Back to resultsBURAN: Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging (BURAN)
Primary Purpose
Asthma
Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Benralizumab
Sponsored by
About this trial
This is an interventional treatment trial for Asthma focused on measuring BURAN, Inhaled Corticosteroids, Long-acting β2 agonists, Benralizumab, Eosinophilic Asthma
Eligibility Criteria
Inclusion Criteria:
- Participants who are diagnosed with asthma with documented reversibility post-bronchodilator or salbutamol either historical or at Visit 0 (V0).
- Participants who have documented treatment with ICS and LABA for ≥ 3 months prior to V0 with or without oral corticosteroids and additional asthma controllers.
- Participants who have documented peripheral blood eosinophil count ≥ 300 cells/μL at V0, or if Oral Corticosteroids (OCS)-dependent, a documented peripheral blood eosinophil count ≥ 150 cells/μL at V0.
- Participants who have had a minimum of 2 exacerbations in the last 12 months prior to V0.
- Participants who have pre-bronchodilator Forced Vital Capacity (FVC) < 65% of predicted at V0.
- Participants who have pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% of predicted at V0.
- Participants who have stable asthma regimen apart from the use of rescue medication including the use of any other asthma medication for at least 3 months prior to V0.
- Participants who can perform acceptable and repeatable spirometry.
- Participants who can withhold asthma maintenance medication for at least 12 hours prior to V0, 1 and 4 where spirometry and/or Computed Tomography (CT) scan procedures will be performed except for once-a-day dosage where 24 hours will be required.
- Female participants who have a negative pregnancy test prior to administration of the investigational product (IP) and high-resolution CT scan and must agree to use a highly effective method of birth control from randomization throughout the study duration and within 12 weeks after last dose of IP.
Exclusion Criteria:
- Participants who are unstable or who experienced an exacerbation/infection in the 6 weeks before V0.
- Participants with acute upper or lower airway infection in the 6 weeks before V0.
- Participants diagnosed with clinically important pulmonary disease other than asthma, or participants who have ever been diagnosed with pulmonary or systemic disease, other than asthma that are associated with elevated peripheral eosinophil count.
- Receipt of any biologic products for asthma within 4 months or 5 half-lives prior to V0 whichever is longer.
- History or current use of chronic (i.e., > 4 weeks) immunosuppressive medication.
- History of lung volume reduction surgery, lung resection, thermal bronchoplasty at any time before visit 0 (V0) or on active phase of pulmonary rehabilitation.
- Participants with current malignancy or history of malignancy.
- History of other clinically significant disease or abnormality.
- Participants with positive Hepatitis B, C or HIV.
- Participants with:
Positive COVID-19 test at V0, COVID-19 disease within 6 weeks before V0 or History of severe COVID-19 disease at any time, defined by the need for Intensive Care Unit stay or Mechanical Ventilation (invasive or non-invasive).
Sites / Locations
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Benralizumab
Arm Description
Participants will receive 3 doses of benralizumab having a strength of 30 mg subcutaneously once every 4 weeks (Week 0, Week 4, and Week 8).
Outcomes
Primary Outcome Measures
Change from baseline in specific airway volume (siVaw)
The change from baseline to Week 13 in siVaw of trimmed airways measured using quantitative CT analysis following treatment with benralizumab calculated as the mean percent change from baseline will be assessed.
Secondary Outcome Measures
Change from baseline in Lung volume (iVlung)
The change from baseline to Week 13 in iVlung measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Change from baseline in Lobar volume (iVlobe)
The change from baseline to Week 13 in iVlobe measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Change from baseline in Airway volume (iVaww)
The change from baseline to Week 13 in iVaw measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Change from baseline in air trapping
The change from baseline to Week 13 in air trapping measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Change from baseline in Airway resistance (iRaw)
The change from baseline to Week 13 in airway resistance measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Change from baseline in mucus plugs score
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by mucus plugs scores will be assessed. High baseline mucus scores have shown to have significant improvements in Ventilation Defect Percent (VDP) and asthma control post-benralizumab while those with low mucus scores have not.
The scale has an upper bound of 20. An increase in Mucus Plug Score implies an increase in the number of observed obstructive mucus plugs and is understood to represent a worse outcome. A decrease represents a decrease in the number of observed obstructive mucus plugs and is understood to represent a better outcome. Mucus plugs will be scored with a scoring system based on bronchopulmonary segmental anatomy. Each bronchopulmonary segment will be given a score of 1 (mucus plug present) or 0 (mucus plug absent).
