Trial Outcomes & Findings for BURAN: Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging (NCT NCT05552508)

NCT ID: NCT05552508

Last Updated: 2025-03-25

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 45 participants
• Primary outcome timeframe: Baseline and Week 13
• Results posted on: 2025-03-25

Participant Flow

This study was conducted between 11 October 2022 to 19 July 2024 at 24 study centers in in Australia, Belgium, France, Portugal, Spain, United Kingdom, and United States.

Participants who met the inclusion criteria and none of the exclusion criteria were enrolled to the study. Informed Consent Form (ICF) was signed prior of screening procedures. All study assessments were performed as per the Schedule of Activities.

Participant milestones

Measure	Benralizumab Participants received 3 doses of benralizumab 30 milligrams (mg) as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Overall Study STARTED	45
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Benralizumab Participants received 3 doses of benralizumab 30 milligrams (mg) as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Overall Study Adverse Event	3

Baseline Characteristics

BURAN: Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma Using Functional Respiratory Imaging

Baseline characteristics by cohort

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Age, Continuous	54.5 Years STANDARD_DEVIATION 11.4 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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.

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Mucus Volume at TLC Participants with <4 mucus plugs	-0.0056 Milliliters (mL) Standard Deviation 0.0111
Change From Baseline in Untrimmed Total Mucus Volume at TLC All participants	-0.1279 Milliliters (mL) Standard Deviation 0.4199
Change From Baseline in Untrimmed Total Mucus Volume at TLC Participants with >=4 mucus plugs	-0.1822 Milliliters (mL) Standard Deviation 0.4977
Change From Baseline in Untrimmed Total Mucus Volume at TLC OCS-dependent participants	-0.1619 Milliliters (mL) Standard Deviation 0.4627
Change From Baseline in Untrimmed Total Mucus Volume at TLC Non-OCS-dependent participants	-0.1260 Milliliters (mL) Standard Deviation 0.4244

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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.

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC	-11.0 Scores on a scale Standard Deviation 32.8

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Change from baseline in untrimmed total air trapping at FRC was assessed.

Outcome measures

Measure	Benralizumab n=34 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Air Trapping at FRC	-0.1410 Percentage of air trapping Standard Deviation 12.1660

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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.

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC	-0.9386 mL Standard Deviation 6.1359

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

Change from baseline in untrimmed distal airway volume at TLC was assessed.

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Distal Airway Volume at TLC	1.1225 mL Standard Deviation 4.5836

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Change from baseline in untrimmed distal airway volume at FRC was assessed.

Outcome measures

Measure	Benralizumab n=34 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Distal Airway Volume at Functional Residual Capacity (FRC)	0.5079 mL Standard Deviation 1.9741

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

Change from baseline in untrimmed total lung volume at TLC was assessed.

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Lung Volume at TLC	0.0287 Liters (L) Standard Deviation 0.4416

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

Change from baseline in untrimmed total lung volume at FRC was assessed.

Outcome measures

Measure	Benralizumab n=34 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Lung Volume at FRC	-0.0275 Liters (L) Standard Deviation 0.5101

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Mucus Volume Measured at TLC and Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1)	-0.2710 Correlation coefficient Interval -0.526 to 0.0352

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Mucus Plugs Score at TLC and Pre-BD FEV1	-0.2795 Correlation coefficient Interval -0.5326 to 0.026

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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.

Outcome measures

Measure	Benralizumab n=40 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Air Trapping at FRC and Pre-BD FEV1	-0.6892 Correlation coefficient Interval -0.821 to -0.4742

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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.

Outcome measures

Measure	Benralizumab n=42 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Trimmed Distal Airway Wall Volume at TLC and Pre-BD FEV1	0.5380 Correlation coefficient Interval 0.2738 to 0.7205

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Distal Airway Volume at TLC and Pre-BD FEV1	0.6556 Correlation coefficient Interval 0.436 to 0.7958

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Distal Airway Volume at FRC and Pre-BD FEV1	0.4357 Correlation coefficient Interval 0.1383 to 0.6548

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Lung Volume at TLC and Pre-BD FEV1	0.2122 Correlation coefficient Interval -0.0966 to 0.4799

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Lung Volume at FRC and Pre-BD FEV1	-0.1655 Correlation coefficient Interval -0.4519 to 0.156

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Mucus Volume Measured at TLC and Pre-bronchodilator Forced Vital Capacity (Pre-BD FVC)	-0.0471 Correlation coefficient Interval -0.3421 to 0.2574

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Mucus Plugs Score at TLC and Pre-BD FVC	-0.0273 Correlation coefficient Interval -0.3247 to 0.2756

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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.

