Efficacy and Safety Study of Benralizumab to Reduce OCS Use in Patients with Uncontrolled Asthma on High Dose Inhaled Corticosteroid plus LABA and Chronic OCS Therapy

Study identifier:D3250C00020

ClinicalTrials.gov identifier:NCT02075255

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Multicenter, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase 3 Efficacy and Safety Study of benralizumab (MEDI-563) to Reduce Oral Corticosteroid Use in Patients with Uncontrolled Asthma on High Dose Inhaled Corticosteroid plus Long-acting β2 Agonist and Chronic Oral Corticosteroid Therapy (ZONDA)

Medical condition

asthma

Phase

Phase 3

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

220

Study type

Interventional

Age

18 Years - 75 Years

Date

Study Start Date: 28 Apr 2014

Primary Completion Date: 08 Aug 2016

Study Completion Date: 08 Aug 2016

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 May 2018 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

1.Provision of informed consent prior to any study specific procedures.
2.Female and male aged from 18 to 75 years, inclusively.
3. History of physician-diagnosed asthma requiring treatment with medium dose ICS and LABA.
4.Elevated level of peripheral blood eosinophil
5. Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
6. Chronic oral corticosteroid therapy for at least 6 continuous months
directly preceding Visit 1. Subjects must be on doses equivalent to 7.5 – 40 mg/day of prednisolone/prednisone at Visit 1 and be on a stable dose for at least 2 weeks prior to randomization. Patients must agree to switch to study required
prednisone/prednisolone as their oral corticosteroid for the duration of the study.
7.Patients with documented failures of OCS reduction within 6 months prior to Visit 1 will not be required to proceed through the dose optimization phase during run-in.
8. Morning pre-bronchodilator (Pre-BD) FEV1 of <80% predicted
9. Evidence of asthma as documented by either:
Airway reversibility (FEV1 ≥12% and 200 mL) demonstrated at Visit 1, Visit 2,
or Visit 3 using the Maximum Post-bronchodilator Procedure OR
Documented reversibility in the previous 24 months prior to Visit 1 OR Airway hyperresponsiveness (PC20 FEV1 methacholine concentration ≤8mg/mL) documented in the previous 12 months prior to planned date of randomization OR Airflow variability in clinic FEV1 ≥20% between 2 consecutive clinic visits documented in the 12 months prior to the planned date of randomization (FEV1 recorded during an exacerbation should not be considered for this criterion).
All patients must have reversibility testing performed before randomization to establish a baseline characteristic.
If patients do not demonstrate airway reversibility at either Visit 1 or Visit 2 and this is needed to qualify the patient for randomization, the site should reiterate the need to withhold short- and long-acting bronchodilators prior to Visit 3 in an effort to meet this inclusion criterion.
10. At least 1 documented asthma exacerbation in the previous 12 months prior to the date informed consent is obtained
11. Optimized OCS dose reached at least 2 weeks prior to randomization
12. Additional asthma controller medication must not have been initiated during run in/optimization period (not applicable for management of exacerbations during screening/ run in optimization phase)
13. At least 70% compliance with OCS use
14. At least 70% compliance with usual asthma controller ICS-LABA
15. Minimum 70% (i.e. 10 of 14 days) compliance with asthma daily diary (morning and evening diary)

Exclusion Criteria

1. Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
− Affect the safety of the patient throughout the study
− Influence the findings of the studies or their interpretations
− Impede the patient’s ability to complete the entire duration of study
3. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
4. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during run-in/optimization period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient’s ability to complete entire duration of the study
5.History of life-threatening asthma
6. Asthma control reached at an OCS dose of ≤5mg during run-in/OCS optimization phase
7. Qualifies for 3 consecutive dose reductions at Visits 2-4 and continues to meet OCS dose reduction criteria at Visit 5
8. Receipt of oral corticosteroids, other than prednisone or prednisolone, as the maintenance oral steroid controller for asthma symptoms from Visit 1 and throughout the study.
9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period

Location

Research Site

Pittsburgh, PA, United States, 15213

Location

Research Site

CABA, Argentina, 1426

Location

Research Site

Quillota, Chile

Location

Research Site

Talcahuano, Chile, 4270918

Location

Research Site

Orlando, FL, United States, 32825

Location

Research Site

Iowa City, IA, United States, 52242

Location

Research Site

Winston-Salem, NC, United States, 27103

Location

Research Site

Rochester, MN, United States, 55905

Arms	Assigned Interventions
Experimental: Benralizumab Arm A Benralizumab administered subcutaneously every 4 weeks	Biological/Vaccine: Benralizumab Benralizumab administered subcutaneously every 4 weeks
Experimental: Benralizumab Arm B Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind.	Biological/Vaccine: Benralizumab Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind.
Placebo Comparator: Placebo Placebo administered subcutaneously every 4 weeks	Biological/Vaccine: Placebo Placebo subcutaneously on study week 0 until study week 24 inclusive.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
369 participants signed informed consent. 271 entered run in/OCS optimization period. 220 participants were randomized to receive treatment with benralizumab 30 mg Q4W, Q8W, or placebo. Of the 220 patients randomised, all (100.0%) received treatment with study drug

