Trial Outcomes & Findings for 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 (NCT NCT02075255)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

220 participants

Primary outcome timeframe

Week 28

Results posted on

2018-06-08

Participant Flow

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

Participant milestones

Participant milestones
Measure	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
Overall Study STARTED	72	73	75
Overall Study COMPLETED	68	69	72
Overall Study NOT COMPLETED	4	4	3

Reasons for withdrawal

Reasons for withdrawal
Measure	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
Overall Study Study specific withdrawal criteria	0	1	1
Overall Study Withdrawal by Subject	4	1	0
Overall Study Lost to Follow-up	0	0	1
Overall Study Adverse Event	0	0	1
Overall Study Death	0	2	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously	Total n=220 Participants Total of all reporting groups
Age, Continuous	50.2 Years STANDARD_DEVIATION 12.0 • n=93 Participants	52.9 Years STANDARD_DEVIATION 10.1 • n=4 Participants	49.9 Years STANDARD_DEVIATION 11.7 • n=27 Participants	51.0 Years STANDARD_DEVIATION 11.3 • n=483 Participants
Sex: Female, Male Female	40 Participants n=93 Participants	47 Participants n=4 Participants	48 Participants n=27 Participants	135 Participants n=483 Participants
Sex: Female, Male Male	32 Participants n=93 Participants	26 Participants n=4 Participants	27 Participants n=27 Participants	85 Participants n=483 Participants

PRIMARY outcome

Timeframe: Week 28

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control	75.00 Percent Interval 50.0 to 83.3	75.00 Percent Interval 60.0 to 87.5	25.00 Percent Interval 0.0 to 33.3

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set

Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control >=90% reduction	24 Participants	27 Participants	9 Participants
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control >=75% reduction	38 Participants	37 Participants	15 Participants
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control >=50% reduction	48 Participants	48 Participants	28 Participants
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control >0% reduction	55 Participants	58 Participants	40 Participants
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control No change or any increase	17 Participants	15 Participants	35 Participants

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set, baseline blood eosinophil \>=300/uL

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=62 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=61 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=64 Participants Placebo administered subcutaneously
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control for Patients With Baseline Eosinophils >=300/uL	75.00 Percent Interval 60.0 to 100.0	75.00 Percent Interval 60.0 to 91.7	0.00 Percent Interval 0.0 to 28.6

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
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	48 Participants	48 Participants	28 Participants

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set, eligible for 100% reduction (ie, patients with baseline OCS dose \<= 12.5 mg)

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=39 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=42 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=42 Participants Placebo administered subcutaneously
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	22 Participants	22 Participants	8 Participants

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
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.	22 Participants	25 Participants	38 Participants

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
The Proportion of Patients With Average Final OCS Dose ≤5.0 mg Daily at Visit 14, While Maintaining Asthma Control	44 Participants	43 Participants	25 Participants

SECONDARY outcome

Timeframe: Immediately following the randomisation through Study Week 28

Population: Full analysis set

Number and percentage of patients with at least one post randomisation asthma exacerbation.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Number and Percentage of Patients With ≥1 Asthma Exacerbation	19 Participants	17 Participants	39 Participants

SECONDARY outcome

Timeframe: The time from randomisation to the date of first asthma exacerbation over 28 weeks

Population: Full analysis set

Time to the first occurrence of asthma exacerbation post randomisation

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Time to the First Asthma Exacerbation	NA Days median survival time is not estimable due to number of exacerbations had not reached 50%.	NA Days median survival time is not estimable due to number of exacerbations had not reached 50%.	155 Days Interval 111.0 to Upper 95% CI for median is not estimable due to the curve representing the upper confidence limit of the survival function is above 50%

SECONDARY outcome

Timeframe: The time from randomisation to the date of first asthma exacerbation associated with hospitalization or ER over 28 weeks.