Outcome measures

Measure	Benralizumab n=40 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Air Trapping at FRC and Pre-BD FVC	-0.3432 Correlation coefficient Interval -0.5886 to -0.0311

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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.

Outcome measures

Measure	Benralizumab n=42 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Trimmed Distal Airway Wall Volume at TLC and Pre-BD FVC	0.5476 Correlation coefficient Interval 0.2863 to 0.7269

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Distal Airway Volume at TLC and Pre-BD FVC	0.6110 Correlation coefficient Interval 0.3742 to 0.767

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=40 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Distal Airway Volume at FRC and Pre-BD FVC	0.4706 Correlation coefficient Interval 0.1806 to 0.6789

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=43 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Lung Volume at TLC and Pre-BD FVC	0.4947 Correlation coefficient Interval 0.2227 to 0.6891

SECONDARY outcome

Timeframe: At Baseline (Week 0)

Population: Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

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.

Outcome measures

Measure	Benralizumab n=40 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Correlation Between Untrimmed Total Lung Volume at FRC and Pre-BD FVC	0.1451 Correlation coefficient Interval -0.1761 to 0.4354

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FEV1 No adjustment for pre-BD FEV1	0.05 mL Interval 0.0 to 0.11
Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FEV1 Adjusted for pre-BD FEV1	0.06 mL Interval 0.0 to 0.12

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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.

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FEV1 No adjustment for pre-BD FEV1	4.38 Scores on a scale Interval -2.87 to 11.63
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FEV1 Adjusted for pre-BD FEV1	5.97 Scores on a scale Interval -1.75 to 13.69

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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).

Outcome measures

Measure	Benralizumab n=34 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FEV1 No adjustment for pre-BD FEV1	3.18 Percentage of air trapping Interval -3.65 to 10.01
Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FEV1 Adjusted for pre-BD FEV1	5.24 Percentage of air trapping Interval -1.23 to 11.71

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FEV1 No adjustment for pre-BD FEV1	5.29 mL Interval -1.39 to 11.97
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FEV1 Adjusted for pre-BD FEV1	5.61 mL Interval -1.27 to 12.48

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed distal airway volume at TLC: No adjustment for pre-BD FEV1	2.20 mL Interval -1.09 to 5.49
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed distal airway volume at TLC: Adjusted for pre-BD FEV1	0.61 mL Interval -2.65 to 3.88
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed distal airway volume at FRC: No adjustment for pre-BD FEV1	-1.28 mL Interval -2.82 to 0.27
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed distal airway volume at FRC: Adjusted for pre-BD FEV1	-1.52 mL Interval -3.14 to 0.09

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed total lung volume at TLC: No adjustment for pre-BD FEV1	0.11 Litre Interval -0.62 to 0.84
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed total lung volume at TLC: Adjusted for pre-BD FEV1	0.13 Litre Interval -0.61 to 0.88
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed total lung volume at FRC: No adjustment for pre-BD FEV1	0.52 Litre Interval -0.16 to 1.21
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FEV1 Untrimmed total lung volume at FRC: Adjusted for pre-BD FEV1	0.37 Litre Interval -0.25 to 0.99

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FVC No adjustment for pre-BD FVC	0.05 mL Interval 0.0 to 0.11
Change From Baseline in Untrimmed Total Mucus Volume Measured at TLC With and Without Adjustment for Pre-BD FVC Adjusted for pre-BD FVC	0.05 mL Interval -0.01 to 0.11

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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.

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FVC No adjustment for pre-BD FVC	4.38 Scores on a scale Interval -2.87 to 11.63
Change From Baseline in Untrimmed Total Mucus Plugs Score at TLC With and Without Adjustment for Pre-BD FVC Adjusted for pre-BD FVC	4.65 Scores on a scale Interval -3.0 to 12.3

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number of participants analyzed' specifies all participants who were evaluated for this outcome measure.