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Participant Flow: Overall Study

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
STARTED	72	73	75
COMPLETED	68	69	72
NOT COMPLETED	4	4	3
Study specific withdrawal criteria	0	1	1
Withdrawal by Subject	4	1	0
Lost to Follow-up	0	0	1
Adverse Event	0	0	1
Death	0	2	0

Baseline Characteristics

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

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Baseline Measures

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo	Total
Number of Participants [units: Participants]	72	73	75	220
Age Continuous [units: Years] Mean ± Standard Deviation	50.2 ± 12.0	52.9 ± 10.1	49.9 ± 11.7	51.0 ± 11.3
Gender, Male/Female [units: ]
Female	40	47	48	135
Male	32	26	27	85

Outcome Measures

1. Primary Outcome Measure: Percentage reduction in final OCS dose compared with baseline while maintaining asthma control [ Time Frame: Week 28 ]

Measure Type	Primary
Measure Name	Percentage reduction in final OCS dose compared with baseline while maintaining asthma control
Measure Description	Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose–final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Time Frame	Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Percentage reduction in final OCS dose compared with baseline while maintaining asthma control [units: Percent] Median (95% Confidence Interval)

Statistical Analysis 1 for Percentage reduction in final OCS dose compared with baseline while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	<0.001
Median Difference (Final Values)^[5]	33.3
95% Confidence Interval	( 16.70 to 50.00 )

[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]	Other relevant estimation information:
	Hodges-Lehmann estimate is used.

Statistical Analysis 2 for Percentage reduction in final OCS dose compared with baseline while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	<0.001
Median Difference (Final Values)^[5]	37.50
95% Confidence Interval	( 20.80 to 50.00 )

[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]	Other relevant estimation information:
	Hodges Lehmann estimate is used.

2. Secondary Outcome Measure: Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose while maintaining asthma control [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose while maintaining asthma control
Measure Description	Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose.
Time Frame	Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose while maintaining asthma control [units: ]
>=90% reduction	24	27	9
>=75% reduction	38	37	15
>=50% reduction	48	48	28
>0% reduction	55	58	40
No change or any increase	17	15	35

Statistical Analysis 1 for Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Other [proportional odds model]
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	4.09
95% Confidence Interval	( 2.22 to 7.57 )

[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:
	Controlling for treatment group, region, and baseline OCS dose.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Other [proportional odds model]
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	4.12
95% Confidence Interval	( 2.22 to 7.63 )

[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:
	Controlling for treatment group, region, and baseline OCS dose.
[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]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Percentage reduction in final OCS dose compared with baseline while maintaining asthma control for patients with baseline eosinophils >=300/uL [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	Percentage reduction in final OCS dose compared with baseline while maintaining asthma control for patients with baseline eosinophils >=300/uL
Measure Description	Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose–final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Time Frame	Week 28
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.
Full analysis set, baseline blood eosinophil >=300/uL

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	62	61	64
Percentage reduction in final OCS dose compared with baseline while maintaining asthma control for patients with baseline eosinophils >=300/uL [units: Percent] Median (95% Confidence Interval)

Statistical Analysis 1 for Percentage reduction in final OCS dose compared with baseline while maintaining asthma control for patients with baseline eosinophils >=300/uL

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	<0.001
Median Difference (Final Values)^[5]	50.00
95% Confidence Interval	( 25.00 to 66.70 )

[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]	Other relevant estimation information:
	Hodges Lehmann estimate is used.

Statistical Analysis 2 for Percentage reduction in final OCS dose compared with baseline while maintaining asthma control for patients with baseline eosinophils >=300/uL

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Wilcoxon (Mann-Whitney)
P-Value^[4]	<0.001
Median Difference (Final Values)^[5]	50.00
95% Confidence Interval	( 25.00 to 66.70 )

[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]	Other relevant estimation information:
	Hodges Lehmann estimate is used.

4. Secondary Outcome Measure: The percentage of patients with ≥50% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	The percentage of patients with ≥50% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control
Measure Description	Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose–final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Time Frame	Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
The percentage of patients with ≥50% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control [units: ]	48	48	28

Statistical Analysis 1 for The percentage of patients with ≥50% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	3.59
95% Confidence Interval	( 1.79 to 7.22 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The percentage of patients with ≥50% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	3.03
95% Confidence Interval	( 1.57 to 5.86 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: The proportion of eligible patients with ≥100% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	The proportion of eligible patients with ≥100% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control
Measure Description	Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose–final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Time Frame	Week 28
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.
Full analysis set, eligible for 100% reduction (ie, patients with baseline OCS dose <= 12.5 mg)

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	39	42	42
The proportion of eligible patients with ≥100% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control [units: Participants]

Statistical Analysis 1 for The proportion of eligible patients with ≥100% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	5.23
95% Confidence Interval	( 1.92 to 14.21 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The proportion of eligible patients with ≥100% reduction in average daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.002
Odds Ratio (OR)^[5]	4.19
95% Confidence Interval	( 1.58 to 11.12 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: The proportion of patients with ≤5.0 mg reduction on daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control. [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	The proportion of patients with ≤5.0 mg reduction on daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control.
Measure Description	Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Time Frame	Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
The proportion of patients with ≤5.0 mg reduction on daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control. [units: Participants]

Statistical Analysis 1 for The proportion of patients with ≤5.0 mg reduction on daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control.

