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Efficacy and Safety Study of Benralizumab Added to High-dose Inhaled Corticosteroid Plus LABA in Patients With Uncontrolled Asthma

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ClinicalTrials.gov Identifier: NCT01928771
Recruitment Status : Completed
First Posted : August 27, 2013
Results First Posted : May 3, 2017
Last Update Posted : May 3, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Biological: Benralizumab
Biological: Placebo
Enrollment 2681
Recruitment Details  
Pre-assignment Details 2681 participants signed informed consent form, 2232 participants entered screening/run-in period,1205 participants were randomised to receive treatment with benralizumab 30 mg Q4W, Q8W, or placebo. Of the 1205 patients randomised, 1204 patients received treatment with the study drug.
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description Benralizumab administered every 4 weeks subcutaneously. Benralizumab administered every 8 weeks subcutaneously. Placebo administered subcutaneously
Period Title: Overall Study
Started 400 398 407
Received Treatment 399 398 407
Completed 354 358 367
Not Completed 46 40 40
Reason Not Completed
Adverse Event             6             5             1
Death             2             2             2
Lost to Follow-up             5             6             3
Withdrawal by Subject             20             15             17
Study-Specific Withdrawal Criteria             0             1             1
Other Reasons             9             9             14
Severe Non-Compliance to Protocol             4             2             2
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo Total
Hide Arm/Group Description Benralizumab administered every 4 weeks subcutaneously. Benralizumab administered every 8 weeks subcutaneously. Placebo administered subcutaneously Total of all reporting groups
Overall Number of Baseline Participants 399 398 407 1204
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 399 participants 398 participants 407 participants 1204 participants
50.1  (13.4) 47.6  (14.5) 48.7  (14.9) 48.8  (14.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 399 participants 398 participants 407 participants 1204 participants
Female
275
  68.9%
252
  63.3%
269
  66.1%
796
  66.1%
Male
124
  31.1%
146
  36.7%
138
  33.9%
408
  33.9%
1.Primary Outcome
Title Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils >=300/uL
Hide Description The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 275 267 267
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events/year
0.73
(0.60 to 0.89)
0.65
(0.53 to 0.80)
1.33
(1.12 to 1.58)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.42 to 0.71
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.37 to 0.64
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils < 300/uL
Hide Description The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils <300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 124 131 140
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events/year
0.85
(0.65 to 1.11)
1.00
(0.78 to 1.28)
1.21
(0.96 to 1.52)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.047
Comments [Not Specified]
Method Negative binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
0.5 to 1.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.268
Comments [Not Specified]
Method Negative binomial
Comments Model includes covariates treatment group, region, number of exacerbations in the previous year, and use of maintenance oral corticosteroids
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.59 to 1.16
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations
Hide Description The annual exacerbation rate associated with an emergency room visit or a hospitalization (adjudicated)
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 275 267 267
Least Squares Mean (95% Confidence Interval)
Unit of Measure: events/year
0.11
(0.07 to 0.16)
0.06
(0.04 to 0.11)
0.18
(0.13 to 0.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.053
Comments [Not Specified]
Method Negative binomial
Comments Model includes covariates treatment group, region, number of exacerbations resulting in ER/hospitalization in the previous year, and use of OCS
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.37 to 1.01
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Negative binomial
Comments Model includes covariates treatment group, region, number of exacerbations resulting in ER/hospitalization in the previous year, and use of OCS
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.2 to 0.67
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Patients With >=1 Asthma Exacerbations
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 275 267 267
Measure Type: Number
Unit of Measure: Participants
100 93 135
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Proportion of patients with >=1 asthma exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Controlling for region, number of exacerbations in the previous year, use of OCS
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.37 to 0.78
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Proportion of patients with >=1 asthma exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Controlling for region, number of exacerbations from the previous year, use of OCS
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.62
Confidence Interval (2-Sided) 95%
0.43 to 0.90
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to First Asthma Exacerbation
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 275 267 267
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
300 [2] 
(199 to NA)
[1]
Median time is not estimable due to less than 50% patients had exacerbations occurred.
