Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma (NCT NCT02322775)
NCT ID: NCT02322775
Last Updated: 2017-08-15
Results Overview
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.
COMPLETED
PHASE3
211 participants
Baseline, Week 4, Week 8 and Week 12
2017-08-15
Participant Flow
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.
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.
Participant milestones
| Measure |
Benralizumab 30 mg Q4W
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Overall Study
STARTED
|
106
|
105
|
|
Overall Study
COMPLETED
|
101
|
99
|
|
Overall Study
NOT COMPLETED
|
5
|
6
|
Reasons for withdrawal
| Measure |
Benralizumab 30 mg Q4W
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
3
|
4
|
|
Overall Study
Not willing to perform all FU visits
|
0
|
1
|
Baseline Characteristics
Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma
Baseline characteristics by cohort
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
Total
n=211 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48.3 Years
STANDARD_DEVIATION 14.40 • n=5 Participants
|
51.1 Years
STANDARD_DEVIATION 12.60 • n=7 Participants
|
49.7 Years
STANDARD_DEVIATION 13.58 • n=5 Participants
|
|
Age, Customized
>=18-<50 years
|
49 Participants
n=5 Participants
|
44 Participants
n=7 Participants
|
93 Participants
n=5 Participants
|
|
Age, Customized
>=50-<65 years
|
43 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Age, Customized
>=65-<=75 years
|
14 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
62 Participants
n=5 Participants
|
67 Participants
n=7 Participants
|
129 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
7 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
98 Participants
n=5 Participants
|
99 Participants
n=7 Participants
|
197 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
6 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
100 Participants
n=5 Participants
|
102 Participants
n=7 Participants
|
202 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 4, Week 8 and Week 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12
Baseline
|
2.248 Litre
Standard Deviation 0.6062
|
2.246 Litre
Standard Deviation 0.7677
|
|
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12
Week 12
|
2.310 Litre
Standard Deviation 0.6702
|
2.261 Litre
Standard Deviation 0.7959
|
|
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12
Change from baseline at Week 12
|
0.057 Litre
Standard Deviation 0.2734
|
-0.016 Litre
Standard Deviation 0.2350
|
SECONDARY outcome
Timeframe: 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 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Baseline
|
307.413 L/min
Standard Deviation 95.9467
|
308.226 L/min
Standard Deviation 113.5895
|
|
Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Week 12
|
311.041 L/min
Standard Deviation 101.8169
|
304.037 L/min
Standard Deviation 113.2538
|
|
Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Change from baseline at Week 12
|
1.675 L/min
Standard Deviation 56.5182
|
-6.196 L/min
Standard Deviation 45.3077
|
SECONDARY outcome
Timeframe: 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 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Change from baseline at Week 12
|
1.361 L/min
Standard Deviation 51.9979
|
-2.956 L/min
Standard Deviation 47.9136
|
|
Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Baseline
|
326.948 L/min
Standard Deviation 97.4034
|
316.743 L/min
Standard Deviation 116.6919
|
|
Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
Week 12
|
330.719 L/min
Standard Deviation 106.7579
|
316.047 L/min
Standard Deviation 118.7000
|
SECONDARY outcome
Timeframe: 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 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in Total Asthma Symptom Score at Week 12
Baseline
|
1.934 Scores on a scale
Standard Deviation 0.9310
|
1.952 Scores on a scale
Standard Deviation 1.0375
|
|
Change From Baseline in Total Asthma Symptom Score at Week 12
Week 12
|
1.326 Scores on a scale
Standard Deviation 1.0448
|
1.541 Scores on a scale
Standard Deviation 1.1208
|
|
Change From Baseline in Total Asthma Symptom Score at Week 12
Change from baseline at Week 12
|
-0.567 Scores on a scale
Standard Deviation 0.7875
|
-0.420 Scores on a scale
Standard Deviation 0.8767
|
SECONDARY outcome
Timeframe: 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 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12
Baseline
|
2.953 Puffs per day
Standard Deviation 3.0794
|
2.641 Puffs per day
Standard Deviation 3.0671
|
|
Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12
Week 12
|
1.647 Puffs per day
Standard Deviation 2.4782
|
2.070 Puffs per day
Standard Deviation 2.6848
|
|
Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12