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.012
Odds Ratio (OR)^[5]	0.42
95% Confidence Interval	( 0.21 to 0.83 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The proportion of patients with ≤5.0 mg reduction on daily OCS dose at Visit 14 compared with baseline dose at Visit 6, while maintaining asthma control.

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.053
Odds Ratio (OR)^[5]	0.52
95% Confidence Interval	( 0.27 to 1.01 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: The proportion of patients with average final OCS dose ≤5.0 mg daily at Visit 14, while maintaining asthma control [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	The proportion of patients with average final OCS dose ≤5.0 mg daily at Visit 14, while maintaining asthma control
Measure Description	Final OCS dose is the dose at Week 28. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.
Time Frame	Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
The proportion of patients with average final OCS dose ≤5.0 mg daily at Visit 14, while maintaining asthma control [units: Participants]

Statistical Analysis 1 for The proportion of patients with average final OCS dose ≤5.0 mg daily at Visit 14, while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	3.16
95% Confidence Interval	( 1.60 to 6.23 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The proportion of patients with average final OCS dose ≤5.0 mg daily at Visit 14, while maintaining asthma control

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.002
Odds Ratio (OR)^[5]	2.74
95% Confidence Interval	( 1.41 to 5.31 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Number and percentage of patients with ≥1 asthma exacerbation [ Time Frame: Immediately following the randomisation through Study Week 28 ]

Measure Type	Secondary
Measure Name	Number and percentage of patients with ≥1 asthma exacerbation
Measure Description	Number and percentage of patients with at least one post randomisation asthma exacerbation.
Time Frame	Immediately following the randomisation through Study Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Number and percentage of patients with ≥1 asthma exacerbation [units: ]	19	17	39

Statistical Analysis 1 for Number and percentage of patients with ≥1 asthma exacerbation

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	0.001
Odds Ratio (OR)^[5]	0.32
95% Confidence Interval	( 0.16 to 0.65 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Number and percentage of patients with ≥1 asthma exacerbation

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Cochran-Mantel-Haenszel
P-Value^[4]	<0.001
Odds Ratio (OR)^[5]	0.28
95% Confidence Interval	( 0.14 to 0.56 )

[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:
	Controlling for region.
[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]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: Time to the first asthma exacerbation [ Time Frame: The time from randomisation to the date of first asthma exacerbation over 28 weeks ]

Measure Type	Secondary
Measure Name	Time to the first asthma exacerbation
Measure Description	Time to the first occurrence of asthma exacerbation post randomisation
Time Frame	The time from randomisation to the date of first asthma exacerbation over 28 weeks
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Time to the first asthma exacerbation [units: Days] Median (95% Confidence Interval)

Statistical Analysis 1 for Time to the first asthma exacerbation

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Regression, Cox
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.39
95% Confidence Interval	( 0.22 to 0.66 )

[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:
	Including covariates treatment group, region, number of exacerbations in the previous year.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Time to the first asthma exacerbation

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Regression, Cox
P-Value^[4]	<0.001
Hazard Ratio (HR)^[5]	0.32
95% Confidence Interval	( 0.17 to 0.57 )

[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:
	Including covariates treatment group, region, number of exacerbations in the previous year.
[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]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: Time to the first asthma exacerbation requiring hospitalization or ER visit [ Time Frame: The time from randomisation to the date of first asthma exacerbation associated with hospitalization or ER over 28 weeks. ]

Measure Type	Secondary
Measure Name	Time to the first asthma exacerbation requiring hospitalization or ER visit
Measure Description	Time to the first exacerbation requiring hospitalization or ER visit post randomisation
Time Frame	The time from randomisation to the date of first asthma exacerbation associated with hospitalization or ER over 28 weeks.
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Time to the first asthma exacerbation requiring hospitalization or ER visit [units: Days] Median (95% Confidence Interval)

Statistical Analysis 1 for Time to the first asthma exacerbation requiring hospitalization or ER visit

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Regression, Cox
P-Value^[4]	0.291
Hazard Ratio (HR)^[5]	0.53
95% Confidence Interval	( 0.14 to 1.64 )

[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:
	Including covariates treatment group, region, any exacerbations in the previous year requiring hospitalization or ER visit.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Time to the first asthma exacerbation requiring hospitalization or ER visit

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Regression, Cox
P-Value^[4]	0.042
Hazard Ratio (HR)^[5]	0.12
95% Confidence Interval	( 0.01 to 0.63 )

[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:
	Including covariates treatment group, region, any exacerbations in the previous year requiring hospitalization or ER visit.
[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]	Other relevant estimation information:
	No text entered.

