Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03976310
Other study ID # RECHMPL18_0016
Secondary ID 2018-002292-18
Status Completed
Phase N/A
First received
Last updated
Start date June 20, 2019
Est. completion date June 9, 2023

Study information

Verified date September 2022
Source University Hospital, Montpellier
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 59
Est. completion date June 9, 2023
Est. primary completion date June 9, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Drug:
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.
Other:
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.

Locations

Country Name City State
France Assistance Publique - Hopitaux de Marseille Marseille
France University Hospitals of Montpellier Montpellier

Sponsors (2)

Lead Sponsor Collaborator
University Hospital, Montpellier AstraZeneca

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. 52 weeks
Primary 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. 52 weeks
Secondary 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. 52 weeks
Secondary 52cFEV1 pre BD: The change in forced expiratory volume in 1 second (FEV1) pre BD from baseline 52 weeks
Secondary 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. 52 weeks
Secondary 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).
52 weeks
Secondary Concomitant medication use 52 weeks
Secondary 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. Week 0
Secondary 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. Week 24
Secondary 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. Week 52
Secondary 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). Week 0
Secondary 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). Week 24
Secondary 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). Week 52
Secondary 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). Week 0
Secondary 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). Week 24
Secondary 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). Week 52
Secondary Functional residual lung capacity Week 0
Secondary Functional residual lung capacity Week 52
Secondary Residual lung volume Week 0
Secondary Residual lung volume Week 52
Secondary The ratio of residual volume over total lung capacity Week 0
Secondary The ratio of residual volume over total lung capacity Week 52
Secondary Pre-bronchodilator forced expiratory volume in 1 second (litres) Week 0
Secondary Pre-bronchodilator forced expiratory volume in 1 second (litres) Week 24
Secondary Pre-bronchodilator forced expiratory volume in 1 second (litres) Week 52
Secondary Pre-bronchodilator forced expiratory volume in 1 second (% predicted) Week 0
Secondary Pre-bronchodilator forced expiratory volume in 1 second (% predicted) Week 24
Secondary Pre-bronchodilator forced expiratory volume in 1 second (% predicted) Week 52
Secondary Pre-bronchodilator forced vital capacity (litres) Week 0
Secondary Pre-bronchodilator forced vital capacity (litres) Week 24
Secondary Pre-bronchodilator forced vital capacity (litres) Week 52
Secondary Pre-bronchodilator forced vital capacity (% predicted) Week 0
Secondary Pre-bronchodilator forced vital capacity (% predicted) Week 24
Secondary Pre-bronchodilator forced vital capacity (% predicted) Week 52
Secondary Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity Week 0
Secondary Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity Week 24
Secondary Pre-bronchodilator forced expiratory volume in 1 second / forced vital capacity Week 52
Secondary Post-bronchodilator forced expiratory volume in 1 second (litres) Week 0
Secondary Post-bronchodilator forced expiratory volume in 1 second (litres) Week 24
Secondary Post-bronchodilator forced expiratory volume in 1 second (litres) Week 52
Secondary Post-bronchodilator forced expiratory volume in 1 second (% predicted) Week 0
Secondary Post-bronchodilator forced expiratory volume in 1 second (% predicted) Week 24
Secondary Post-bronchodilator forced expiratory volume in 1 second (% predicted) Week 52
Secondary Complete blood count Week 0
Secondary Complete blood count Week 24