Change from baseline at Week 12
|
-1.098 Puffs per day
Standard Deviation 2.3588
|
-0.665 Puffs per day
Standard Deviation 2.2744
|
SECONDARY outcome
Timeframe: 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 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12
Baseline
|
0.246 Proportion of nights
Standard Deviation 0.2924
|
0.279 Proportion of nights
Standard Deviation 0.3326
|
|
Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12
Week 12
|
0.086 Proportion of nights
Standard Deviation 0.2003
|
0.144 Proportion of nights
Standard Deviation 0.2796
|
|
Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12
Change from baseline at Week 12
|
-0.158 Proportion of nights
Standard Deviation 0.2515
|
-0.139 Proportion of nights
Standard Deviation 0.2659
|
SECONDARY outcome
Timeframe: Baseline, Week 4, Week 8 and Week 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in Mean ACQ-6 Score at Week 12
Baseline
|
2.119 Scores on a scale
Standard Deviation 0.8423
|
2.092 Scores on a scale
Standard Deviation 0.8975
|
|
Change From Baseline in Mean ACQ-6 Score at Week 12
Week 12
|
1.428 Scores on a scale
Standard Deviation 0.8621
|
1.568 Scores on a scale
Standard Deviation 1.0090
|
|
Change From Baseline in Mean ACQ-6 Score at Week 12
Change from baseline at Week 12
|
-0.714 Scores on a scale
Standard Deviation 0.8700
|
-0.495 Scores on a scale
Standard Deviation 0.7908
|
SECONDARY outcome
Timeframe: Up to Week 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Asthma Exacerbations
0 exacerbation
|
105 Patients per number of exacerbations
|
103 Patients per number of exacerbations
|
|
Asthma Exacerbations
1 exacerbation
|
0 Patients per number of exacerbations
|
2 Patients per number of exacerbations
|
|
Asthma Exacerbations
2 exacerbations
|
1 Patients per number of exacerbations
|
0 Patients per number of exacerbations
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Total score - Baseline
|
4.825 Scores on a scale
Standard Deviation 0.9787
|
4.895 Scores on a scale
Standard Deviation 1.0339
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Total score - W12
|
5.415 Scores on a scale
Standard Deviation 0.9478
|
5.284 Scores on a scale
Standard Deviation 1.0851
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Total score - CFB at W12
|
0.585 Scores on a scale
Standard Deviation 0.8675
|
0.357 Scores on a scale
Standard Deviation 0.7979
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Symptoms score - Baseline
|
4.649 Scores on a scale
Standard Deviation 1.0367
|
4.692 Scores on a scale
Standard Deviation 1.0830
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Symptoms score - W12
|
5.380 Scores on a scale
Standard Deviation 1.0076
|
5.212 Scores on a scale
Standard Deviation 1.1373
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Symptoms score - CFB at W12
|
0.727 Scores on a scale
Standard Deviation 0.9890
|
0.483 Scores on a scale
Standard Deviation 0.9243
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Activity limitations score - Baseline
|
5.017 Scores on a scale
Standard Deviation 1.0029
|
5.048 Scores on a scale
Standard Deviation 1.0277
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Activity limitations score - W12
|
5.503 Scores on a scale
Standard Deviation 0.9672
|
5.343 Scores on a scale
Standard Deviation 1.0803
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Activity limitations score - CFB at W12
|
0.481 Scores on a scale
Standard Deviation 0.8156
|
0.275 Scores on a scale
Standard Deviation 0.8105
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Emotional function score - Baseline
|
4.95 Scores on a scale
Standard Deviation 1.277
|
5.04 Scores on a scale
Standard Deviation 1.373
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Emotional function score - W12
|
5.54 Scores on a scale
Standard Deviation 1.215
|
5.45 Scores on a scale
Standard Deviation 1.307
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Emotional function score - CFB at W12
|
0.57 Scores on a scale
Standard Deviation 1.094
|
0.35 Scores on a scale
Standard Deviation 1.014
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Environmental stimuli score - Baseline
|
4.658 Scores on a scale
Standard Deviation 1.3320
|
4.905 Scores on a scale
Standard Deviation 1.3554
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Environmental stimuli score - W12
|
5.120 Scores on a scale
Standard Deviation 1.2910
|
5.130 Scores on a scale
Standard Deviation 1.3372
|
|
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Environmental stimuli score - CFB at W12
|
0.466 Scores on a scale
Standard Deviation 1.0135
|
0.216 Scores on a scale
Standard Deviation 0.9505
|
SECONDARY outcome
Timeframe: Baseline, Week 12 and Week 20Population: 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.