11. Secondary Outcome Measure: The Annualized rate of asthma exacerbation [ Time Frame: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up ]

Measure Type	Secondary
Measure Name	The Annualized rate of asthma exacerbation
Measure Description	The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator adjusted by the time of follow-up.
Time Frame	The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
The Annualized rate of asthma exacerbation [units: events/year] Least Squares Mean (95% Confidence Interval)

Statistical Analysis 1 for The Annualized rate of asthma exacerbation

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Other [negative binomial model]
P-Value^[4]	0.003
Other^[5]	0.45
95% Confidence Interval	( 0.27 to 0.76 )

[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:
	Including covariates treatment group, region, number of exacerbations in the previous year. The log of follow-up time is used as offset variable.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The Annualized rate of asthma exacerbation

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Other [negative binomial model]
P-Value^[4]	<0.001
Other^[5]	0.3
95% Confidence Interval	( 0.17 to 0.53 )

[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:
	Including covariates treatment group, region, number of exacerbations in the previous year. The log of follow-up time is used as offset variable.
[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]	Other relevant estimation information:
	No text entered.

12. Secondary Outcome Measure: The annualized rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization [ Time Frame: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up ]

Measure Type	Secondary
Measure Name	The annualized rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization
Measure Description	The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator that are associated with an emergency room visit or a hospitalization adjusted by the time of follow-up.
Time Frame	The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
The annualized rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization [units: events/year] Least Squares Mean (95% Confidence Interval)

Statistical Analysis 1 for The annualized rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Other [negative binomial model]
P-Value^[4]	0.187
Other^[5]	0.44
95% Confidence Interval	( 0.13 to 1.49 )

[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:
	Covariates include treatment, region, any exacerbations in the previous year requiring hospitalization/ER. Log of follow-up time is the offset.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for The annualized rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Other [negative binomial model]
P-Value^[4]	0.018
Other^[5]	0.07
95% Confidence Interval	( 0.01 to 0.63 )

[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:
	Covariates include treatment, region, any exacerbations in the previous year requiring hospitalization/ER. Log of follow-up time is the offset.
[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]	Other relevant estimation information:
	No text entered.

13. Secondary Outcome Measure: Number of days in hospital due to asthma [ Time Frame: The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up ]

Measure Type	Secondary
Measure Name	Number of days in hospital due to asthma
Measure Description	Number of days in hospital due to asthma, if none, 0 day is considered
Time Frame	The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Number of days in hospital due to asthma [units: Days] Mean (Standard Deviation)

No statistical analysis provided for Number of days in hospital due to asthma

14. Secondary Outcome Measure: Change from baseline to week 28 in pre-bronchodilator FEV1 [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in pre-bronchodilator FEV1
Measure Description	Baseline is defined as the last non-missing value prior to the first dose of study treatment. Change from baseline to Week 28 in two treatment groups is compared to placebo group.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	68	68	73
Change from baseline to week 28 in pre-bronchodilator FEV1 [units: Liter] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in pre-bronchodilator FEV1

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.153
Mean Difference (Final Values)^[5]	0.105
95% Confidence Interval	( -0.040 to 0.251 )

[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:
	Including covariates: treatment group, region, baseline pre-BD FEV1 value, visit, and visit by treatment interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in pre-bronchodilator FEV1

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.129
Mean Difference (Final Values)^[5]	0.112
95% Confidence Interval	( -0.033 to 0.258 )

[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:
	Including covariates: treatment group, region, baseline pre-BD FEV1 value, visit, and visit by treatment interaction.
[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]	Other relevant estimation information:
	No text entered.

15. Secondary Outcome Measure: Change from baseline to week 28 in asthma symptom scores (Total) [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in asthma symptom scores (Total)
Measure Description	Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	67	68	67
Change from baseline to week 28 in asthma symptom scores (Total) [units: Scores on a scale] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in asthma symptom scores (Total)

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.947
Mean Difference (Final Values)^[5]	-0.01
95% Confidence Interval	( -0.35 to 0.32 )

[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:
	Include covariates: treatment group, baseline asthma symptom score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in asthma symptom scores (Total)

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.291
Mean Difference (Final Values)^[5]	-0.18
95% Confidence Interval	( -0.51 to 0.16 )

[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:
	Include covariates: treatment group, baseline asthma symptom score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

16. Secondary Outcome Measure: Change from baseline to week 28 in asthma symptom scores (Daytime) [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in asthma symptom scores (Daytime)
Measure Description	Asthma symptoms during daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma). Lower score (0) is indicating better asthma symptom, while higher score (3) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	67	69	69
Change from baseline to week 28 in asthma symptom scores (Daytime) [units: Scores on a scale] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in asthma symptom scores (Daytime)

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.998
Mean Difference (Final Values)^[5]	-0.00
95% Confidence Interval	( -0.18 to 0.18 )

[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:
	Include covariates: treatment group, baseline asthma symptom score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in asthma symptom scores (Daytime)

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.177
Mean Difference (Final Values)^[5]	-0.12
95% Confidence Interval	( -0.30 to 0.05 )

[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:
	Include covariates: treatment group, baseline asthma symptom score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

17. Secondary Outcome Measure: Change from baseline to week 28 in asthma symptom scores (Nighttime) [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in asthma symptom scores (Nighttime)
Measure Description	Asthma symptoms during night time are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma). Lower score (0) is indicating better asthma symptom, while higher score (3) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	67	68	67
Change from baseline to week 28 in asthma symptom scores (Nighttime) [units: Scores on a scale] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in asthma symptom scores (Nighttime)