Change from baseline in Blood Vessel measurements (BVX) measured in millilitres (mL)
BV5 - The change from baseline to Week 13 of BV5, the volume in milliliters of intrapulmonary vessel-like markings >= 5 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed.
BV5-10 - The change from baseline to Week 13 of BV5-10, the volume in milliliters of intrapulmonary vessel-like markings >5 mm2 and < 10 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed.
BV10 - The change from baseline to Week 13 of BV10, the volume in milliliters of intrapulmonary vessel-like markings >=10 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed
TBV - The change from baseline to Week 13 of TBV, the volume in milliliters of all intrapulmonary vessel-like markings as measured by quantitative CT analysis will be assessed.
Percent change from baseline in BVX
BV5/TBV - The change from baseline to Week 13 of BV5/TBV, BV5 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV5/TBV)x100 will be assessed.
BV5-10/TBV - The change from baseline to Week 13 of BV5-10/TBV, BV5-10 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV5-10/TBV)x100 will be assessed.
BV10/TBV - The change from baseline to Week 13 of BV10/TBV, BV10 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV10/TBV)x100 will be assessed.
Change from baseline in Internal Airflow Distribution (IAD)
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by IAD will be assessed.
Change from baseline in CT-based imaging ventilation heterogeneity, defined as the standard deviation of the histogram of voxel-wise deformation representing the local expansion of lung tissue during inspiration, measured by quantitative CT analysis
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by ventilation mapping will be assessed.
Change from baseline in ventilation/perfusion mapping
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by ventilation/perfusion mapping will be assessed. Ventilation/perfusion is an arithmetic manipulation of other outcome measures which results in a unitless number, and is arrived at for a given lobe by dividing the difference in lobar volume (iVlobe) between inspiratory (TLC) and expiratory (FRC) scans by the TBV for that lobe.
Correlation between imaging endpoints (FRI endpoints and mucus plugs score) and pre-bronchodilator forced expiratory volume (pre-BD FEV1)
The relationship between imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FEV1 will be assessed.
Correlation between imaging endpoints (FRI endpoints and mucus plugs score) and pre-bronchodilator forced vital capacity (pre-BD FVC)
The relationship between imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FVC will be assessed.
Correlation between the change in imaging endpoints (FRI endpoints and mucus plugs score) and the change in pre-BD FEV1 (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FEV1
The relationship between change from baseline to Week 13 in imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FEV1 will be assessed.
Correlation between the change in imaging endpoints (FRI endpoints and mucus plugs score) and the change in pre-BD FVC (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FVC
The relationship between change from baseline to Week 13 in imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FVC will be assessed.
Number of patients with Adverse Events (AEs)
The safety and tolerability of benralizumab will be assessed.
Change from baseline in siVaw with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in siVaw measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in siVaw with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in siVaw measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in iVlung with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in iVlung measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in iVlung with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in iVlung measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in iVlobe with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in iVlobe measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in iVlobe with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in iVlobe measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in iVaww with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in iVaww measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in iVaww with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in iVaww measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in air trapping with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in air trapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in air trapping with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in air trapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in iRaw with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in iRaw measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in iRaw with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in iRaw measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in BVX with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in BVX measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in BVX with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in BVX measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in IAD with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in IAD measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in IAD with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in IAD measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in ventilation mapping with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in ventilation mapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in ventilation mapping with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in ventilation mapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in ventilation/perfusion mapping with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in ventilation/perfusion mapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in ventilation/perfusion mapping with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in ventilation/perfusion mapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in mucus plugs score with and without adjustment for pre-BD FEV1
The relationship between change from baseline to Week 13 in mucus plugs score measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Change from baseline in mucus plugs score with and without adjustment for pre-BD FVC
The relationship between change from baseline to Week 13 in mucus plugs score measured using quantitative CT analysis and pre-BD FVC will be assessed.
Change from baseline in imaging endpoints (FRI endpoints and mucus plugs score) for every one percent correlation between pre-BD FEV1 and pre-BD FVC
The change from baseline to Week 13 in the estimated average change in each imaging endpoint (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) for every one percent increase in pre-BD FEV1 and pre-BD FVC will be assessed.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05552508
Brief Title
BURAN: Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging
Acronym
BURAN
Official Title
BURAN: Effects of Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging Parameters
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 11, 2022 (Actual)
Primary Completion Date
April 5, 2024 (Anticipated)
Study Completion Date
April 5, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will assess the effects of benralizumab on airway dynamics in severe eosinophilic asthma in terms of quantitative computed tomography (CT)-derived measurements of pulmonary structure and function using the Functional Respiratory Imaging (FRI) platform.