Population: Full analysis set

Time to the first exacerbation requiring hospitalization or ER visit post randomisation

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Time to the First Asthma Exacerbation Requiring Hospitalization or ER Visit	NA Days median survival time is not estimable due to number of exacerbations resulting hospitalization or ER visit had not reached 50%.	NA Days median survival time is not estimable due to number of exacerbations resulting hospitalization or ER visit had not reached 50%.	NA Days median survival time is not estimable due to number of exacerbations resulting hospitalization or ER visit had not reached 50%.

SECONDARY outcome

Timeframe: 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

Population: Full analysis set

The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator adjusted by the time of follow-up.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
The Annualized Rate of Asthma Exacerbation	0.83 events/year Interval 0.55 to 1.26	0.54 events/year Interval 0.34 to 0.88	1.83 events/year Interval 1.33 to 2.5

SECONDARY outcome

Timeframe: 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

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
The Annualized Rate of Asthma Exacerbations That Are Associated With an Emergency Room Visit or a Hospitalization	0.14 events/year Interval 0.05 to 0.38	0.02 events/year Interval 0.0 to 0.18	0.32 events/year Interval 0.16 to 0.65

SECONDARY outcome

Timeframe: 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

Population: Full analysis set

Number of days in hospital due to asthma, if none, 0 day is considered

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Number of Days in Hospital Due to Asthma	0.3 Days Standard Deviation 1.41 • Interval 0.02 to 0.19	0.5 Days Standard Deviation 3.86 • Interval 0.0 to 0.08	1.2 Days Standard Deviation 6.66 • Interval 0.04 to 0.35

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=68 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=68 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=73 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in Pre-bronchodilator FEV1	0.230 Liter Standard Deviation 0.429	0.255 Liter Standard Deviation 0.508	0.114 Liter Standard Deviation 0.401

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=68 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=67 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in Asthma Symptom Scores (Total)	-0.58 Scores on a scale Standard Deviation 1.03	-0.77 Scores on a scale Standard Deviation 1.03	-0.58 Scores on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=69 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=69 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in Asthma Symptom Scores (Daytime)	-0.32 Scores on a scale Standard Deviation 0.56	-0.44 Scores on a scale Standard Deviation 0.52	-0.32 Scores on a scale Standard Deviation 0.57

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=68 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=67 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in Asthma Symptom Scores (Nighttime)	-0.27 Scores on a scale Standard Deviation 0.51	-0.34 Scores on a scale Standard Deviation 0.54	-0.27 Scores on a scale Standard Deviation 0.54

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at 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. 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 \[number of day nebulizer times\].

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=68 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=67 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in Rescue Medication Use	-1.39 number of puffs per day Standard Deviation 2.86	-2.58 number of puffs per day Standard Deviation 4.36	-1.07 number of puffs per day Standard Deviation 2.86

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=68 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=67 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in Home Lung Function (Morning Peak Expiratory Flow)	32.697 Liter/min Standard Deviation 89.457	43.022 Liter/min Standard Deviation 73.303	10.884 Liter/min Standard Deviation 69.356

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=69 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=66 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in Home Lung Function (Evening Peak Expiratory Flow)	21.885 Liter/min Standard Deviation 83.136	34.157 Liter/min Standard Deviation 69.287	2.933 Liter/min Standard Deviation 72.302

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=68 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=67 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in the Proportion of Nights With Awakening Due to Asthma Requiring Rescue Medication	-0.158 Proportion Standard Deviation 0.283	-0.2 Proportion Standard Deviation 0.337	-0.186 Proportion Standard Deviation 0.344

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=66 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=66 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=67 Participants Placebo administered subcutaneously
Change From Baseline to Week 28 in ACQ-6	-0.86 Scores on a scale Standard Deviation 0.95	-1.09 Scores on a scale Standard Deviation 1.09	-0.68 Scores on a scale Standard Deviation 1.10

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
ACQ-6 Responders (Improvement) at Week 28	41 Participants 0.95	46 Participants 1.09	41 Participants 1.10