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.973
Mean Difference (Final Values)^[5]	-0.00
95% Confidence Interval	( -0.17 to 0.17 )

[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:
	Include covariates: treatment group, baseline asthma symptom score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in asthma symptom scores (Nighttime)

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.480
Mean Difference (Final Values)^[5]	-0.06
95% Confidence Interval	( -0.23 to 0.11 )

[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:
	Include covariates: treatment group, baseline asthma symptom score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

18. Secondary Outcome Measure: Change from baseline to week 28 in rescue medication use [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in rescue medication use
Measure Description	Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this will be considered as missing. The number of inhalations (puffs) per day will be calculated as follows: Number of night inhaler puffs + 2 x [number of night nebulizer times] + number of day inhaler puffs + 2 x [number of day nebulizer times].
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	67	68	67
Change from baseline to week 28 in rescue medication use [units: number of puffs per day] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in rescue medication use

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.397
Mean Difference (Final Values)^[5]	-0.43
95% Confidence Interval	( -1.44 to 0.57 )

[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:
	Include covariates: treatment group, baseline total asthma rescue medication use, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in rescue medication use

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.006
Mean Difference (Final Values)^[5]	-1.41
95% Confidence Interval	( -2.42 to -0.41 )

[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:
	Include covariates: treatment group, baseline total asthma rescue medication use, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

19. Secondary Outcome Measure: Change from baseline to week 28 in home lung function (morning peak expiratory flow) [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in home lung function (morning peak expiratory flow)
Measure Description	Morning peak expiratory flow change from baseline to week 28. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	67	68	67
Change from baseline to week 28 in home lung function (morning peak expiratory flow) [units: Liter/min] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in home lung function (morning peak expiratory flow)

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.143
Mean Difference (Final Values)^[5]	19.25
95% Confidence Interval	( -6.58 to 45.07 )

[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:
	Include covariates: treatment group, baseline morning PEF, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in home lung function (morning peak expiratory flow)

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.023
Mean Difference (Final Values)^[5]	30.01
95% Confidence Interval	( 4.26 to 55.76 )

[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:
	Include covariates: treatment group, baseline morning PEF, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

20. Secondary Outcome Measure: Change from baseline to week 28 in home lung function (evening peak expiratory flow) [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in home lung function (evening peak expiratory flow)
Measure Description	Evening peak expiratory flow change from baseline to week 28. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	67	69	66
Change from baseline to week 28 in home lung function (evening peak expiratory flow) [units: Liter/min] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in home lung function (evening peak expiratory flow)

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.237
Mean Difference (Final Values)^[5]	15.19
95% Confidence Interval	( -10.08 to 40.46 )

[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:
	Include covariates: treatment group, baseline evening PEF, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in home lung function (evening peak expiratory flow)

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.014
Mean Difference (Final Values)^[5]	31.52
95% Confidence Interval	( 6.32 to 56.71 )

[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:
	Include covariates: treatment group, baseline evening PEF, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

21. Secondary Outcome Measure: Change from baseline to week 28 in the proportion of nights with awakening due to asthma requiring rescue medication [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in the proportion of nights with awakening due to asthma requiring rescue medication
Measure Description	Baseline is defined as the proportion of nights from the evening of study day -14 to the morning of study day 1.Each timepoint is calculated as bi-weekly proportions based on daily diary data. If more than 50% of data are missing in a 14 day period then this will be considered as missing.Proportion of nights with noctural awakenings is defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	67	68	67
Change from baseline to week 28 in the proportion of nights with awakening due to asthma requiring rescue medication [units: Proportion] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in the proportion of nights with awakening due to asthma requiring rescue medication

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.742
Mean Difference (Final Values)^[5]	0.02
95% Confidence Interval	( -0.08 to 0.11 )

[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:
	Including covariates: treatment group, baseline proportion of nights with noctural awakenings, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in the proportion of nights with awakening due to asthma requiring rescue medication

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.693
Mean Difference (Final Values)^[5]	-0.02
95% Confidence Interval	( -0.11 to 0.07 )

[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:
	Including covariates: treatment group, baseline proportion of nights with noctural awakenings, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

22. Secondary Outcome Measure: Change from baseline to week 28 in ACQ-6 [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline to week 28 in ACQ-6
Measure Description	ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	66	66	67
Change from baseline to week 28 in ACQ-6 [units: Scores on a scale] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline to week 28 in ACQ-6

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.139
Mean Difference (Final Values)^[5]	-0.24
95% Confidence Interval	( -0.55 to 0.08 )

[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:
	Include covariates: treatment group, baseline ACQ-6 score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline to week 28 in ACQ-6

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.001
Mean Difference (Final Values)^[5]	-0.55
95% Confidence Interval	( -0.86 to -0.23 )

[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:
	Include covariates: treatment group, baseline ACQ-6 score, region, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

