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

Study identifier:D3250R00107

ClinicalTrials.gov identifier:NCT05552508

EudraCT identifier:2022-000152-11

CTIS identifier:N/A

Study Complete

Official Title

BURAN: Effects of Benralizumab on Airway Dynamics in Severe Eosinophilic Asthma using Functional Respiratory Imaging Parameters

Medical condition

asthma

Phase

Phase 4

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 70 Years

Date

Study Start Date: 11 Oct 2022

Primary Completion Date: 19 Jul 2024

Study Completion Date: 19 Jul 2024

Study design

Allocation: N/A
Endpoint Classification: -
Intervention Model: Single Group Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2025 by AstraZeneca

Collaborators

Inclusion and exclusion 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).

Location

Research Site

Plantation, FL, United States, 33324

Location

Research Site

Greenwood, IN, United States, 46143

Location

Research Site

Barcelona, Spain, 08006

Location

Research Site

Saint Louis, MO, United States, 63110

Location

Research Site

Madrid, Spain, 28007

Location

Research Site

Namur, Belgium, 5101

Location

Research Site

Villarreal (Castellón), Spain, 12540

Location

Research Site

Barcelona, Spain, 8003

Arms	Assigned Interventions
Experimental: Benralizumab 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).	-

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups

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

Participant Flow: Overall Study

	Benralizumab
STARTED	45
COMPLETED	42
NOT COMPLETED	3
Adverse Event	3

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Baseline Measures

	Benralizumab
Number of Participants [units: Participants]	39
Age Continuous [units: Years] Mean ± Standard Deviation	54.5 ± 11.4
Sex: Female, Male [units: Participants]
Female	23
Male	16
Ethnicity (NIH/OMB) [units: Participants]
Hispanic or Latino	6
Not Hispanic or Latino	33
Unknown or Not Reported	0

Outcome Measures

1. Primary Outcome Measure: Change from baseline in untrimmed total mucus volume at TLC [ Time Frame: Baseline and Week 13 ]

Measure Type	Primary
Measure Name	Change from baseline in untrimmed total mucus volume at TLC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total mucus volume at TLC [units: Milliliters (mL)] Mean (Standard Deviation)
All participants	-0.1279 (0.4199)
Participants with >=4 mucus plugs	-0.1822 (0.4977)
Participants with <4 mucus plugs	-0.0056 (0.0111)
OCS-dependent participants	-0.1619 (0.4627)
Non-OCS-dependent participants	-0.1260 (0.4244)

Statistical Analysis 1 for Change from baseline in untrimmed total mucus volume at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.0327

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	All participants
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 2 for Change from baseline in untrimmed total mucus volume at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.0359

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Participants with >=4 mucus plugs
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 3 for Change from baseline in untrimmed total mucus volume at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.1088

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Participants with <4 mucus plugs
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

Statistical Analysis 4 for Change from baseline in untrimmed total mucus volume at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.0391

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Non-OCS-dependent participants
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

2. Secondary Outcome Measure: Change from baseline in untrimmed total mucus plugs score at TLC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total mucus plugs score at TLC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total mucus plugs score at TLC [units: Scores on a scale] Mean (Standard Deviation)	-11.0 (32.8)

Statistical Analysis 1 for Change from baseline in untrimmed total mucus plugs score at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.0423

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

3. Secondary Outcome Measure: Change from baseline in untrimmed total air trapping at FRC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total air trapping at FRC
Measure Description	Change from baseline in untrimmed total air trapping at FRC was assessed.
Time Frame	Baseline and Week 13
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	34
Change from baseline in untrimmed total air trapping at FRC [units: Percentage of air trapping] Mean (Standard Deviation)	-0.1410 (12.1660)

Statistical Analysis 1 for Change from baseline in untrimmed total air trapping at FRC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.9465

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

4. Secondary Outcome Measure: Change from baseline in trimmed distal airway wall volume at TLC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in trimmed distal airway wall volume at TLC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in trimmed distal airway wall volume at TLC [units: mL] Mean (Standard Deviation)	-0.9386 (6.1359)

Statistical Analysis 1 for Change from baseline in trimmed distal airway wall volume at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.3455