[2]
Upper 95% CI for median is not estimable due to the curve representing the upper confidence limit of the survival function is above 50%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Time to first exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments Model includes treatment, number of exacerbations in the previous year, region, use of OCS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.49 to 0.82
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Time to first exacerbation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments Model includes treatment, number of exacerbations from the previous year, region, use of OCS
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.46 to 0.78
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinopiles >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 236 235 233
Mean (Standard Deviation)
Unit of Measure: Liter
0.353  (0.503) 0.398  (0.546) 0.237  (0.508)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.106
Confidence Interval (2-Sided) 95%
0.016 to 0.196
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.159
Confidence Interval (2-Sided) 95%
0.068 to 0.249
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinopiles <300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 105 119 125
Mean (Standard Deviation)
Unit of Measure: Liter
0.115  (0.417) 0.238  (0.483) 0.140  (0.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.644
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.025
Confidence Interval (2-Sided) 95%
-0.134 to 0.083
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.057
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline pre-BD FEV1, region, use of OCS, visit and treatment by visit
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.102
Confidence Interval (2-Sided) 95%
-0.003 to 0.208
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL
Hide 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 -10 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 Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 197 178 180
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.15  (1.31) -1.34  (1.27) -1.03  (1.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.442
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline asthma symptom score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.27 to 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline asthma symptom score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.45 to -0.06
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL
Hide 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 -10 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 Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils <300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 93 91 99
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-0.98  (1.19) -1.04  (1.24) -0.78  (0.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.169
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline asthma symptom score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.48 to 0.08
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.043
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline asthma symptom score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.57 to -0.01
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in Asthma Rescue Medication
Hide Description Change from baseline to week 48 in number of rescue medication use (puffs/day)
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 197 178 180
Mean (Standard Deviation)
Unit of Measure: Puffs/day
-2.74  (4.29) -2.78  (3.90) -2.18  (4.38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline asthma medication use, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.53
Confidence Interval (2-Sided) 95%
-1.16 to 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.081
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline asthma medication use, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-1.21 to 0.07
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Home Lung Function Assessment Based on Morning PEF
Hide Description Change from baseline to week 48 in home lung function morning peak expiratory flow [PEF]
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 205 181 189
Mean (Standard Deviation)
Unit of Measure: L/min
45.857  (84.227) 36.994  (72.002) 22.059  (74.434)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Morning PEF change from baseline to Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline morning PEF, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 23.32
Confidence Interval (2-Sided) 95%
9.20 to 37.43
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Morning PEF change from baseline to Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline morning PEF, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 16.46
Confidence Interval (2-Sided) 95%
2.08 to 30.83
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Home Lung Function Assessment Based on Evening PEF
Hide Description Change from baseline to week 48 in home lung function evening peak expiratory flow [PEF]
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 203 187 189
Mean (Standard Deviation)
Unit of Measure: L/min
36.806  (86.271) 33.460  (74.017) 14.784  (68.799)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments Evening PEF change from baseline to Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline evening PEF, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 21.75
Confidence Interval (2-Sided) 95%
7.86 to 35.65
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments Evening PEF change from baseline to Week 48
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline evening PEF, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 19.18
Confidence Interval (2-Sided) 95%
5.09 to 33.28
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Proportion of Night Awakening Due to Asthma
Hide Description Change from baseline to Week 48 on proportion of night awakening due to asthma
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 210 193 195
Mean (Standard Deviation)
Unit of Measure: Proportion of nights
-0.314  (0.366) -0.380  (0.385) -0.26  (0.344)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.964
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline proportion of nights with nocturnal awakenings, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.05 to 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline proportion of nights with nocturnal awakenings, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.11 to -0.01
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils >=300/uL
Hide 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 Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 198 191 186
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-1.33  (1.18) -1.47  (1.05) -1.12  (1.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.111
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.34 to 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.48 to -0.10
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils <300/uL
Hide 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 Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils <300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 89 94 97
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
-0.77  (1.07) -1.14  (1.11) -0.89  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.27 to 0.27
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.107
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes treatment, baseline ACQ-6 score, region, use of OCS, visit and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.48 to 0.05
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Pharmacokinetics of Benralizumab
Hide Description Mean PK concentrations at each visit
Time Frame Baseline, week 4, week 4 day 6, week 8, week 16, week 24, week 32, week 40, week 48, week 56
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 399 391 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Baseline (n=395, 386)
NA [1] 
(NA%)
NA [1] 
(NA%)
Week 4 (n=393, 375)
632.84
(152.14%)
629.89
(169.22%)
Week 4 day 6 (n=54, 63)
1368.98
(633.33%)
1273.7
(688.20%)
Week 8 (n=377, 366)
916.25
(142.53%)
881.57
(156.12%)
Week 16 (n=358, 350)
1024.26
(174.08%)
250.84
(228.25%)
Week 24 (n=349, 344)
926.62
(231.75%)
184.08
(298.92%)
Week 32 (n=260, 267)
853.67
(248.6%)
152.73
(394.18%)
Week 40 (n=328, 333)
967.15
(218.32%)
157.22
(364.6%)
Week 48 (n=333, 333)
864.37
(283.87%)
162.51
(352.46%)
Week 56 (n=63, 67)
51.7
(833.91%)
6.66
(321.88%)
[1]
Value is less than lower limit of quantification
17.Secondary Outcome
Title Immunogenicity of Benralizumab
Hide Description Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post baseline assessments (with >=16 weeks between the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Time Frame Pre-treatment until end of follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set, note that 4 patients who were randomized to q.8 regimen treated with q.4 regimen. Thus 403 patients treated with q.4 rather than 399, 394 patients treated with q.8 rather than 398. However, data were only available for 402 patients in q.4, and 393 patients in q.8.