Secondary Complete blood count Week 52
Secondary Club cell secretory protein (CCSP) (ng / ml) Week 0
Secondary Club cell secretory protein (CCSP) (ng / ml) Week 52
Secondary The ratio of expiratory to inspiratory mean lung density Week 0
Secondary The ratio of expiratory to inspiratory mean lung density Week 24
Secondary The ratio of expiratory to inspiratory mean lung density Week 48
Secondary LAA-850: The % lung attenuation area at -850 hounsfield units Week 0
Secondary LAA-850: The % lung attenuation area at -850 hounsfield units Week 24
Secondary LAA-850: The % lung attenuation area at -850 hounsfield units Week 48
Secondary The fractal dimension of LAA-850 Week 0
Secondary The fractal dimension of LAA-850 Week 24
Secondary The fractal dimension of LAA-850 Week 48
Secondary LAA-950: The % lung attenuation area at -950 hounsfield units Week 0
Secondary LAA-950: The % lung attenuation area at -950 hounsfield units Week 24
Secondary LAA-950: The % lung attenuation area at -950 hounsfield units Week 48
Secondary The fractal dimension of LAA-950 Week 0
Secondary The fractal dimension of LAA-950 Week 24
Secondary The fractal dimension of LAA-950 Week 48
Secondary Normalized bronchial parietal thickness From bronchial morphometry characterization on computed tomography scan Week 0
Secondary Normalized bronchial parietal thickness From bronchial morphometry characterization on computed tomography scan Week 24
Secondary Normalized bronchial parietal thickness From bronchial morphometry characterization on computed tomography scan Week 48
Secondary Thickness of the sinus mucosa Week 0
Secondary Thickness of the sinus mucosa Week 48
See also
  Status Clinical Trial Phase
Terminated NCT04410523 - Study of Efficacy and Safety of CSJ117 in Patients With Severe Uncontrolled Asthma Phase 2
Completed NCT04624425 - Additional Effects of Segmental Breathing In Asthma N/A
Active, not recruiting NCT03927820 - A Pharmacist-Led Intervention to Increase Inhaler Access and Reduce Hospital Readmissions (PILLAR) N/A
Completed NCT04617015 - Defining and Treating Depression-related Asthma Early Phase 1
Recruiting NCT03694158 - Investigating Dupilumab's Effect in Asthma by Genotype Phase 4
Terminated NCT04946318 - Study of Safety of CSJ117 in Participants With Moderate to Severe Uncontrolled Asthma Phase 2
Completed NCT04450108 - Vivatmo Pro™ for Fractional Exhaled Nitric Oxide (FeNO) Monitoring in U.S. Asthmatic Patients N/A
Completed NCT03086460 - A Dose Ranging Study With CHF 1531 in Subjects With Asthma (FLASH) Phase 2
Completed NCT01160224 - Oral GW766944 (Oral CCR3 Antagonist) Phase 2
Completed NCT03186209 - Efficacy and Safety Study of Benralizumab in Patients With Uncontrolled Asthma on Medium to High Dose Inhaled Corticosteroid Plus LABA (MIRACLE) Phase 3
Completed NCT02502734 - Effect of Inhaled Fluticasone Furoate on Short-term Growth in Paediatric Subjects With Asthma Phase 3
Completed NCT01715844 - L-Citrulline Supplementation Pilot Study for Overweight Late Onset Asthmatics Phase 1
Terminated NCT04993443 - First-In-Human Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacokinetics of LQ036 Phase 1
Completed NCT02787863 - Clinical and Immunological Efficiency of Bacterial Vaccines at Adult Patients With Bronchopulmonary Pathology Phase 4
Recruiting NCT06033833 - Long-term Safety and Efficacy Evaluation of Subcutaneous Amlitelimab in Adult Participants With Moderate-to-severe Asthma Who Completed Treatment Period of Previous Amlitelimab Asthma Clinical Study Phase 2
Completed NCT03257995 - Pharmacodynamics, Safety, Tolerability, and Pharmacokinetics of Two Orally Inhaled Indacaterol Salts in Adult Subjects With Asthma. Phase 2
Completed NCT02212483 - Clinical Effectiveness and Economical Impact of Medical Indoor Environment Counselors Visiting Homes of Asthma Patients N/A
Recruiting NCT04872309 - MUlti-nuclear MR Imaging Investigation of Respiratory Disease-associated CHanges in Lung Physiology
Withdrawn NCT01468805 - Childhood Asthma Reduction Study N/A
Recruiting NCT05145894 - Differentiation of Asthma/COPD Exacerbation and Stable State Using Automated Lung Sound Analysis With LungPass Device