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

5. Secondary Outcome Measure: Change from baseline in untrimmed distal airway volume at TLC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed distal airway volume at TLC
Measure Description	Change from baseline in untrimmed distal airway volume at TLC was assessed.
Time Frame	Baseline and Week 13
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed distal airway volume at TLC [units: mL] Mean (Standard Deviation)	1.1225 (4.5836)

Statistical Analysis 1 for Change from baseline in untrimmed distal airway volume at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.2484

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

6. Secondary Outcome Measure: Change from baseline in untrimmed distal airway volume at functional residual capacity (FRC) [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed distal airway volume at functional residual capacity (FRC)
Measure Description	Change from baseline in untrimmed distal airway volume at FRC was assessed.
Time Frame	Baseline and Week 13
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	34
Change from baseline in untrimmed distal airway volume at functional residual capacity (FRC) [units: mL] Mean (Standard Deviation)	0.5079 (1.9741)

Statistical Analysis 1 for Change from baseline in untrimmed distal airway volume at functional residual capacity (FRC)

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.9405

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

7. Secondary Outcome Measure: Change from baseline in untrimmed total lung volume at TLC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total lung volume at TLC
Measure Description	Change from baseline in untrimmed total lung volume at TLC was assessed.
Time Frame	Baseline and Week 13
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total lung volume at TLC [units: Liters (L)] Mean (Standard Deviation)	0.0287 (0.4416)

Statistical Analysis 1 for Change from baseline in untrimmed total lung volume at TLC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.6867

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

8. Secondary Outcome Measure: Change from baseline in untrimmed total lung volume at FRC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total lung volume at FRC
Measure Description	Change from baseline in untrimmed total lung volume at FRC was assessed.
Time Frame	Baseline and Week 13
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	34
Change from baseline in untrimmed total lung volume at FRC [units: Liters (L)] Mean (Standard Deviation)	-0.0275 (0.5101)

Statistical Analysis 1 for Change from baseline in untrimmed total lung volume at FRC

Groups^[1]	All groups
Method^[3]	t-test, 2 sided
P-Value^[4]	0.7554

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.

9. Secondary Outcome Measure: Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1) [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1)
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1) [units: Correlation coefficient] Number (95% Confidence Interval)	-0.2710 (-0.5260 to 0.0352)

No statistical analysis provided for Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced expiratory volume in 1 second (pre-BD FEV1)

10. Secondary Outcome Measure: Correlation between untrimmed total mucus plugs score at TLC and pre-BD FEV1 [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total mucus plugs score at TLC and pre-BD FEV1
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed total mucus plugs score at TLC and pre-BD FEV1 [units: Correlation coefficient] Number (95% Confidence Interval)	-0.2795 (-0.5326 to 0.0260)

No statistical analysis provided for Correlation between untrimmed total mucus plugs score at TLC and pre-BD FEV1

11. Secondary Outcome Measure: Correlation between untrimmed total air trapping at FRC and pre-BD FEV1 [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total air trapping at FRC and pre-BD FEV1
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	40
Correlation between untrimmed total air trapping at FRC and pre-BD FEV1 [units: Correlation coefficient] Number (95% Confidence Interval)	-0.6892 (-0.8210 to -0.4742)

No statistical analysis provided for Correlation between untrimmed total air trapping at FRC and pre-BD FEV1

12. Secondary Outcome Measure: Correlation between trimmed distal airway wall volume at TLC and pre-BD FEV1 [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between trimmed distal airway wall volume at TLC and pre-BD FEV1
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	42
Correlation between trimmed distal airway wall volume at TLC and pre-BD FEV1 [units: Correlation coefficient] Number (95% Confidence Interval)	0.5380 (0.2738 to 0.7205)

No statistical analysis provided for Correlation between trimmed distal airway wall volume at TLC and pre-BD FEV1

13. Secondary Outcome Measure: Correlation between untrimmed distal airway volume at TLC and pre-BD FEV1 [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed distal airway volume at TLC and pre-BD FEV1
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed distal airway volume at TLC and pre-BD FEV1 [units: Correlation coefficient] Number (95% Confidence Interval)	0.6556 (0.4360 to 0.7958)

No statistical analysis provided for Correlation between untrimmed distal airway volume at TLC and pre-BD FEV1

14. Secondary Outcome Measure: Correlation between untrimmed distal airway volume at FRC and pre-BD FEV1 [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed distal airway volume at FRC and pre-BD FEV1
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed distal airway volume at FRC and pre-BD FEV1 [units: Correlation coefficient] Number (95% Confidence Interval)	0.4357 (0.1383 to 0.6548)