23. Secondary Outcome Measure: ACQ-6 responders (improvement) at Week 28 [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	ACQ-6 responders (improvement) at Week 28
Measure Description	Improvement is defined as ACQ-6 (End of treatment - baseline) <= -0.5. No change is defined as ACQ-6 (End of treatment - baseline) >-0.5 and <0.5. Deterioration is defined as ACQ-6 (End of treatment - baseline) >= 0.5. ACQ-6 score is defined as the average of the first 6 items of the ACQ questionnaire on symptoms, activity limitations and rescue medication.Scores range from 0 (totally controlled) to 6 (severely uncontrolled). Baseline is defined as the last non-missing value prior to randomisation. End of treatment is defined as week 28. Patients with missing or non-evaluable ACQ-6 at week 28 are considered non-responder.
Time Frame	Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
ACQ-6 responders (improvement) at Week 28 [units: Participants]

Statistical Analysis 1 for ACQ-6 responders (improvement) at Week 28

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.658
Odds Ratio (OR)^[5]	1.165
95% Confidence Interval	( 0.592 to 2.295 )

[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:
	Including covariates: treatment group, baseline ACQ-6 score, region, number of exacerbations in the previous year.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for ACQ-6 responders (improvement) at Week 28

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.155
Odds Ratio (OR)^[5]	1.661
95% Confidence Interval	( 0.826 to 3.340 )

[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:
	Including covariates: treatment group, baseline ACQ-6 score, region, number of exacerbations in the previous year.
[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]	Other relevant estimation information:
	No text entered.

24. Secondary Outcome Measure: Change from baseline at week 28 in AQLQ(S)+12 (Overall) [ Time Frame: Change from baseline at week 28 ]

Measure Type	Secondary
Measure Name	Change from baseline at week 28 in AQLQ(S)+12 (Overall)
Measure Description	AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of >=0.5 are considered clinically meaningful.
Time Frame	Change from baseline at week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	66	67	68
Change from baseline at week 28 in AQLQ(S)+12 (Overall) [units: Scores on a scale] Mean (Standard Deviation)

Statistical Analysis 1 for Change from baseline at week 28 in AQLQ(S)+12 (Overall)

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.151
Mean Difference (Final Values)^[5]	0.23
95% Confidence Interval	( -0.08 to 0.53 )

[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:
	Including covariates: treatment group, region, baseline AQLQ(S)+12 score, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Change from baseline at week 28 in AQLQ(S)+12 (Overall)

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	0.004
Mean Difference (Final Values)^[5]	0.45
95% Confidence Interval	( 0.14 to 0.76 )

[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:
	Including covariates: treatment group, region, baseline AQLQ(S)+12 score, visit, and treatment by visit interaction.
[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]	Other relevant estimation information:
	No text entered.

25. Secondary Outcome Measure: AQLQ(s)+12 responders (improvement) at Week 28 [ Time Frame: Week 28 ]

Measure Type	Secondary
Measure Name	AQLQ(s)+12 responders (improvement) at Week 28
Measure Description	AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. Improvement is defined as AQLQ(S)+12 (End of treatment - baseline)>=0.5. No change is defined as AQLQ(S)+12 (End of treatment - baseline) >-0.5 and <0.5. Deterioration is defined as AQLQ(S)+12 (End of treatment - baseline) <= -0.5. Baseline is defined as the last AQLQ(S)+12 score prior to randomisation. End of treatment is defined as week 28. Patients with missing or non-evaluable score at week 28 are considered as non-responder.
Time Frame	Week 28
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.
Full analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
AQLQ(s)+12 responders (improvement) at Week 28 [units: Participants]

Statistical Analysis 1 for AQLQ(s)+12 responders (improvement) at Week 28

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.220
Odds Ratio (OR)^[5]	1.538
95% Confidence Interval	( 0.773 to 3.060 )

[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:
	Including covariates: treatment group, region, baseline AQLQ(S)+12 score, number of exacerbations in the previous year.
[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]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for AQLQ(s)+12 responders (improvement) at Week 28

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.108
Odds Ratio (OR)^[5]	1.783
95% Confidence Interval	( 0.882 to 3.605 )

[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:
	Including covariates: treatment group, region, baseline AQLQ(S)+12 score, number of exacerbations in the previous year.
[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]	Other relevant estimation information:
	No text entered.

26. Secondary Outcome Measure: Extent of Exposure [ Time Frame: From first dose to Week 24 ]

Measure Type	Secondary
Measure Name	Extent of Exposure
Measure Description	Duration of exposure from first dose date to last dose date.
Time Frame	From first dose to Week 24
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.
Safety analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Extent of Exposure [units: Days] Mean (Standard Deviation)

No statistical analysis provided for Extent of Exposure

27. Secondary Outcome Measure: Serum concentration of Benralizumab [ Time Frame: Pre-first dose to Week 36 ]

Measure Type	Secondary
Measure Name	Serum concentration of Benralizumab
Measure Description	Pre-dose serum concentrations at each visit
Time Frame	Pre-first dose to Week 36
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.
PK analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	71	72	0
Serum concentration of Benralizumab [units: ng/mL] Geometric Mean (Geometric Coefficient of Variation)
Baseline (n=69, 71)
Week 4 (n=67, 71)
week 8 (n=66, 69)
Week 12 (n=68, 67)
Week 16 (n=67,67)
Week 24 (n=65, 66)
Week 28 (n=65, 65)
Week 36 (n=2, 4)