Detailed Description
This is a phase IV, interventional single group, open-label, uncontrolled, prospective, multicenter clinical trial.
This study will be conducted in male and female participants ≥18 years old with established severe eosinophilic asthma as defined by European Respiratory Society (ERS)/American Thoracic Society (ATS) clinical guidelines inadequately controlled by treatment with Inhaled Corticosteroids-Long-acting β2 agonists (ICS-LABA) with or without oral corticosteroids (OCS) or other asthma controller medications.
Each participant will participate in the study for a minimum of 15 weeks and up to 23 weeks.
This study will comprise of:
Screening visit (V0) Visit 1 (V1; week 0; within 1 to 21 days of screening) Visit 2 (V2; week 4 ± 5 days) Visit 3 (V3; week 8 ± 5 days) Visit 4 (V4; week 13 ± 5 days) Follow-up (2 weeks [± 7 days] after V4) - Phone call follow-up. Participants will be discharged from the study after the phone call follow-up is completed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma
Keywords
BURAN, Inhaled Corticosteroids, Long-acting β2 agonists, Benralizumab, Eosinophilic Asthma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
138 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Benralizumab
Arm Type
Experimental
Arm Description
Participants will receive 3 doses of benralizumab having a strength of 30 mg subcutaneously once every 4 weeks (Week 0, Week 4, and Week 8).
Intervention Type
Combination Product
Intervention Name(s)
Benralizumab
Other Intervention Name(s)
Fasenra
Intervention Description
Participants will receive benralizumab subcutaneously.
Primary Outcome Measure Information:
Title
Change from baseline in specific airway volume (siVaw)
Description
The change from baseline to Week 13 in siVaw of trimmed airways measured using quantitative CT analysis following treatment with benralizumab calculated as the mean percent change from baseline will be assessed.
Time Frame
Baseline (at week 0), Week 13
Secondary Outcome Measure Information:
Title
Change from baseline in Lung volume (iVlung)
Description
The change from baseline to Week 13 in iVlung measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in Lobar volume (iVlobe)
Description
The change from baseline to Week 13 in iVlobe measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in Airway volume (iVaww)
Description
The change from baseline to Week 13 in iVaw measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in air trapping
Description
The change from baseline to Week 13 in air trapping measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in Airway resistance (iRaw)
Description
The change from baseline to Week 13 in airway resistance measured using quantitative CT analysis following treatment with benralizumab will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in mucus plugs score
Description
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by mucus plugs scores will be assessed. High baseline mucus scores have shown to have significant improvements in Ventilation Defect Percent (VDP) and asthma control post-benralizumab while those with low mucus scores have not.
The scale has an upper bound of 20. An increase in Mucus Plug Score implies an increase in the number of observed obstructive mucus plugs and is understood to represent a worse outcome. A decrease represents a decrease in the number of observed obstructive mucus plugs and is understood to represent a better outcome. Mucus plugs will be scored with a scoring system based on bronchopulmonary segmental anatomy. Each bronchopulmonary segment will be given a score of 1 (mucus plug present) or 0 (mucus plug absent).
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in Blood Vessel measurements (BVX) measured in millilitres (mL)
Description
BV5 - The change from baseline to Week 13 of BV5, the volume in milliliters of intrapulmonary vessel-like markings >= 5 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed.
BV5-10 - The change from baseline to Week 13 of BV5-10, the volume in milliliters of intrapulmonary vessel-like markings >5 mm2 and < 10 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed.
BV10 - The change from baseline to Week 13 of BV10, the volume in milliliters of intrapulmonary vessel-like markings >=10 mm2 in cross sectional area as measured by quantitative CT analysis will be assessed
TBV - The change from baseline to Week 13 of TBV, the volume in milliliters of all intrapulmonary vessel-like markings as measured by quantitative CT analysis will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Percent change from baseline in BVX
Description
BV5/TBV - The change from baseline to Week 13 of BV5/TBV, BV5 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV5/TBV)x100 will be assessed.
BV5-10/TBV - The change from baseline to Week 13 of BV5-10/TBV, BV5-10 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV5-10/TBV)x100 will be assessed.
