Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02322775
Recruitment Status : Completed
First Posted : December 23, 2014
Results First Posted : February 14, 2017
Last Update Posted : August 15, 2017
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Biological: Benralizumab
Biological: Placebo
Enrollment 211
Recruitment Details

After enrollment, eligible patients entered a 2- to 4-week screening/run-in period and were converted to budesonide dry powder inhaler twice daily for the duration of the study.

Patients who continued to meet eligibility criteria at the end of the run-in period entered a 12 weeks double-blind treatment period followed by two follow-up visits.

Pre-assignment Details Eligible adult patients were stratified by baseline blood eosinophil count (<300 cells/μL or ≥300 cells/μL) and by region (USA versus Rest of the World per the IVRS). Patients were then randomized to either benralizumab 30 mg Q4W or placebo in a 1:1 ratio.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description Benralizumab administered subcutaneously every 4 weeks Placebo administered subcutaneously every 4 weeks
Period Title: Overall Study
Started 106 105
Completed 101 99
Not Completed 5 6
Reason Not Completed
Adverse Event             1             0
Lost to Follow-up             0             1
Protocol Violation             1             0
Withdrawal by Subject             3             4
Not willing to perform all FU visits             0             1
Arm/Group Title Benralizumab 30 mg Q4W Placebo Total
Hide Arm/Group Description Benralizumab administered subcutaneously every 4 weeks Placebo administered subcutaneously every 4 weeks Total of all reporting groups
Overall Number of Baseline Participants 106 105 211
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 106 participants 105 participants 211 participants
48.3  (14.40) 51.1  (12.60) 49.7  (13.58)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
>=18-<50 years 49 44 93
>=50-<65 years 43 46 89
>=65-<=75 years 14 15 29
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
Female
62
  58.5%
67
  63.8%
129
  61.1%
Male
44
  41.5%
38
  36.2%
82
  38.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
Asian 1 0 1
Black or African American 7 4 11
White 98 99 197
Other 0 2 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 106 participants 105 participants 211 participants
Hispanic or Latino 6 3 9
Not Hispanic or Latino 100 102 202
1.Primary Outcome
Title Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12
Hide Description

The FEV1 (L) change from baseline are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect repeated measures (MMRM) analysis with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL), protocol specified visit (Week 4, Week 8, Week 12), region (Europe or North America) and treatment*visit interaction as fixed effects and baseline pre-bronchodilator FEV1 (L) as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline, Week 4, Week 8 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: Litre
Baseline 2.248  (0.6062) 2.246  (0.7677)
Week 12 2.310  (0.6702) 2.261  (0.7959)
Change from baseline at Week 12 0.057  (0.2734) -0.016  (0.2350)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments The null hypothesis was: H0: Change from baseline in pre-bronchodilator FEV1 (L) at Week 12 (benralizumab vs placebo)=0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
0 to 0.15
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Hide Description

The changes from baseline of weekly average of morning PEF (L/min) are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model for repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL), protocol specified visit, region (Europe or North America) and treatment*visit interaction as fixed effects and baseline morning PEF (L/min) as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: L/min
Baseline 307.413  (95.9467) 308.226  (113.5895)
Week 12 311.041  (101.8169) 304.037  (113.2538)
Change from baseline at Week 12 1.675  (56.5182) -6.196  (45.3077)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.233
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 8.84
Confidence Interval (2-Sided) 95%
-5.74 to 23.42
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Hide Description

The changes from baseline of weekly average of evening PEF (L/min) are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model for repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL), protocol specified visit, region (Europe or North America) and treatment*visit interaction as fixed effects and baseline evening PEF (L/min) as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: L/min
Baseline 326.948  (97.4034) 316.743  (116.6919)
Week 12 330.719  (106.7579) 316.047  (118.7000)
Change from baseline at Week 12 1.361  (51.9979) -2.956  (47.9136)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.456
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 5.29
Confidence Interval (2-Sided) 95%
-8.67 to 19.25
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Total Asthma Symptom Score at Week 12
Hide Description

Asthma symptoms were recorded by the patient each morning and evening in the asthma daily diary. Symptoms were recorded using a scale of 0-3, where 0 indicates no asthma symptoms. The daily asthma symptom total score was calculated by taking the sum of the daytime score recorded in the evening and the nighttime score recorded the following morning. The weekly total asthma score was averaged from the daily scores over a 7 day period, with score ranging from 0 to 6, where 0 indicates no asthma symptoms. The changes from baseline of weekly total asthma score are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL), protocol specified visit, region (Europe or North America) and treatment*visit interaction as fixed effects and baseline total asthma score as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline 1.934  (0.9310) 1.952  (1.0375)
Week 12 1.326  (1.0448) 1.541  (1.1208)
Change from baseline at Week 12 -0.567  (0.7875) -0.420  (0.8767)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.266
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.35 to 0.10
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12
Hide Description

The number of rescue medication inhalations and nebulizer treatments taken were recorded by the patient in the asthma daily diary twice daily. The number of inhalations (puffs) per day was calculated as [number of night inhaler puffs] + 2 x [number of night nebulizer times] + number of day inhaler puffs + 2 x [number of day nebulizer times]. The changes from baseline in weekly total asthma rescue medication use (puffs) are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL), protocol specified visit, region (Europe or North America) and treatment*visit interaction as fixed effects and baseline total asthma rescue medication use (puffs) as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: Puffs per day
Baseline 2.953  (3.0794) 2.641  (3.0671)
Week 12 1.647  (2.4782) 2.070  (2.6848)
Change from baseline at Week 12 -1.098  (2.3588) -0.665  (2.2744)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.200
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.91 to 0.19
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12
Hide Description

Nocturnal awakenings due to asthma symptoms and requiring rescue medication use was recorded by the patient in the asthma daily diary each morning. Proportion of nights with nocturnal awakenings was defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data for awakening due to asthma. The outcome variable for proportion of nights with nocturnal awakenings was the change from baseline at Week 12 in weekly proportion of nights with nocturnal awakenings. The changes are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect model repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL), protocol specified visit, region (Europe or North America) and treatment*visit interaction as fixed effects and baseline proportion of nights with nocturnal awakenings as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline, Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8, Week 9, Week 10, Week 11 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: Proportion of nights
Baseline 0.246  (0.2924) 0.279  (0.3326)
Week 12 0.086  (0.2003) 0.144  (0.2796)
Change from baseline at Week 12 -0.158  (0.2515) -0.139  (0.2659)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.380
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value -0.03
Confidence Interval (2-Sided) 95%
-0.08 to 0.03
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Mean ACQ-6 Score at Week 12
Hide Description

The asthma control questionnaire, ACQ-6, consists of six questions; all assessed on a 7-point scale from 0 to 6, where 0 represents good control and 6 represents poor control. The overall score is the mean of the responses to each of the six questions. The changes from baseline of ACQ-6 score are compared between benralizumab 30 mg Q4W and placebo by using the mixed-effect repeated measures (MMRM) with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL), protocol specified visit (Week 4, Week 8, Week 12), region (Europe or North America) and treatment*visit interaction as fixed effects and baseline ACQ-6 score as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline, Week 4, Week 8 and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Baseline 2.119  (0.8423) 2.092  (0.8975)
Week 12 1.428  (0.8621) 1.568  (1.0090)
Change from baseline at Week 12 -0.714  (0.8700) -0.495  (0.7908)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.114
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.39 to 0.04
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Asthma Exacerbations
Hide Description An asthma exacerbation was defined as a worsening of asthma that led to use of systemic corticosteroids for at least 3 days (a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids) or an emergency room or urgent care visit (defined as evaluation and treatment for <24 hours in an emergency department or urgent care center) due to asthma that required systemic corticosteroids (as per above) or an inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥24 hours) due to asthma. Number of patients experiencing an event included in the definition of asthma exacerbation was presented.
Time Frame Up to Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Measure Type: Number
Unit of Measure: Patients per number of exacerbations
0 exacerbation 105 103
1 exacerbation 0 2
2 exacerbations 1 0
9.Secondary Outcome
Title Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Hide Description

The asthma quality of life questionnaire for 12 years and older, AQLQ(S)+12, consists of 32 questions; all assessed on a 7-point scale from 7 to 1, where 7 represents no impairment and 1 represents severe impairment. The 4 individual domain scores (symptoms, activity limitations, emotional function, and environmental stimuli) are the means of the responses to the questions in each of the domains. The overall score is calculated as the mean response to all questions. The changes from baseline of AQLQ(S)+12 score are compared between benralizumab 30 mg Q4W and placebo by using the analyse of covariance (ANCOVA) with baseline blood eosinophil count (≥300 cells/μL or <300 cells/μL) and region (Europe or North America) as fixed effects and baseline AQLQ(S)+12 score as a covariate.

Changes at Week 12 were calculated based on patients with both baseline and Week 12.

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Total score - Baseline 4.825  (0.9787) 4.895  (1.0339)
Total score - W12 5.415  (0.9478) 5.284  (1.0851)
Total score - CFB at W12 0.585  (0.8675) 0.357  (0.7979)
Symptoms score - Baseline 4.649  (1.0367) 4.692  (1.0830)
Symptoms score - W12 5.380  (1.0076) 5.212  (1.1373)
Symptoms score - CFB at W12 0.727  (0.9890) 0.483  (0.9243)
Activity limitations score - Baseline 5.017  (1.0029) 5.048  (1.0277)
Activity limitations score - W12 5.503  (0.9672) 5.343  (1.0803)
Activity limitations score - CFB at W12 0.481  (0.8156) 0.275  (0.8105)
Emotional function score - Baseline 4.95  (1.277) 5.04  (1.373)
Emotional function score - W12 5.54  (1.215) 5.45  (1.307)
Emotional function score - CFB at W12 0.57  (1.094) 0.35  (1.014)
Environmental stimuli score - Baseline 4.658  (1.3320) 4.905  (1.3554)
Environmental stimuli score - W12 5.120  (1.2910) 5.130  (1.3372)
Environmental stimuli score - CFB at W12 0.466  (1.0135) 0.216  (0.9505)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments Parameter: Total score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0 to 0.42
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments Parameter: Symptoms score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
-0.01 to 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments Parameter: Activity limitation score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.061
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
-0.01 to 0.41
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments Parameter: Emotional function score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.156
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.07 to 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Benralizumab 30 mg Q4W, Placebo
Comments Parameter: Environmental stimuli score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.135
Comments Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square Means
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.06 to 0.44
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Serum Concentrations (ng/mL)
Hide Description Blood samples (processed to serum) for pharmacokinetic assessments were collected from all patients at baseline prior to first benralizumab administration at Day 1, at the Week 12 visit or the IP discontinuation visit, and at the Week 20 follow-up visit. Serum concentrations of benralizumab were determined using a validated electrochemiluminescent (ECL) immunoassay.
Time Frame Baseline, Week 12 and Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) analysis set comprised all patients who received benralizumab and from whom PK blood samples were obtained are assumed not to be affected by factors such as protocol violations. Those patients who had at least 1 quantifiable serum PK observation post first dose were included in the PK analysis dataset.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 103 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Pre- 1st dose
NA [1] 
(NA%)
Week 12
999.16
(95.53%)
Week 20
59.04
(317.71%)
[1]
All patients had concentration below the limit of quantification (3.86 ng/mL).
11.Secondary Outcome
Title Peripheral Blood Eosinophil Levels
Hide Description

Peripheral blood eosinophil levels assessments were collected from all patients at baseline prior to first benralizumab administration at Day 1, at the Week 12 visit or the IP discontinuation visit, and at the Week 20 follow-up visit.

Changes at Week 12 (respectively at Week 20) were calculated based on patients with both baseline and Week 12 (respectively Week 20).

Time Frame Baseline, Week 12 and Week 20
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set comprised all patients who received at least one dose of IP. Patients were classified according to the treatment they actually received. A patient who has on one or several occasions received active treatment was classified as active.
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description:
Benralizumab administered subcutaneously every 4 weeks
Placebo administered subcutaneously every 4 weeks
Overall Number of Participants Analyzed 106 105
Median (Full Range)
Unit of Measure: Cells/µL
Baseline
170
(30 to 1060)
220
(40 to 1140)
Week 12
0.00
(0 to 110)
230
(30 to 1000)
Change from baseline at Week 12
-170
(-1060 to 40)
10
(-710 to 910)
Week 20
0
(0 to 490)
210
(40 to 1440)
Change from Baseline at Week 20
-160
(-1060 to 130)
10
(-400 to 910)
Time Frame AEs, including SAEs, in the on-study period were defined as those with onset between day of the first dose of study treatment and last scheduled follow-up visit, inclusive, up to 20 weeks.
Adverse Event Reporting Description

The safety analysis set comprised all patients who received at least one dose of IP. Patients were classified according to the treatment they actually received. A patient who has on one or several occasions received active treatment was classified as active.

No subject received wrong dose in the study.

 
Arm/Group Title Benralizumab 30 mg Q4W Placebo
Hide Arm/Group Description Benralizumab administered subcutaneously every 4 weeks Placebo administered subcutaneously every 4 weeks
All-Cause Mortality
Benralizumab 30 mg Q4W Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Benralizumab 30 mg Q4W Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/106 (1.89%)      2/105 (1.90%)    
Blood and lymphatic system disorders     
Pancytopenia  1  1/106 (0.94%)  1 0/105 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cervix carcinoma  1  0/106 (0.00%)  0 1/105 (0.95%)  1
Colon adenoma  1  0/106 (0.00%)  0 1/105 (0.95%)  1
Psychiatric disorders     
Suicide attempt  1  1/106 (0.94%)  1 0/105 (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 Q4W Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/106 (17.92%)      14/105 (13.33%)    
Infections and infestations     
Nasopharyngitis  1  8/106 (7.55%)  8 8/105 (7.62%)  9
Upper respiratory tract infection  1  5/106 (4.72%)  5 5/105 (4.76%)  5
Nervous system disorders     
Headache  1  4/106 (3.77%)  7 1/105 (0.95%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  1  4/106 (3.77%)  4 3/105 (2.86%)  3
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, Global Clinical Leader Benralizumab
Organization: AstraZeneca Research and Development
Phone: 301 398 0323 ext +1
EMail: Mitchell.Goldman@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02322775     History of Changes
Other Study ID Numbers: D3250C00032
2014-004427-40 ( EudraCT Number )
First Submitted: December 19, 2014
First Posted: December 23, 2014
Results First Submitted: September 29, 2016
Results First Posted: February 14, 2017
Last Update Posted: August 15, 2017