No statistical analysis provided for Serum concentration of Benralizumab

28. Secondary Outcome Measure: Anti-drug antibody response [ Time Frame: From baseline to follow-up Week 36 ]

Measure Type	Secondary
Measure Name	Anti-drug antibody response
Measure Description	Number and percentage of patients in different ADA response categories
Time Frame	From baseline to follow-up Week 36
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.
Safety analysis set

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	72	73	75
Anti-drug antibody response [units: ]
Positive at any visit	5	7	6
Baseline and Post-baseline Postive	0	0	3
Only post-baseline positive	5	6	3
Only baseline positive	0	1	0
Persistently positive	4	6	5
Transient positive	1	0	1

No statistical analysis provided for Anti-drug antibody response

29. Secondary Outcome Measure: Percent change from baseline in blood eosinophil counts [ Time Frame: Change from baseline at Week 28 ]

Measure Type	Secondary
Measure Name	Percent change from baseline in blood eosinophil counts
Measure Description	Percent change from baseline in blood eosinophil counts at week 28
Time Frame	Change from baseline at Week 28
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.
Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	63	62	66
Percent change from baseline in blood eosinophil counts [units: percent change] Mean (Standard Deviation)

Statistical Analysis 1 for Percent change from baseline in blood eosinophil counts

Groups^[1]	Benralizumab 30 mg q.4 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.001
Mean Difference (Final Values)^[5]	-162.2
95% Confidence Interval	( -220.1 to -104.3 )

[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:
	Include covariates: treatment group, baseline eosinophil count, region, visit, treatment by visit
[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]	Other relevant estimation information:
	Percent change

Statistical Analysis 2 for Percent change from baseline in blood eosinophil counts

Groups^[1]	Benralizumab 30 mg q.8 weeks, Placebo
Method^[3]	Mixed Models Analysis
P-Value^[4]	<0.001
Mean Difference (Final Values)^[5]	-159.4
95% Confidence Interval	( -217.9 to -100.9 )

[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:
	Include covariates: treatment group, baseline eosinophil count, region, visit, treatment by visit.
[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]	Other relevant estimation information:
	Percent change

30. Secondary Outcome Measure: Total Lung Capacity [ Time Frame: From baseline to Week 28 ]

Measure Type	Secondary
Measure Name	Total Lung Capacity
Measure Description	Change from baseline in total lung capacity
Time Frame	From baseline to Week 28
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.
Global Sputum Substudy

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	22	26	23
Total Lung Capacity [units: Liter] Mean (Standard Deviation)
Week 12 (n=17, 23, 17)
Week 28 (n=14, 18, 15)

No statistical analysis provided for Total Lung Capacity

31. Secondary Outcome Measure: Residual Volume [ Time Frame: From baseline to Week 28 ]

Measure Type	Secondary
Measure Name	Residual Volume
Measure Description	Change from baseline in residual volume
Time Frame	From baseline to Week 28
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.
Global Sputum Substudy

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	22	26	23
Residual Volume [units: Liter] Mean (Standard Deviation)
Week 12 (n=17, 23, 17)
Week 28 (n=14, 18, 15)

No statistical analysis provided for Residual Volume

32. Secondary Outcome Measure: Vital Capacity [ Time Frame: From baseline to Week 28 ]

Measure Type	Secondary
Measure Name	Vital Capacity
Measure Description	Change from baseline in vital capacity
Time Frame	From baseline to Week 28
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.
Global Sputum Substudy

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	22	26	23
Vital Capacity [units: Liter] Mean (Standard Deviation)
Week 12 (n=17, 24, 18)
Week 28 (n=14, 18, 15)

No statistical analysis provided for Vital Capacity

33. Secondary Outcome Measure: Functional Residual Capacity [ Time Frame: From baseline to Week 28 ]

Measure Type	Secondary
Measure Name	Functional Residual Capacity
Measure Description	Change from baseline in functional residual capacity
Time Frame	From baseline to Week 28
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.
Global Sputum Substudy

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	22	26	23
Functional Residual Capacity [units: Liter] Mean (Standard Deviation)
Week 12 (n=17,23, 18)
Week 28 (n=13,18, 15)

No statistical analysis provided for Functional Residual Capacity

34. Secondary Outcome Measure: Inspiratory Capacity [ Time Frame: From baseline to Week 28 ]

Measure Type	Secondary
Measure Name	Inspiratory Capacity
Measure Description	Change from baseline in inspiratory capacity
Time Frame	From baseline to Week 28
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.
Global Sputum Substudy

Reporting Groups

	Description
Benralizumab 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Measured Values

	Benralizumab 30 mg q.4 weeks	Benralizumab 30 mg q.8 weeks	Placebo
Number of Participants Analyzed [units:participants]	22	26	23
Inspiratory Capacity [units: Liter] Mean (Standard Deviation)
Week 12 (n=17, 23, 17)
Week 28 (n=14, 17, 15)

No statistical analysis provided for Inspiratory Capacity

Serious Adverse Events

Time Frame	Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Additional Description	No text entered.