BV10/TBV - The change from baseline to Week 13 of BV10/TBV, BV10 as percent of Total Pulmonary Blood Volume (TBV), computed as (BV10/TBV)x100 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in Internal Airflow Distribution (IAD)
Description
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by IAD will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in CT-based imaging ventilation heterogeneity, defined as the standard deviation of the histogram of voxel-wise deformation representing the local expansion of lung tissue during inspiration, measured by quantitative CT analysis
Description
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by ventilation mapping will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in ventilation/perfusion mapping
Description
The change from baseline to Week 13 in airway dynamics following treatment with benralizumab as measured by ventilation/perfusion mapping will be assessed. Ventilation/perfusion is an arithmetic manipulation of other outcome measures which results in a unitless number, and is arrived at for a given lobe by dividing the difference in lobar volume (iVlobe) between inspiratory (TLC) and expiratory (FRC) scans by the TBV for that lobe.
Time Frame
Baseline (at week 0), Week 13
Title
Correlation between imaging endpoints (FRI endpoints and mucus plugs score) and pre-bronchodilator forced expiratory volume (pre-BD FEV1)
Description
The relationship between imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0)
Title
Correlation between imaging endpoints (FRI endpoints and mucus plugs score) and pre-bronchodilator forced vital capacity (pre-BD FVC)
Description
The relationship between imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0)
Title
Correlation between the change in imaging endpoints (FRI endpoints and mucus plugs score) and the change in pre-BD FEV1 (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Correlation between the change in imaging endpoints (FRI endpoints and mucus plugs score) and the change in pre-BD FVC (± 5 days), overall and within subgroups conditional on the baseline value of pre-BD FVC
Description
The relationship between change from baseline to Week 13 in imaging endpoints (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Number of patients with Adverse Events (AEs)
Description
The safety and tolerability of benralizumab will be assessed.
Time Frame
From screening to follow-up (up to 1.4 years)
Title
Change from baseline in siVaw with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in siVaw measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in siVaw with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in siVaw measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iVlung with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in iVlung measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iVlung with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in iVlung measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iVlobe with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in iVlobe measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iVlobe with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in iVlobe measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iVaww with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in iVaww measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iVaww with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in iVaww measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in air trapping with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in air trapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in air trapping with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in air trapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iRaw with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in iRaw measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in iRaw with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in iRaw measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in BVX with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in BVX measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in BVX with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in BVX measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in IAD with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in IAD measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in IAD with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in IAD measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in ventilation mapping with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in ventilation mapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in ventilation mapping with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in ventilation mapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in ventilation/perfusion mapping with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in ventilation/perfusion mapping measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in ventilation/perfusion mapping with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in ventilation/perfusion mapping measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in mucus plugs score with and without adjustment for pre-BD FEV1
Description
The relationship between change from baseline to Week 13 in mucus plugs score measured using quantitative CT analysis and pre-BD FEV1 will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in mucus plugs score with and without adjustment for pre-BD FVC
Description
The relationship between change from baseline to Week 13 in mucus plugs score measured using quantitative CT analysis and pre-BD FVC will be assessed.
Time Frame
Baseline (at week 0), Week 13
Title
Change from baseline in imaging endpoints (FRI endpoints and mucus plugs score) for every one percent correlation between pre-BD FEV1 and pre-BD FVC
Description
The change from baseline to Week 13 in the estimated average change in each imaging endpoint (siVaw, iVlung, iVlobe, iVaww, air trapping, iRaw, BVX, IAD, ventilation mapping, ventilation/perfusion mapping and mucus plugs score) for every one percent increase in pre-BD FEV1 and pre-BD FVC will be assessed.
Time Frame
Week 0, and Week 13
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants who are diagnosed with asthma with documented reversibility post-bronchodilator or salbutamol either historical or at Visit 0 (V0).
Participants who have documented treatment with ICS and LABA for ≥ 3 months prior to V0 with or without oral corticosteroids and additional asthma controllers.
Participants who have documented peripheral blood eosinophil count ≥ 300 cells/μL at V0, or if Oral Corticosteroids (OCS)-dependent, a documented peripheral blood eosinophil count ≥ 150 cells/μL at V0.
Participants who have had a minimum of 2 exacerbations in the last 12 months prior to V0.
Participants who have pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)/Forced Vital Capacity (FVC) ≤ 70% at Visit 0 (V0).
Participants who have pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) < 80% of predicted at V0.