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).

Outcome measures

Measure	Benralizumab n=34 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FVC No adjustment for pre-BD FVC	3.18 Percentage of air trapping Interval -3.65 to 10.01
Change From Baseline in Untrimmed Total Air Trapping at FRC With and Without Adjustment for Pre-BD FVC Adjusted for pre-BD FVC	4.36 Percentage of air trapping Interval -2.06 to 10.79

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FVC Adjusted for pre-BD FVC	6.08 mL Interval -0.6 to 12.76
Change From Baseline in Trimmed Distal Airway Wall Volume at TLC With and Without Adjustment for Pre-BD FVC No adjustment for pre-BD FVC	5.29 mL Interval -1.39 to 11.97

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FVC Untrimmed distal airway volume at TLC: No adjustment for pre-BD FVC	2.20 mL Interval -1.09 to 5.49
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FVC Untrimmed distal airway volume at TLC: Adjusted for pre-BD FVC	1.22 mL Interval -2.3 to 4.73
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FVC Untrimmed distal airway volume at FRC: No adjustment for pre-BD FVC	-1.28 mL Interval -2.82 to 0.27
Change From Baseline in Untrimmed Distal Airway Volume With and Without Adjustment for Pre-BD FVC Untrimmed distal airway volume at FRC: Adjusted for pre-BD FVC	-1.28 mL Interval -2.93 to 0.37

SECONDARY outcome

Timeframe: Baseline and Week 13

Population: Primary analysis population set consisted portion of the evaluable population that did not have any acute asthma exacerbation nor lower respiratory tract infection during the study period. Here, 'number analyzed in each row' signifies the participants with available data that were analyzed for specified category.

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).

Outcome measures

Measure	Benralizumab n=39 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FVC Untrimmed total lung volume at TLC: No adjustment for pre-BD FVC	0.11 Litre Interval -0.62 to 0.84
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FVC Untrimmed total lung volume at TLC: Adjusted for pre-BD FVC	0.11 Litre Interval -0.63 to 0.85
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FVC Untrimmed total lung volume at FRC: No adjustment for pre-BD FVC	0.52 Litre Interval -0.16 to 1.21
Change From Baseline in Untrimmed Total Lung Volume With and Without Adjustment for Pre-BD FVC Untrimmed total lung volume at FRC: Adjusted for pre-BD FVC	0.40 Litre Interval -0.22 to 1.02

SECONDARY outcome

Timeframe: From screening (Day -21) to follow-up (up to 1.9 years)

Population: The safety analysis set consisted of all participants who had received at least one dose of study intervention.

The safety and tolerability of benralizumab was assessed.

Outcome measures

Measure	Benralizumab n=45 Participants Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Number of Participants With Adverse Events (AEs) Any AE	17 Participants
Number of Participants With Adverse Events (AEs) Any serious adverse event (SAE)	2 Participants
Number of Participants With Adverse Events (AEs) Any SAE with outcome death	0 Participants
Number of Participants With Adverse Events (AEs) Any AE leading to discontinuation of study intervention	1 Participants
Number of Participants With Adverse Events (AEs) Any possibly related AE	3 Participants

Adverse Events

Benralizumab

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Benralizumab n=45 participants at risk Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Infections and infestations Respiratory tract infection	2.2% 1/45 • Number of events 1 • From screening (Day -21) to follow-up (up to 1.9 years) The Safety analysis set consisted of all participants who had received at least one dose of investigational product.
Respiratory, thoracic and mediastinal disorders Asthma	2.2% 1/45 • Number of events 1 • From screening (Day -21) to follow-up (up to 1.9 years) The Safety analysis set consisted of all participants who had received at least one dose of investigational product.

Other adverse events

Measure	Benralizumab n=45 participants at risk Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).
Infections and infestations Gastroenteritis	6.7% 3/45 • Number of events 4 • From screening (Day -21) to follow-up (up to 1.9 years) The Safety analysis set consisted of all participants who had received at least one dose of investigational product.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB.
• Publication restrictions are in place

Restriction type: OTHER