Clinical trial NCT03976310: CT Air-trapping for the Early Identification of Benralizumab Responders Among Eosinophilic Asthma Patients
Official title: Computed Tomography Air-trapping Characterisation for the Early Identification of Benralizumab Responders Among Eosinophilic Asthma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2019-06-06
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This single arm protocol will study individual patient responses to 12 months of benralizumab treatment and early means of detecting them. The model is a prognostic study that will use information detected via baseline quantitative thoracic computed tomography for predicting improvement in exacerbation rate 52 weeks after the start of treatment.
Primary purpose: DIAGNOSTIC

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: The prognositc value (sensitivity) of baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate
timeFrame: 52 weeks
measure: The prognositc value (specificity) of baseline expiratory to inspiratory mean lung density (MLDe/i) for predicting improvement in exacerbation rate
timeFrame: 52 weeks
Secondary outcomes:
measure: 52E: the number of exacerbations occurring during follow-up
timeFrame: 52 weeks
measure: 52cFEV1 pre BD: The change in forced expiratory volume in 1 second (FEV1) pre BD from baseline
timeFrame: 52 weeks
measure: 52cACQ: The change from baseline in the ACQ score
timeFrame: 52 weeks
measure: 52CI: A clinical improvement score
timeFrame: 52 weeks
measure: Concomitant medication use
timeFrame: 52 weeks
measure: The Asthma Control Questionnaire
timeFrame: Week 0
measure: The Asthma Control Questionnaire
timeFrame: Week 24
measure: The Asthma Control Questionnaire
timeFrame: Week 52
measure: The SNOT22 Questionnaire
timeFrame: Week 0
measure: The SNOT22 Questionnaire
timeFrame: Week 24
measure: The SNOT22 Questionnaire
timeFrame: Week 52
measure: The Asthma Quality of Life Questionnaire (AQLQ)
timeFrame: Week 0
measure: The Asthma Quality of Life Questionnaire (AQLQ)
timeFrame: Week 24
measure: The Asthma Quality of Life Questionnaire (AQLQ)
timeFrame: Week 52
measure: Functional residual lung capacity
timeFrame: Week 0
measure: Functional residual lung capacity
timeFrame: Week 52
measure: Residual lung volume
timeFrame: Week 0
measure: Residual lung volume
timeFrame: Week 52
measure: The ratio of residual volume over total lung capacity
timeFrame: Week 0
measure: The ratio of residual volume over total lung capacity
timeFrame: Week 52
measure: Pre-bronchodilator forced expiratory volume in 1 second (litres)
timeFrame: Week 0
measure: Pre-bronchodilator forced expiratory volume in 1 second (litres)
timeFrame: Week 24
measure: Pre-bronchodilator forced expiratory volume in 1 second (litres)
timeFrame: Week 52
measure: Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
timeFrame: Week 0
measure: Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
timeFrame: Week 24
measure: Pre-bronchodilator forced expiratory volume in 1 second (% predicted)
timeFrame: Week 52
measure: Pre-bronchodilator forced vital capacity (litres)
timeFrame: Week 0
measure: Pre-bronchodilator forced vital capacity (litres)
timeFrame: Week 24
measure: Pre-bronchodilator forced vital capacity (litres)
timeFrame: Week 52
measure: Pre-bronchodilator forced vital capacity (% predicted)
timeFrame: Week 0
measure: Pre-bronchodilator forced vital capacity (% predicted)
timeFrame: Week 24
measure: Pre-bronchodilator forced vital capacity (% predicted)
timeFrame: Week 52
measure: Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
timeFrame: Week 0
measure: Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
timeFrame: Week 24
measure: Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity
timeFrame: Week 52
measure: Post-bronchodilator forced expiratory volume in 1 second (litres)
timeFrame: Week 0
measure: Post-bronchodilator forced expiratory volume in 1 second (litres)
timeFrame: Week 24
measure: Post-bronchodilator forced expiratory volume in 1 second (litres)
timeFrame: Week 52
measure: Post-bronchodilator forced expiratory volume in 1 second (% predicted)
timeFrame: Week 0
measure: Post-bronchodilator forced expiratory volume in 1 second (% predicted)
timeFrame: Week 24
measure: Post-bronchodilator forced expiratory volume in 1 second (% predicted)
timeFrame: Week 52
measure: Complete blood count
timeFrame: Week 0
measure: Complete blood count
timeFrame: Week 24
measure: Complete blood count
timeFrame: Week 52
measure: Club cell secretory protein (CCSP) (ng / ml)
timeFrame: Week 0
measure: Club cell secretory protein (CCSP) (ng / ml)
timeFrame: Week 52
measure: The ratio of expiratory to inspiratory mean lung density
timeFrame: Week 0
measure: The ratio of expiratory to inspiratory mean lung density
timeFrame: Week 24
measure: The ratio of expiratory to inspiratory mean lung density
timeFrame: Week 48
measure: LAA-850: The % lung attenuation area at -850 hounsfield units
timeFrame: Week 0
measure: LAA-850: The % lung attenuation area at -850 hounsfield units
timeFrame: Week 24
measure: LAA-850: The % lung attenuation area at -850 hounsfield units
timeFrame: Week 48
measure: The fractal dimension of LAA-850
timeFrame: Week 0
measure: The fractal dimension of LAA-850
timeFrame: Week 24
measure: The fractal dimension of LAA-850
timeFrame: Week 48
measure: LAA-950: The % lung attenuation area at -950 hounsfield units
timeFrame: Week 0
measure: LAA-950: The % lung attenuation area at -950 hounsfield units
timeFrame: Week 24
measure: LAA-950: The % lung attenuation area at -950 hounsfield units
timeFrame: Week 48
measure: The fractal dimension of LAA-950
timeFrame: Week 0
measure: The fractal dimension of LAA-950
timeFrame: Week 24
measure: The fractal dimension of LAA-950
timeFrame: Week 48
measure: Normalized bronchial parietal thickness
timeFrame: Week 0
measure: Normalized bronchial parietal thickness
timeFrame: Week 24
measure: Normalized bronchial parietal thickness
timeFrame: Week 48
measure: Thickness of the sinus mucosa
timeFrame: Week 0
measure: Thickness of the sinus mucosa
timeFrame: Week 48
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique - Hopitaux de Marseille
city: Montpellier
country: France
facility: University Hospitals of Montpellier
Study officials:
affiliation: University Hospitals of Montpellier, France
name: Sébastien Bommart, MD PhD
role: STUDY_DIRECTOR
References: