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.
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
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
59
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.
Assistance Publique - Hopitaux de Marseille
Marseille, France
University Hospitals of Montpellier
Montpellier, France
The prognositc value (sensitivity) of baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate
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.
Time frame: 52 weeks
The prognositc value (specificity) of baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate
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.
Time frame: 52 weeks
52E: the number of exacerbations occurring during follow-up
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.
Time frame: 52 weeks
52cFEV1 pre BD: The change in forced expiratory volume in 1 second (FEV1) pre BD from baseline
Time frame: 52 weeks
52cACQ: The change from baseline in the ACQ score
'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.
Time frame: 52 weeks
52CI: A clinical improvement score
52CI: A clinical improvement score starting at zero and where points are added based on the following criteria: * 52E = 0 or 1 non-admitting† exacerbation (+1 point); * 52cFEV1 pre BD \> 300 ml in asthma patients (+1 point); * 52cACQ \> 0.5 (+1 point).
Time frame: 52 weeks
Concomitant medication use
Time frame: 52 weeks
The Asthma Control Questionnaire
'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.
Time frame: Week 0
The Asthma Control Questionnaire
'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.
Time frame: Week 24
The Asthma Control Questionnaire
'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.
Time frame: Week 52
The SNOT22 Questionnaire
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).
Time frame: Week 0
The SNOT22 Questionnaire
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).
Time frame: Week 24
The SNOT22 Questionnaire
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).
Time frame: Week 52
The Asthma Quality of Life Questionnaire (AQLQ)
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).
Time frame: Week 0
The Asthma Quality of Life Questionnaire (AQLQ)
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).
Time frame: Week 24
The Asthma Quality of Life Questionnaire (AQLQ)
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).
Time frame: Week 52
Functional residual lung capacity
Time frame: Week 0
Functional residual lung capacity
Time frame: Week 52
Residual lung volume
Time frame: Week 0
Residual lung volume
Time frame: Week 52
The ratio of residual volume over total lung capacity
Time frame: Week 0
The ratio of residual volume over total lung capacity
Time frame: Week 52
Pre-bronchodilator forced expiratory volume in 1 second (litres)
Time frame: Week 0
Pre-bronchodilator forced expiratory volume in 1 second (litres)
Time frame: Week 24
Pre-bronchodilator forced expiratory volume in 1 second (litres)
Time frame: Week 52
Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
Time frame: Week 0
Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
Time frame: Week 24
Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
Time frame: Week 52
Pre-bronchodilator forced vital capacity (litres)
Time frame: Week 0
Pre-bronchodilator forced vital capacity (litres)
Time frame: Week 24
Pre-bronchodilator forced vital capacity (litres)
Time frame: Week 52
Pre-bronchodilator forced vital capacity (% predicted)
Time frame: Week 0
Pre-bronchodilator forced vital capacity (% predicted)
Time frame: Week 24
Pre-bronchodilator forced vital capacity (% predicted)
Time frame: Week 52
Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
Time frame: Week 0
Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
Time frame: Week 24
Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
Time frame: Week 52
Post-bronchodilator forced expiratory volume in 1 second (litres)
Time frame: Week 0
Post-bronchodilator forced expiratory volume in 1 second (litres)
Time frame: Week 24
Post-bronchodilator forced expiratory volume in 1 second (litres)
Time frame: Week 52
Post-bronchodilator forced expiratory volume in 1 second (% predicted)
Time frame: Week 0
Post-bronchodilator forced expiratory volume in 1 second (% predicted)
Time frame: Week 24
Post-bronchodilator forced expiratory volume in 1 second (% predicted)
Time frame: Week 52
Complete blood count
Time frame: Week 0
Complete blood count
Time frame: Week 24
Complete blood count
Time frame: Week 52
Club cell secretory protein (CCSP) (ng / ml)
Time frame: Week 0
Club cell secretory protein (CCSP) (ng / ml)
Time frame: Week 52
The ratio of expiratory to inspiratory mean lung density
Time frame: Week 0
The ratio of expiratory to inspiratory mean lung density
Time frame: Week 24
The ratio of expiratory to inspiratory mean lung density
Time frame: Week 48
LAA-850: The % lung attenuation area at -850 hounsfield units
Time frame: Week 0
LAA-850: The % lung attenuation area at -850 hounsfield units
Time frame: Week 24
LAA-850: The % lung attenuation area at -850 hounsfield units
Time frame: Week 48
The fractal dimension of LAA-850
Time frame: Week 0
The fractal dimension of LAA-850
Time frame: Week 24
The fractal dimension of LAA-850
Time frame: Week 48
LAA-950: The % lung attenuation area at -950 hounsfield units
Time frame: Week 0
LAA-950: The % lung attenuation area at -950 hounsfield units
Time frame: Week 24
LAA-950: The % lung attenuation area at -950 hounsfield units
Time frame: Week 48
The fractal dimension of LAA-950
Time frame: Week 0
The fractal dimension of LAA-950
Time frame: Week 24
The fractal dimension of LAA-950
Time frame: Week 48
Normalized bronchial parietal thickness
From bronchial morphometry characterization on computed tomography scan
Time frame: Week 0
Normalized bronchial parietal thickness
From bronchial morphometry characterization on computed tomography scan
Time frame: Week 24
Normalized bronchial parietal thickness
From bronchial morphometry characterization on computed tomography scan
Time frame: Week 48
Thickness of the sinus mucosa
Time frame: Week 0
Thickness of the sinus mucosa
Time frame: Week 48
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