No statistical analysis provided for Correlation between untrimmed distal airway volume at FRC and pre-BD FEV1

15. Secondary Outcome Measure: Correlation between untrimmed total lung volume at TLC and pre-BD FEV1 [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total lung volume at TLC and pre-BD FEV1
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed total lung volume at TLC and pre-BD FEV1 [units: Correlation coefficient] Number (95% Confidence Interval)	0.2122 (-0.0966 to 0.4799)

No statistical analysis provided for Correlation between untrimmed total lung volume at TLC and pre-BD FEV1

16. Secondary Outcome Measure: Correlation between untrimmed total lung volume at FRC and pre-BD FEV1 [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total lung volume at FRC and pre-BD FEV1
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed total lung volume at FRC and pre-BD FEV1 [units: Correlation coefficient] Number (95% Confidence Interval)	-0.1655 (-0.4519 to 0.1560)

No statistical analysis provided for Correlation between untrimmed total lung volume at FRC and pre-BD FEV1

17. Secondary Outcome Measure: Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced vital capacity (pre-BD FVC) [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced vital capacity (pre-BD FVC)
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced vital capacity (pre-BD FVC) [units: Correlation coefficient] Number (95% Confidence Interval)	-0.0471 (-0.3421 to 0.2574)

No statistical analysis provided for Correlation between untrimmed total mucus volume measured at TLC and pre-bronchodilator forced vital capacity (pre-BD FVC)

18. Secondary Outcome Measure: Correlation between untrimmed total mucus plugs score at TLC and pre-BD FVC [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total mucus plugs score at TLC and pre-BD FVC
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed total mucus plugs score at TLC and pre-BD FVC [units: Correlation coefficient] Number (95% Confidence Interval)	-0.0273 (-0.3247 to 0.2756)

No statistical analysis provided for Correlation between untrimmed total mucus plugs score at TLC and pre-BD FVC

19. Secondary Outcome Measure: Correlation between untrimmed total air trapping at FRC and pre-BD FVC [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total air trapping at FRC and pre-BD FVC
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	40
Correlation between untrimmed total air trapping at FRC and pre-BD FVC [units: Correlation coefficient] Number (95% Confidence Interval)	-0.3432 (-0.5886 to -0.0311)

No statistical analysis provided for Correlation between untrimmed total air trapping at FRC and pre-BD FVC

20. Secondary Outcome Measure: Correlation between trimmed distal airway wall volume at TLC and pre-BD FVC [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between trimmed distal airway wall volume at TLC and pre-BD FVC
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	42
Correlation between trimmed distal airway wall volume at TLC and pre-BD FVC [units: Correlation coefficient] Number (95% Confidence Interval)	0.5476 (0.2863 to 0.7269)

No statistical analysis provided for Correlation between trimmed distal airway wall volume at TLC and pre-BD FVC

21. Secondary Outcome Measure: Correlation between untrimmed distal airway volume at TLC and pre-BD FVC [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed distal airway volume at TLC and pre-BD FVC
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed distal airway volume at TLC and pre-BD FVC [units: Correlation coefficient] Number (95% Confidence Interval)	0.6110 (0.3742 to 0.7670)

No statistical analysis provided for Correlation between untrimmed distal airway volume at TLC and pre-BD FVC

22. Secondary Outcome Measure: Correlation between untrimmed distal airway volume at FRC and pre-BD FVC [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed distal airway volume at FRC and pre-BD FVC
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	40
Correlation between untrimmed distal airway volume at FRC and pre-BD FVC [units: Correlation coefficient] Number (95% Confidence Interval)	0.4706 (0.1806 to 0.6789)

No statistical analysis provided for Correlation between untrimmed distal airway volume at FRC and pre-BD FVC

23. Secondary Outcome Measure: Correlation between untrimmed total lung volume at TLC and pre-BD FVC [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total lung volume at TLC and pre-BD FVC
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	43
Correlation between untrimmed total lung volume at TLC and pre-BD FVC [units: Correlation coefficient] Number (95% Confidence Interval)	0.4947 (0.2227 to 0.6891)

No statistical analysis provided for Correlation between untrimmed total lung volume at TLC and pre-BD FVC