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 402 393 407
Measure Type: Number
Unit of Measure: Participants
Positive at any visit (n=402, 393, 407) 47 58 21
Base- and post baseline positive (n=393, 381, 396) 2 3 10
Only post baseline positive (n=396, 389, 402) 39 49 10
Persistently positive (n=396, 389, 402) 23 39 16
Transiently positive (n=396, 389, 402) 18 13 4
Only baseline positive (n=399, 385, 401) 6 6 1
18.Secondary Outcome
Title Extend of Exposure
Hide Description Extend of exposure is defined as duration of treatment in days
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set, note that 4 patients who were randomized to q.8 regimen treated with q.4 regimen. Thus 403 patients treated with q.4 rather than 399, 394 patients treated with q.8 rather than 398.
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 403 394 407
Mean (Standard Deviation)
Unit of Measure: Days
285.86  (67.446) 288.02  (66.683) 289.38  (61.527)
19.Secondary Outcome
Title Mean Change From Baseline to Week 48 in AQLQ(S)+12
Hide 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 Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 192 187 180
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
1.44  (1.18) 1.56  (1.17) 1.25  (1.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.4 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.081
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes covariates treatment, baseline AQLQ(S)+12 score, region, use of OCS, visit, and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
-0.02 to 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg q.8 Weeks, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Mixed Models Analysis
Comments Model includes covariates treatment, baseline AQLQ(S)+12 score, region, use of OCS, visit, and visit by treatment
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
0.1 to 0.5
Estimation Comments [Not Specified]
20.Secondary Outcome
Title Mean Change From Baseline to Week 48 in EQ-5D-5L VAS
Hide Description EQ-5D-5L VAS is to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 191 186 181
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
13.5  (21.82) 16.5  (23.66) 12.5  (21.41)
21.Secondary Outcome
Title Mean Work Productivity Loss Due to Asthma
Hide Description WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. The work productivity loss is only applicable to patients who employed, which is only subset of the study population.
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL for patients who employed
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 85 79 76
Mean (Standard Deviation)
Unit of Measure: Percent of productivity loss
23.31  (24.169) 26.11  (23.06) 35.36  (24.537)
22.Secondary Outcome
Title Mean Productivity Loss Due to Asthma in Classroom
Hide Description WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable to patients who attending classes
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL who attending classes
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 8 6 18
Mean (Standard Deviation)
Unit of Measure: Percent of productivity loss
30.97  (25.311) 27.17  (38.456) 49.1  (25.801)
23.Secondary Outcome
Title Number of Participants That Utilized Health Care Resources
Hide Description [Not Specified]
Time Frame Immediately following the first administration of study drug through Study Week 48.
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300=/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 275 267 267
Measure Type: Number
Unit of Measure: Participants
Hospitalizations 14 12 20
Emergency department visits 20 10 26
Unscheduled outpatient visits 77 87 109
Home visits 2 1 3
Telephone calls 46 41 62
Ambulance transports 6 3 9
24.Secondary Outcome
Title Patient and Clinician's Responder Assessment to Treatment
Hide Description CGIC (Clinical global impression of change), and PGIC (Patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse). This is additional measures collected after second Amendment, thus not all patients had data to be analyzed.
Time Frame Immediately following the first administration of study drug through Study Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, Baseline eosinophils >=300/uL
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description:
Benralizumab administered every 4 weeks subcutaneously.
Benralizumab administered every 8 weeks subcutaneously.
Placebo administered subcutaneously
Overall Number of Participants Analyzed 275 267 267
Measure Type: Number
Unit of Measure: Participants
CGIC improved 80 76 88
CGIC much improved 59 58 58
CGIC very much improved 18 12 5
CGIC total responder 157 146 151
PGIC improved 84 80 91
PGIC much improved 55 58 65
PGIC very much improved 26 19 11
PGIC total responder 165 157 167
Time Frame [Not Specified]
Adverse Event Reporting Description There were 400 patients randomized to Benra q.4, and 398 patients randomized to Benra q.8. One patient in Benra q.4 was never treated. In addition, 4 patients who were randomized to q.8 group, but were treated with q.4 schedule. So 403 patients were treated with q.4 regimen, and 394 patients were treated with q.8 regimen.
 
Arm/Group Title Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Hide Arm/Group Description Benralizumab administered every 4 weeks subcutaneously. Benralizumab administered every 8 weeks subcutaneously. Placebo administered subcutaneously
All-Cause Mortality
Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   51/403 (12.66%)      54/394 (13.71%)      58/407 (14.25%)    
Blood and lymphatic system disorders       
Hypercoagulation  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Cardiac disorders       
Acute myocardial infarction  1  1/403 (0.25%)  1 0/394 (0.00%)  0 1/407 (0.25%)  1
Angina unstable  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Atrial fibrillation  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Cardiac failure  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Endocrine disorders       
Goitre  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Eye disorders       
Cataract  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Optic nerve disorder  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Gastrointestinal disorders       
Gastric ulcer  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Gastritis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Hiatus hernia  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Inguinal hernia  1  0/403 (0.00%)  0 1/394 (0.25%)  1 1/407 (0.25%)  1
Pancreatitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Upper gastrointestinal haemorrhage  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Volvulus  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
General disorders       
Chest pain  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Death  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Injection site erythema  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Oedema peripheral  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Sudden death  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Hepatobiliary disorders       
Cholecystitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Cholecystitis acute  1  2/403 (0.50%)  2 0/394 (0.00%)  0 1/407 (0.25%)  1
Immune system disorders       
Allergic granulomatous angiitis  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Contrast media allergy  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Infections and infestations       
Appendicitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Atypical pneumonia  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Bullous impetigo  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Cellulitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 1/407 (0.25%)  1
Chronic sinusitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Erysipelas  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Influenza  1  2/403 (0.50%)  2 0/394 (0.00%)  0 1/407 (0.25%)  1
Otitis media  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Parotitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Pneumonia  1  0/403 (0.00%)  0 2/394 (0.51%)  3 3/407 (0.74%)  3
Pneumonia bacterial  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Pneumonia pneumococcal  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Pneumonia viral  1  1/403 (0.25%)  1 1/394 (0.25%)  1 0/407 (0.00%)  0
Postoperative wound infection  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Pyelonephritis  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Sinusitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Urinary tract infection bacterial  1  0/403 (0.00%)  0 0/394 (0.00%)  0 2/407 (0.49%)  3
Urinary tract infection enterococcal  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Vestibular neuronitis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Viral infection  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Injury, poisoning and procedural complications       
Clavicle fracture  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Facial bones fracture  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Fall  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Femoral neck fracture  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Incisional hernia  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Ligament sprain  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  2
Lower limb fracture  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Lumbar vertebral fracture  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Muscle rupture  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Overdose  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Post procedural complication  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Procedural complication  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Procedural pain  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Rib fracture  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Tendon rupture  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Metabolism and nutrition disorders       
Diabetes mellitus  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Foot deformity  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Intervertebral disc degeneration  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Lumbar spinal stenosis  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Osteoarthritis  1  1/403 (0.25%)  1 0/394 (0.00%)  0 2/407 (0.49%)  2
Spinal osteoarthritis  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Vertebral foraminal stenosis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Adenolymphoma  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Colon adenoma  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Meningioma  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Ovarian epithelial cancer  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Nervous system disorders       
Aphonia  1  1/403 (0.25%)  2 0/394 (0.00%)  0 0/407 (0.00%)  0
Cerebral haemorrhage  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Cerebral venous thrombosis  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Paraesthesia  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  0/403 (0.00%)  0 1/394 (0.25%)  1 1/407 (0.25%)  1
Psychiatric disorders       
Anxiety  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Panic attack  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Renal and urinary disorders       
Nephrolithiasis  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Renal failure  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Reproductive system and breast disorders       
Endometriosis  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure  1  1/403 (0.25%)  2 0/394 (0.00%)  0 0/407 (0.00%)  0
Asthma  1  23/403 (5.71%)  29 24/394 (6.09%)  33 32/407 (7.86%)  42
Nasal polyps  1  2/403 (0.50%)  2 0/394 (0.00%)  0 1/407 (0.25%)  1
Pulmonary embolism  1  1/403 (0.25%)  1 0/394 (0.00%)  0 2/407 (0.49%)  2
Sinus polyp  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Skin and subcutaneous tissue disorders       
Dermatitis allergic  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Dermatitis atopic  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Erythema nodosum  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Rash papular  1  0/403 (0.00%)  0 1/394 (0.25%)  1 0/407 (0.00%)  0
Urticaria papular  1  1/403 (0.25%)  1 0/394 (0.00%)  0 0/407 (0.00%)  0
Vascular disorders       
Deep vein thrombosis  1  0/403 (0.00%)  0 0/394 (0.00%)  0 1/407 (0.25%)  1
Hypertension  1  0/403 (0.00%)  0 2/394 (0.51%)  2 0/407 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Benralizumab 30 mg q.4 Weeks Benralizumab 30 mg q.8 Weeks Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   214/403 (53.10%)      199/394 (50.51%)      219/407 (53.81%)    
Gastrointestinal disorders       
Nausea  1  8/403 (1.99%)  12 12/394 (3.05%)  14 8/407 (1.97%)  9
General disorders       
Pyrexia  1  16/403 (3.97%)  21 12/394 (3.05%)  19 8/407 (1.97%)  8
Infections and infestations       
Acute sinusitis  1  10/403 (2.48%)  11 13/394 (3.30%)  14 11/407 (2.70%)  15
Bronchitis  1  27/403 (6.70%)  28 19/394 (4.82%)  22 30/407 (7.37%)  41
Gastroenteritis  1  10/403 (2.48%)  16 12/394 (3.05%)  14 6/407 (1.47%)  6
Influenza  1  15/403 (3.72%)  19 19/394 (4.82%)  21 23/407 (5.65%)  31
Nasopharyngitis  1  47/403 (11.66%)  62 47/394 (11.93%)  69 49/407 (12.04%)  64
Pharyngitis  1  17/403 (4.22%)  21 23/394 (5.84%)  24 14/407 (3.44%)  20
Rhinitis  1  16/403 (3.97%)  17 10/394 (2.54%)  11 15/407 (3.69%)  17
Sinusitis  1  18/403 (4.47%)  23 22/394 (5.58%)  34 29/407 (7.13%)  43
Upper respiratory tract infection  1  45/403 (11.17%)  74 32/394 (8.12%)  51 37/407 (9.09%)  73
Musculoskeletal and connective tissue disorders       
Arthralgia  1  11/403 (2.73%)  13 18/394 (4.57%)  20 12/407 (2.95%)  19
Back pain  1  12/403 (2.98%)  13 8/394 (2.03%)  9 15/407 (3.69%)  15
Pain in extremity  1  3/403 (0.74%)  3 13/394 (3.30%)  13 5/407 (1.23%)  6
Nervous system disorders       
Headache  1  31/403 (7.69%)  38 37/394 (9.39%)  61 21/407 (5.16%)  28
Respiratory, thoracic and mediastinal disorders       
Asthma  1  48/403 (11.91%)  64 27/394 (6.85%)  38 60/407 (14.74%)  102
Cough  1  15/403 (3.72%)  17 13/394 (3.30%)  14 11/407 (2.70%)  15
Rhinitis allergic  1  11/403 (2.73%)  11 12/394 (3.05%)  12 8/407 (1.97%)  9
Indicates 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.
≥ 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Mitchell Goldman , Medical Science Director
Organization: AstraZeneca
Phone: +1 301 398 0323
EMail: Mitchell.Goldman@astrazeneca.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01928771     History of Changes
Other Study ID Numbers: D3250C00017
First Submitted: August 16, 2013
First Posted: August 27, 2013
Results First Submitted: September 28, 2016
Results First Posted: May 3, 2017
Last Update Posted: May 3, 2017