alopecia
-
Merck Sharp & Dohme LLCCompleted
-
University of AarhusAarhus University Hospital; Regionshospitalet Hammel Neurocenter; Roche Diagnostics and other collaboratorsCompletedCardiac ArrestDenmark, Norway
-
Third Affiliated Hospital, Sun Yat-Sen UniversityCompleted
-
National Taiwan University HospitalNational Science Council, Taiwan; Department of Health, Executive Yuan, R.O...Completed