24. Secondary Outcome Measure: Correlation between untrimmed total lung volume at FRC and pre-BD FVC [ Time Frame: At Baseline (Week 0) ]

Measure Type	Secondary
Measure Name	Correlation between untrimmed total lung volume at FRC and pre-BD FVC
Measure Description	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)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline endpoints analysis set included all participants who had baseline measurements and who had at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	40
Correlation between untrimmed total lung volume at FRC and pre-BD FVC [units: Correlation coefficient] Number (95% Confidence Interval)	0.1451 (-0.1761 to 0.4354)

No statistical analysis provided for Correlation between untrimmed total lung volume at FRC and pre-BD FVC

25. Secondary Outcome Measure: Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FEV1
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FEV1 [units: mL] Mean (95% Confidence Interval)
No adjustment for pre-BD FEV1	0.05 (0.00 to 0.11)
Adjusted for pre-BD FEV1	0.06 (0.00 to 0.12)

No statistical analysis provided for Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FEV1

26. Secondary Outcome Measure: Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FEV1
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FEV1 [units: Scores on a scale] Mean (95% Confidence Interval)
No adjustment for pre-BD FEV1	4.38 (-2.87 to 11.63)
Adjusted for pre-BD FEV1	5.97 (-1.75 to 13.69)

No statistical analysis provided for Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FEV1

27. Secondary Outcome Measure: Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FEV1
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	34
Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FEV1 [units: Percentage of air trapping] Mean (95% Confidence Interval)
No adjustment for pre-BD FEV1	3.18 (-3.65 to 10.01)
Adjusted for pre-BD FEV1	5.24 (-1.23 to 11.71)

No statistical analysis provided for Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FEV1

28. Secondary Outcome Measure: Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FEV1
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FEV1 [units: mL] Mean (95% Confidence Interval)
No adjustment for pre-BD FEV1	5.29 (-1.39 to 11.97)
Adjusted for pre-BD FEV1	5.61 (-1.27 to 12.48)

No statistical analysis provided for Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FEV1

29. Secondary Outcome Measure: Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FEV1
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FEV1 [units: mL] Mean (95% Confidence Interval)
Untrimmed distal airway volume at TLC: No adjustment for pre-BD FEV1	2.20 (-1.09 to 5.49)
Untrimmed distal airway volume at TLC: Adjusted for pre-BD FEV1	0.61 (-2.65 to 3.88)
Untrimmed distal airway volume at FRC: No adjustment for pre-BD FEV1	-1.28 (-2.82 to 0.27)
Untrimmed distal airway volume at FRC: Adjusted for pre-BD FEV1	-1.52 (-3.14 to 0.09)

No statistical analysis provided for Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FEV1

30. Secondary Outcome Measure: Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FEV1 [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FEV1
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FEV1 [units: Litre] Mean (95% Confidence Interval)
Untrimmed total lung volume at TLC: No adjustment for pre-BD FEV1	0.11 (-0.62 to 0.84)
Untrimmed total lung volume at TLC: Adjusted for pre-BD FEV1	0.13 (-0.61 to 0.88)
Untrimmed total lung volume at FRC: No adjustment for pre-BD FEV1	0.52 (-0.16 to 1.21)
Untrimmed total lung volume at FRC: Adjusted for pre-BD FEV1	0.37 (-0.25 to 0.99)

No statistical analysis provided for Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FEV1

31. Secondary Outcome Measure: Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FVC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FVC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FVC [units: mL] Mean (95% Confidence Interval)
No adjustment for pre-BD FVC	0.05 (0.00 to 0.11)
Adjusted for pre-BD FVC	0.05 (-0.01 to 0.11)

No statistical analysis provided for Change from baseline in untrimmed total mucus volume measured at TLC with and without adjustment for pre-BD FVC

32. Secondary Outcome Measure: Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FVC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FVC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FVC [units: Scores on a scale] Mean (95% Confidence Interval)
No adjustment for pre-BD FVC	4.38 (-2.87 to 11.63)
Adjusted for pre-BD FVC	4.65 (-3.00 to 12.30)

No statistical analysis provided for Change from baseline in untrimmed total mucus plugs score at TLC with and without adjustment for pre-BD FVC

33. Secondary Outcome Measure: Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FVC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FVC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	34
Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FVC [units: Percentage of air trapping] Mean (95% Confidence Interval)
No adjustment for pre-BD FVC	3.18 (-3.65 to 10.01)
Adjusted for pre-BD FVC	4.36 (-2.06 to 10.79)

