CT Air-trapping for the Early Identification of Benralizumab Responders Among Eosinophilic Asthma Patients (BenraliScan)

University Hospital Center (CHU)

Status

Completed

Conditions

Asthma

Treatments

Other: Computed tomography

Drug: 48 weeks of Benralizumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03976310

2018-002292-18 (EudraCT Number)

RECHMPL18_0016

Details and patient eligibility

About

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.

Full 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.

Enrollment

59 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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