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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
Participants will receive benralizumab subcutaneously.
Research Site
Walnut Creek, California, United States
Research Site
Change From Baseline in Untrimmed Total Mucus Volume at TLC
Change from baseline in airway dynamics after 13 weeks following treatment with benralizumab, using total mucus volume (specific airway volume) at total lung capacity (TLC) measurements from untrimmed airways was assessed.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC
Change from baseline in untrimmed total mucus plugs score at TLC was assessed. Mucus plugs was scored with a scoring system similar to that by Dunican et al. with the Severe Asthma Research Program (SARP) based on bronchopulmonary segmental anatomy. The mucus score was calculated by counting the number of bronchopulmonary segments which contained 1 or more mucus plug, up to a maximum score of 18 corresponding to the 18 bronchopulmonary segments present in most people. In this system, a mucus plug is defined as a complete occlusion of the airway visible at TLC. Each bronchopulmonary segment is given a score of 1 (mucus plug\[s\] present) or 0 (mucus plug\[s\] absent). The segment scores of each lobe are summed to generate a total mucus score for both lungs, yielding a mucus score ranging from 0-18. Higher scores indicate worse outcome.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Air Trapping at FRC
Change from baseline in untrimmed total air trapping at FRC was assessed.
Time frame: Baseline and Week 13
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC
Change from baseline in trimmed distal airway wall volume at TLC was assessed. Change from baseline in airway dynamics at Week 13 following treatment with benralizumab as measured by secondary FRI endpoints, irrespective of participants characteristics was assessed.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Distal Airway Volume at TLC
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Loxahatchee Groves, Florida, United States
Research Site
Plantation, Florida, United States
Research Site
Greenwood, Indiana, United States
Research Site
Lexington, Kentucky, United States
Research Site
St Louis, Missouri, United States
Research Site
DuBois, Pennsylvania, United States
Research Site
Tyler, Texas, United States
Research Site
Webster, Texas, United States
Research Site
Charlottesville, Virginia, United States
...and 15 more locations
Change from baseline in untrimmed distal airway volume at TLC was assessed.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Distal Airway Volume at Functional Residual Capacity (FRC)
Change from baseline in untrimmed distal airway volume at FRC was assessed.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Lung Volume at TLC
Change from baseline in untrimmed total lung volume at TLC was assessed.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Lung Volume at FRC
Change from baseline in untrimmed total lung volume at FRC was assessed.
Time frame: Baseline and Week 13
Correlation Between Untrimmed Total Mucus Volume Measured at TLC and Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1)
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% confidence interval (CI) for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Mucus Plugs Score at TLC and Pre-BD FEV1
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Air Trapping at FRC and Pre-BD FEV1
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Trimmed Distal Airway Wall Volume at TLC and Pre-BD FEV1
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Distal Airway Volume at TLC and Pre-BD FEV1
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Distal Airway Volume at FRC and Pre-BD FEV1
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Lung Volume at TLC and Pre-BD FEV1
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Lung Volume at FRC and Pre-BD FEV1
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Mucus Volume Measured at TLC and Pre-bronchodilator Forced Vital Capacity (Pre-BD FVC)
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Mucus Plugs Score at TLC and Pre-BD FVC
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Air Trapping at FRC and Pre-BD FVC
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Trimmed Distal Airway Wall Volume at TLC and Pre-BD FVC
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Distal Airway Volume at TLC and Pre-BD FVC
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Distal Airway Volume at FRC and Pre-BD FVC
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Lung Volume at TLC and Pre-BD FVC
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Correlation Between Untrimmed Total Lung Volume at FRC and Pre-BD FVC
The relationship between airway dynamics and conventional lung function measurements, cross sectionally (at week 0) and irrespective of participants characteristics was assessed. Positive correlations were identified by values greater than 0, and negative correlations were identified by values less than 0. Statistical significance is indicated when the lower limit of the 95% CI for the correlation is greater than 0 for positive correlations or less than 0 for negative correlations. Here, "Number" in measure type is indicating data of Spearman's rank correlation coefficient.
Time frame: At Baseline (Week 0)
Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FEV1
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FEV1).
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FEV1
Relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FEV1). Mucus plugs was scored with a scoring system similar to that by Dunican et al. with SARP based on bronchopulmonary segmental anatomy. Mucus score was calculated by counting number of bronchopulmonary segments which contained 1 or more mucus plug, up to a maximum score of 18 corresponding to the 18 bronchopulmonary segments present in most people. In this system, a mucus plug is defined as a complete occlusion of airway visible at TLC. Each bronchopulmonary segment is given a score of 1 (mucus plug present) or 0 (mucus plug absent). The segment scores of each lobe are summed to generate a total mucus score for both lungs, yielding a mucus score ranging from 0-18. Higher scores = worse outcome.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FEV1
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FEV1).
Time frame: Baseline and Week 13
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FEV1
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FEV1).
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FEV1
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FEV1).
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FEV1
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FEV1).
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FVC
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FVC).
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FVC
Relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FVC). Mucus plugs was scored with a scoring system similar to that by Dunican et al. with SARP based on bronchopulmonary segmental anatomy. Mucus score was calculated by counting number of bronchopulmonary segments which contained 1 or more mucus plug, up to a maximum score of 18 corresponding to the 18 bronchopulmonary segments present in most people. In this system, a mucus plug is defined as a complete occlusion of airway visible at TLC. Each bronchopulmonary segment is given a score of 1 (mucus plug present) or 0 (mucus plug absent). The segment scores of each lobe are summed to generate a total mucus score for both lungs, yielding a mucus score ranging from 0-18. Higher scores = worse outcome.
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FVC
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at Week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FVC).
Time frame: Baseline and Week 13
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FVC
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FVC).
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FVC
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FVC).
Time frame: Baseline and Week 13
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FVC
The relationship between changes from baseline (week 0) in airway dynamics and conventional lung function measurements at week 13, after accounting for baseline measurements of conventional lung function was assessed with and without adjustment for conventional lung function measures (pre-BD FVC).
Time frame: Baseline and Week 13
Number of Participants With Adverse Events (AEs)
The safety and tolerability of benralizumab was assessed.
Time frame: From screening (Day -21) to follow-up (up to 1.9 years)