No statistical analysis provided for Change from baseline in untrimmed total air trapping at FRC with and without adjustment for pre-BD FVC

34. Secondary Outcome Measure: Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FVC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FVC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FVC [units: mL] Mean (95% Confidence Interval)
No adjustment for pre-BD FVC	5.29 (-1.39 to 11.97)
Adjusted for pre-BD FVC	6.08 (-0.60 to 12.76)

No statistical analysis provided for Change from baseline in trimmed distal airway wall volume at TLC with and without adjustment for pre-BD FVC

35. Secondary Outcome Measure: Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FVC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FVC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FVC [units: mL] Mean (95% Confidence Interval)
Untrimmed distal airway volume at TLC: No adjustment for pre-BD FVC	2.20 (-1.09 to 5.49)
Untrimmed distal airway volume at TLC: Adjusted for pre-BD FVC	1.22 (-2.30 to 4.73)
Untrimmed distal airway volume at FRC: No adjustment for pre-BD FVC	-1.28 (-2.82 to 0.27)
Untrimmed distal airway volume at FRC: Adjusted for pre-BD FVC	-1.28 (-2.93 to 0.37)

No statistical analysis provided for Change from baseline in untrimmed distal airway volume with and without adjustment for pre-BD FVC

36. Secondary Outcome Measure: Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FVC [ Time Frame: Baseline and Week 13 ]

Measure Type	Secondary
Measure Name	Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FVC
Measure Description	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
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	39
Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FVC [units: Litre] Mean (95% Confidence Interval)
Untrimmed total lung volume at TLC: No adjustment for pre-BD FVC	0.11 (-0.62 to 0.84)
Untrimmed total lung volume at TLC: Adjusted for pre-BD FVC	0.11 (-0.63 to 0.85)
Untrimmed total lung volume at FRC: No adjustment for pre-BD FVC	0.52 (-0.16 to 1.21)
Untrimmed total lung volume at FRC: Adjusted for pre-BD FVC	0.40 (-0.22 to 1.02)

No statistical analysis provided for Change from baseline in untrimmed total lung volume with and without adjustment for pre-BD FVC

37. Secondary Outcome Measure: Number of participants with adverse events (AEs) [ Time Frame: From screening (Day -21) to follow-up (up to 1.9 years) ]

Measure Type	Secondary
Measure Name	Number of participants with adverse events (AEs)
Measure Description	The safety and tolerability of benralizumab was assessed.
Time Frame	From screening (Day -21) to follow-up (up to 1.9 years)
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The safety analysis set consisted of all participants who had received at least one dose of study intervention.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Measured Values

	Benralizumab
Number of Participants Analyzed [units:participants]	45
Number of participants with adverse events (AEs) [units: Participants]
Any AE	17
Any serious adverse event (SAE)	2
Any SAE with outcome death	0
Any AE leading to discontinuation of study intervention	1
Any possibly related AE	3

No statistical analysis provided for Number of participants with adverse events (AEs)

Serious Adverse Events

Time Frame	From screening (Day -21) to follow-up (up to 1.9 years)
Additional Description	The Safety analysis set consisted of all participants who had received at least one dose of investigational product.

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Serious Adverse Events

Benralizumab

Total, serious adverse events

# participants affected / at risk

2/45 (4.44%)

Infections and infestations

Respiratory tract infection¹

# participants affected / at risk

1/45 (2.22%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹

# participants affected / at risk

1/45 (2.22%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA v27.0

Other Adverse Events

Time Frame	From screening (Day -21) to follow-up (up to 1.9 years)
Additional Description	The Safety analysis set consisted of all participants who had received at least one dose of investigational product.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Benralizumab	Participants received 3 doses of benralizumab 30 mg as subcutaneous injection once every 4 weeks (Week 0, Week 4, and Week 8).

Other Adverse Events

Benralizumab

Total, other (not including serious) adverse events

# participants affected / at risk

3/45 (6.67%)

Infections and infestations

Gastroenteritis¹

# participants affected / at risk

3/45 (6.67%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA v27.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No unpublished information contained herein may be disclosed without prior written approval from AstraZeneca AB.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

Download
Redacted CSP
Download
Redacted CSR synopsis
Download
Redacted SAP
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

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