SECONDARY outcome

Timeframe: Change from baseline at week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=66 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=67 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=68 Participants Placebo administered subcutaneously
Change From Baseline at Week 28 in AQLQ(S)+12 (Overall)	0.90 Scores on a scale Standard Deviation 0.93	1.05 Scores on a scale Standard Deviation 1.04	0.67 Scores on a scale Standard Deviation 1.10

SECONDARY outcome

Timeframe: Week 28

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
AQLQ(s)+12 Responders (Improvement) at Week 28	43 Participants 0.95	44 Participants 1.09	39 Participants 1.10

SECONDARY outcome

Timeframe: From first dose to Week 24

Population: Safety analysis set

Duration of exposure from first dose date to last dose date.

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Extent of Exposure	162.53 Days Standard Deviation 30.09	159.77 Days Standard Deviation 35.781	167.05 Days Standard Deviation 10.697

SECONDARY outcome

Timeframe: Pre-first dose to Week 36

Population: PK analysis set

Pre-dose serum concentrations at each visit

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=71 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo Placebo administered subcutaneously
Serum Concentration of Benralizumab Baseline (n=69, 71)	NA ng/mL Geometric Coefficient of Variation NA Value is less than lower limit of quantification	NA ng/mL Geometric Coefficient of Variation NA Value is less than lower limit of quantification	—
Serum Concentration of Benralizumab Week 4 (n=67, 71)	804.37 ng/mL Geometric Coefficient of Variation 52.77	721.42 ng/mL Geometric Coefficient of Variation 52.30	—
Serum Concentration of Benralizumab week 8 (n=66, 69)	1152.96 ng/mL Geometric Coefficient of Variation 53.16	1019.65 ng/mL Geometric Coefficient of Variation 89.51	—
Serum Concentration of Benralizumab Week 12 (n=68, 67)	1319.14 ng/mL Geometric Coefficient of Variation 66.05	1057.91 ng/mL Geometric Coefficient of Variation 125.74	—
Serum Concentration of Benralizumab Week 16 (n=67,67)	1337.98 ng/mL Geometric Coefficient of Variation 118.90	303.54 ng/mL Geometric Coefficient of Variation 144.53	—
Serum Concentration of Benralizumab Week 24 (n=65, 66)	1162.62 ng/mL Geometric Coefficient of Variation 151.35	185.17 ng/mL Geometric Coefficient of Variation 278.32	—
Serum Concentration of Benralizumab Week 28 (n=65, 65)	1125.96 ng/mL Geometric Coefficient of Variation 173.79	684.57 ng/mL Geometric Coefficient of Variation 205.67	—
Serum Concentration of Benralizumab Week 36 (n=2, 4)	11.11 ng/mL Geometric Coefficient of Variation 2140.87	5.92 ng/mL Geometric Coefficient of Variation 1230.68	—

SECONDARY outcome

Timeframe: From baseline to follow-up Week 36

Population: Safety analysis set

Number and percentage of patients in different ADA response categories

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=72 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=73 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 Participants Placebo administered subcutaneously
Anti-drug Antibody Response Positive at any visit	5 Participants	7 Participants	6 Participants
Anti-drug Antibody Response Baseline and Post-baseline Postive	0 Participants	0 Participants	3 Participants
Anti-drug Antibody Response Only post-baseline positive	5 Participants	6 Participants	3 Participants
Anti-drug Antibody Response Only baseline positive	0 Participants	1 Participants	0 Participants
Anti-drug Antibody Response Persistently positive	4 Participants	6 Participants	5 Participants
Anti-drug Antibody Response Transient positive	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Change from baseline at Week 28

Population: Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Percent change from baseline in blood eosinophil counts at week 28

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=63 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=62 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=66 Participants Placebo administered subcutaneously
Percent Change From Baseline in Blood Eosinophil Counts	-97.4 percent change Standard Deviation 12.93	-94.9 percent change Standard Deviation 16.54	45.5 percent change Standard Deviation 239.51