Participants who can perform acceptable and repeatable spirometry.
Participants who can withhold asthma maintenance medication for at least 12 hours prior to V0, 1 and 4 where spirometry and/or Computed Tomography (CT) scan procedures will be performed except for once-a-day dosage where 24 hours will be required.
Female participants who have a negative pregnancy test prior to administration of the investigational product (IP) and high-resolution CT scan and must agree to use a highly effective method of birth control from randomization throughout the study duration and within 12 weeks after last dose of IP.
Exclusion Criteria:
Participants who are unstable or who experienced an exacerbation/infection in the 6 weeks before V0.
Participants with acute upper or lower airway infection in the 6 weeks before V0.
Participants diagnosed with clinically important pulmonary disease other than asthma, or participants who have ever been diagnosed with pulmonary or systemic disease, other than asthma that are associated with elevated peripheral eosinophil count.
Receipt of any biologic products for asthma within 4 months or 5 half-lives prior to V0 whichever is longer.
History or current use of chronic (i.e., > 4 weeks) immunosuppressive medication.
History of lung volume reduction surgery, lung resection, thermal bronchoplasty at any time before visit 0 (V0) or on active phase of pulmonary rehabilitation.
Participants with current malignancy or history of malignancy.
History of other clinically significant disease or abnormality.
Participants with positive Hepatitis B, C or HIV.
Participants with:
Positive COVID-19 test at V0, COVID-19 disease within 6 weeks before V0 or History of severe COVID-19 disease at any time, defined by the need for Intensive Care Unit stay or Mechanical Ventilation (invasive or non-invasive).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Walnut Creek
State/Province
California
ZIP/Postal Code
94598
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80206
Country
United States
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Loxahatchee Groves
State/Province
Florida
ZIP/Postal Code
33470
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Plantation
State/Province
Florida
ZIP/Postal Code
33324
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Greenwood
State/Province
Indiana
ZIP/Postal Code
46143
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40502
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40536
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Withdrawn
Facility Name
Research Site
City
DuBois
State/Province
Pennsylvania
ZIP/Postal Code
15801
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37909
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Tyler
State/Province
Texas
ZIP/Postal Code
75708
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Individual Site Status
Recruiting
Facility Name
Research Site
City
Box Hill
ZIP/Postal Code
3128
Country
Australia
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Clayton
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Recruiting
Facility Name
Research Site
City
Frankston
ZIP/Postal Code
3199
Country
Australia
Individual Site Status
Recruiting
Facility Name
Research Site
City
Toorak Gardens
ZIP/Postal Code
5065
Country
Australia
Individual Site Status
Recruiting
Facility Name
Research Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Research Site
City
Mechelen
ZIP/Postal Code
2800
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Research Site
City
Montigny-le-Tilleul
ZIP/Postal Code
6110
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Research Site
City
Namur
ZIP/Postal Code
5101
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Research Site
City
Roeselare
ZIP/Postal Code
8800
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Research Site
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Caen
ZIP/Postal Code
F-14033
Country
France
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Cannes
ZIP/Postal Code
06414
Country
France
Individual Site Status
Recruiting
Facility Name
Research Site
City
Clermond Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Recruiting
Facility Name
Research Site
City
Libourne Cedex
ZIP/Postal Code
33505
Country
France
Individual Site Status
Recruiting
Facility Name
Research Site
City
Montpellier Cedex 5
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Name
Research Site
City
Lisboa
ZIP/Postal Code
1349-019
Country
Portugal
Individual Site Status
Withdrawn
Facility Name
Research Site
City
Lisboa
ZIP/Postal Code
1649-035
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Research Site
City
Portimão
ZIP/Postal Code
8500-338
Country
Portugal
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Porto
ZIP/Postal Code
4100-180
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Research Site
City
Alzira
ZIP/Postal Code
46410
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08006
Country
Spain
Individual Site Status
Completed
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08017
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
8003
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Madrid
ZIP/Postal Code
28007
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Santander
ZIP/Postal Code
39008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Villarreal (Castellón)
ZIP/Postal Code
12540
Country
Spain
Individual Site Status
Recruiting
Facility Name
Research Site
City
Bradford
ZIP/Postal Code
BND9 6RJ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Research Site
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Research Site
City
St Just
ZIP/Postal Code
TR19 7HX
Country
United Kingdom
Individual Site Status
Withdrawn
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment:
https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Learn more about this trial
BURAN: Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging
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