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

NCT ID: NCT03976310

Last Updated: 2023-07-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-20
• Study Completion Date: 2023-06-09

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.

Conditions

Asthma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

The study population

The study population corresponds to severe eosinophilic asthma patients (see eligibility criteria).

Group Type: OTHER

48 weeks of Benralizumab

Intervention Type: DRUG

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

Intervention Type: OTHER

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.

Interventions

48 weeks of Benralizumab

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.

Intervention Type: DRUG

Computed tomography

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.

Intervention Type: OTHER

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sébastien Bommart, MD PhD

Role: STUDY_DIRECTOR

University Hospitals of Montpellier, France

Locations

Assistance Publique - Hopitaux de Marseille

Marseille, , France

University Hospitals of Montpellier

Montpellier, , France

Countries

France

Other Identifiers

2018-002292-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

RECHMPL18_0016

Identifier Type: -

Identifier Source: org_study_id