Reporting Groups

	Description
Benra 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benra 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Serious Adverse Events

Benra 30 mg q.4 weeks

Benra 30 mg q.8 weeks

Placebo

Total, serious adverse events

# participants affected / at risk

7/72 (9.72%)

7/73 (9.59%)

14/75 (18.67%)

Cardiac disorders

Atrial fibrillation¹,^†

# participants affected / at risk

0/72 (0.00%)

1/73 (1.37%)

0/75 (0.00%)

# events

Cardiac disorders

Atrial flutter¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

1/75 (1.33%)

# events

Cardiac disorders

Cardiac failure acute¹,^†

# participants affected / at risk

0/72 (0.00%)

1/73 (1.37%)

0/75 (0.00%)

# events

Cardiac disorders

Pericarditis¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

1/75 (1.33%)

# events

Gastrointestinal disorders

Oesophagitis¹,^†

# participants affected / at risk

0/72 (0.00%)

1/73 (1.37%)

0/75 (0.00%)

# events

Gastrointestinal disorders

Umbilical hernia¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

General disorders and administration site conditions

Adverse drug reaction¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

Hepatobiliary disorders

Gallbladder polyp¹,^†

# participants affected / at risk

0/72 (0.00%)

1/73 (1.37%)

0/75 (0.00%)

# events

Immune system disorders

Hypersensitivity¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

Infections and infestations

Atypical pneumonia¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

1/75 (1.33%)

# events

Infections and infestations

Chronic sinusitis¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

1/75 (1.33%)

# events

Infections and infestations

Colonic abscess¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

1/75 (1.33%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

2/75 (2.67%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

0/72 (0.00%)

2/73 (2.74%)

3/75 (4.00%)

# events

Infections and infestations

Pneumonia staphylococcal¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

1/75 (1.33%)

# events

Infections and infestations

Urinary tract infection bacterial¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

Infections and infestations

Urosepsis¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Intervertebral disc protrusion¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

Nervous system disorders

Presyncope¹,^†

# participants affected / at risk

0/72 (0.00%)

1/73 (1.37%)

0/75 (0.00%)

# events

Renal and urinary disorders

Nephrolithiasis¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

3/72 (4.17%)

1/73 (1.37%)

4/75 (5.33%)

# events

Respiratory, thoracic and mediastinal disorders

Sleep apnoea syndrome¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

1/75 (1.33%)

# events

Respiratory, thoracic and mediastinal disorders

Status asthmaticus¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

3/75 (4.00%)

# events

Skin and subcutaneous tissue disorders

Dermatitis atopic¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

0/75 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.1

Other Adverse Events

Time Frame	Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	3%

Reporting Groups

	Description
Benra 30 mg q.4 weeks	Benralizumab administered subcutaneously every 4 weeks
Benra 30 mg q.8 weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
Placebo	Placebo administered subcutaneously

Other Adverse Events

Benra 30 mg q.4 weeks

Benra 30 mg q.8 weeks

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

34/72 (47.22%)

34/73 (46.58%)

49/75 (65.33%)

Ear and labyrinth disorders

Vertigo¹,^†

# participants affected / at risk

1/72 (1.39%)

3/73 (4.11%)

2/75 (2.67%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

1/72 (1.39%)

0/73 (0.00%)

3/75 (4.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

5/72 (6.94%)

8/73 (10.96%)

12/75 (16.00%)

# events

Infections and infestations

Influenza¹,^†

# participants affected / at risk

3/72 (4.17%)

1/73 (1.37%)

5/75 (6.67%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

11/72 (15.28%)

12/73 (16.44%)

15/75 (20.00%)

# events

Infections and infestations

Oral candidiasis¹,^†

# participants affected / at risk

0/72 (0.00%)

0/73 (0.00%)

4/75 (5.33%)

# events

Infections and infestations

Rhinitis¹,^†

# participants affected / at risk

2/72 (2.78%)

6/73 (8.22%)

2/75 (2.67%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

5/72 (6.94%)

4/73 (5.48%)

8/75 (10.67%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

4/72 (5.56%)

5/73 (6.85%)

5/75 (6.67%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

2/72 (2.78%)

2/73 (2.74%)

4/75 (5.33%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

5/72 (6.94%)

6/73 (8.22%)

4/75 (5.33%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

6/72 (8.33%)

1/73 (1.37%)

14/75 (18.67%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

2/72 (2.78%)

1/73 (1.37%)

4/75 (5.33%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

2/72 (2.78%)

1/73 (1.37%)

4/75 (5.33%)

# events

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

2/72 (2.78%)

3/73 (4.11%)

2/75 (2.67%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 18.1

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: ≥ 60 days prior to submission of material for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ’s Confidential Information without AZ’s written approval. AZ can request Inst. and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication or presentation.

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:	Mitchell Goldman, Global Clinical Lead Benralizumab
Organization:	AstraZeneca
Phone	+1 301 398 0323
E-mail:	[email protected]

Documents available

CSP redacted
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

null Clinical Study Information

+1 800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Parameswaran Nair

St Joseph's Healthcare Hamilton Firestone Institute for Respiratory Health 50 Charlton Avenue East Hamilton

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site