SECONDARY outcome

Timeframe: From baseline to Week 28

Population: Global Sputum Substudy

Change from baseline in total lung capacity

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=22 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=26 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=23 Participants Placebo administered subcutaneously
Total Lung Capacity Week 12 (n=17, 23, 17)	-0.02 Liter Standard Deviation 0.95	-0.07 Liter Standard Deviation 0.68	-0.30 Liter Standard Deviation 1.08
Total Lung Capacity Week 28 (n=14, 18, 15)	0.11 Liter Standard Deviation 1.31	-0.21 Liter Standard Deviation 0.70	-0.47 Liter Standard Deviation 1.47

SECONDARY outcome

Timeframe: From baseline to Week 28

Population: Global Sputum Substudy

Change from baseline in residual volume

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=22 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=26 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=23 Participants Placebo administered subcutaneously
Residual Volume Week 12 (n=17, 23, 17)	0.02 Liter Standard Deviation 1.00	-0.22 Liter Standard Deviation 0.74	-0.35 Liter Standard Deviation 1.03
Residual Volume Week 28 (n=14, 18, 15)	0.07 Liter Standard Deviation 1.34	-0.31 Liter Standard Deviation 0.71	-0.41 Liter Standard Deviation 1.27

SECONDARY outcome

Timeframe: From baseline to Week 28

Population: Global Sputum Substudy

Change from baseline in vital capacity

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=22 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=26 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=23 Participants Placebo administered subcutaneously
Vital Capacity Week 12 (n=17, 24, 18)	0.15 Liter Standard Deviation 0.80	0.18 Liter Standard Deviation 0.35	0.13 Liter Standard Deviation 0.89
Vital Capacity Week 28 (n=14, 18, 15)	0.15 Liter Standard Deviation 0.41	0.11 Liter Standard Deviation 0.48	-0.08 Liter Standard Deviation 0.41

SECONDARY outcome

Timeframe: From baseline to Week 28

Population: Global Sputum Substudy

Change from baseline in functional residual capacity

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=22 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=26 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=23 Participants Placebo administered subcutaneously
Functional Residual Capacity Week 12 (n=17,23, 18)	-0.05 Liter Standard Deviation 1.06	-0.09 Liter Standard Deviation 0.74	-0.38 Liter Standard Deviation 0.99
Functional Residual Capacity Week 28 (n=13,18, 15)	-0.15 Liter Standard Deviation 1.49	-0.26 Liter Standard Deviation 0.74	-0.43 Liter Standard Deviation 1.25

SECONDARY outcome

Timeframe: From baseline to Week 28

Population: Global Sputum Substudy

Change from baseline in inspiratory capacity

Outcome measures

Outcome measures
Measure	Benralizumab 30 mg q.4 Weeks n=22 Participants Benralizumab administered subcutaneously every 4 weeks	Benralizumab 30 mg q.8 Weeks n=26 Participants Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=23 Participants Placebo administered subcutaneously
Inspiratory Capacity Week 12 (n=17, 23, 17)	0.44 Liter Standard Deviation 1.22	0.14 Liter Standard Deviation 0.88	-0.01 Liter Standard Deviation 0.40
Inspiratory Capacity Week 28 (n=14, 17, 15)	0.52 Liter Standard Deviation 1.16	0.09 Liter Standard Deviation 1.01	-0.02 Liter Standard Deviation 0.40

Adverse Events

Benra 30 mg q.4 Weeks

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Benra 30 mg q.8 Weeks

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo

Serious events: 14 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Mitchell Goldman, Global Clinical Lead Benralizumab

AstraZeneca

Phone: +1 301 398 0323

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee ≥ 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Benra 30 mg q.4 Weeks n=72 participants at risk Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=73 participants at risk Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 participants at risk Placebo administered subcutaneously
Cardiac disorders Atrial fibrillation	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Cardiac disorders Atrial flutter	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.3% 1/75 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Cardiac disorders Cardiac failure acute	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Cardiac disorders Pericarditis	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.3% 1/75 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Gastrointestinal disorders Oesophagitis	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Gastrointestinal disorders Umbilical hernia	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
General disorders Adverse drug reaction	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Hepatobiliary disorders Gallbladder polyp	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Immune system disorders Hypersensitivity	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Atypical pneumonia	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.3% 1/75 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Chronic sinusitis	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.3% 1/75 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Colonic abscess	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.3% 1/75 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Influenza	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	2.7% 2/75 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Pneumonia	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	2.7% 2/73 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	4.0% 3/75 • Number of events 3 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Pneumonia staphylococcal	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.3% 1/75 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Urinary tract infection bacterial	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Urosepsis	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Nervous system disorders Presyncope	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Renal and urinary disorders Nephrolithiasis	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Respiratory, thoracic and mediastinal disorders Asthma	4.2% 3/72 • Number of events 3 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	5.3% 4/75 • Number of events 5 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.3% 1/75 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Respiratory, thoracic and mediastinal disorders Status asthmaticus	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	4.0% 3/75 • Number of events 3 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Skin and subcutaneous tissue disorders Dermatitis atopic	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/75 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)

Measure	Benra 30 mg q.4 Weeks n=72 participants at risk Benralizumab administered subcutaneously every 4 weeks	Benra 30 mg q.8 Weeks n=73 participants at risk Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	Placebo n=75 participants at risk Placebo administered subcutaneously
Ear and labyrinth disorders Vertigo	1.4% 1/72 • Number of events 5 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	4.1% 3/73 • Number of events 3 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	2.7% 2/75 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Gastrointestinal disorders Nausea	1.4% 1/72 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	4.0% 3/75 • Number of events 3 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Bronchitis	6.9% 5/72 • Number of events 7 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	11.0% 8/73 • Number of events 10 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	16.0% 12/75 • Number of events 13 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Influenza	4.2% 3/72 • Number of events 3 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	6.7% 5/75 • Number of events 5 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Nasopharyngitis	15.3% 11/72 • Number of events 13 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	16.4% 12/73 • Number of events 14 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	20.0% 15/75 • Number of events 17 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Oral candidiasis	0.00% 0/72 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	0.00% 0/73 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	5.3% 4/75 • Number of events 4 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Rhinitis	2.8% 2/72 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	8.2% 6/73 • Number of events 7 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	2.7% 2/75 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Sinusitis	6.9% 5/72 • Number of events 8 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	5.5% 4/73 • Number of events 5 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	10.7% 8/75 • Number of events 11 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Infections and infestations Upper respiratory tract infection	5.6% 4/72 • Number of events 7 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	6.8% 5/73 • Number of events 6 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	6.7% 5/75 • Number of events 7 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Musculoskeletal and connective tissue disorders Back pain	2.8% 2/72 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	2.7% 2/73 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	5.3% 4/75 • Number of events 5 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Nervous system disorders Headache	6.9% 5/72 • Number of events 7 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	8.2% 6/73 • Number of events 10 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	5.3% 4/75 • Number of events 4 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Respiratory, thoracic and mediastinal disorders Asthma	8.3% 6/72 • Number of events 11 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	18.7% 14/75 • Number of events 17 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Respiratory, thoracic and mediastinal disorders Cough	2.8% 2/72 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	5.3% 4/75 • Number of events 4 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.8% 2/72 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	1.4% 1/73 • Number of events 1 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	5.3% 4/75 • Number of events 4 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)
Vascular disorders Hypertension	2.8% 2/72 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	4.1% 3/73 • Number of events 3 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)	2.7% 2/75 • Number of events 2 • Include events occurred from the start of study treatment to the end of study (up to 36 weeks)