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.
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=103 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Serum Concentrations (ng/mL)
Pre- 1st dose
|
NA ng/mL
Geometric Coefficient of Variation NA
All patients had concentration below the limit of quantification (3.86 ng/mL).
|
—
|
|
Serum Concentrations (ng/mL)
Week 12
|
999.16 ng/mL
Geometric Coefficient of Variation 95.53
|
—
|
|
Serum Concentrations (ng/mL)
Week 20
|
59.04 ng/mL
Geometric Coefficient of Variation 317.71
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 12 and Week 20Population: 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.
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).
Outcome measures
| Measure |
Benralizumab 30 mg Q4W
n=106 Participants
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 Participants
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Peripheral Blood Eosinophil Levels
Baseline
|
170 Cells/µL
Interval 30.0 to 1060.0
|
220 Cells/µL
Interval 40.0 to 1140.0
|
|
Peripheral Blood Eosinophil Levels
Week 12
|
0.00 Cells/µL
Interval 0.0 to 110.0
|
230 Cells/µL
Interval 30.0 to 1000.0
|
|
Peripheral Blood Eosinophil Levels
Change from baseline at Week 12
|
-170 Cells/µL
Interval -1060.0 to 40.0
|
10 Cells/µL
Interval -710.0 to 910.0
|
|
Peripheral Blood Eosinophil Levels
Week 20
|
0 Cells/µL
Interval 0.0 to 490.0
|
210 Cells/µL
Interval 40.0 to 1440.0
|
|
Peripheral Blood Eosinophil Levels
Change from Baseline at Week 20
|
-160 Cells/µL
Interval -1060.0 to 130.0
|
10 Cells/µL
Interval -400.0 to 910.0
|
Adverse Events
Benralizumab 30 mg Q4W
Placebo
Serious adverse events
| Measure |
Benralizumab 30 mg Q4W
n=106 participants at risk
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 participants at risk
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.94%
1/106 • Number of events 1 • 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.
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.
|
0.00%
0/105 • 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.
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma
|
0.00%
0/106 • 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.
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.
|
0.95%
1/105 • Number of events 1 • 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.
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon adenoma
|
0.00%
0/106 • 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.
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.
|
0.95%
1/105 • Number of events 1 • 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.
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.
|
|
Psychiatric disorders
Suicide attempt
|
0.94%
1/106 • Number of events 1 • 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.
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.
|
0.00%
0/105 • 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.
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.
|
Other adverse events
| Measure |
Benralizumab 30 mg Q4W
n=106 participants at risk
Benralizumab administered subcutaneously every 4 weeks
|
Placebo
n=105 participants at risk
Placebo administered subcutaneously every 4 weeks
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
7.5%
8/106 • Number of events 8 • 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.
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.
|
7.6%
8/105 • Number of events 9 • 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.
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.
|
|
Infections and infestations
Upper respiratory tract infection
|
4.7%
5/106 • Number of events 5 • 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.
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.
|
4.8%
5/105 • Number of events 5 • 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.
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.
|
|
Nervous system disorders
Headache
|
3.8%
4/106 • Number of events 7 • 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.
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.
|
0.95%
1/105 • Number of events 1 • 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.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
3.8%
4/106 • Number of events 4 • 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.
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.
|
2.9%
3/105 • Number of events 3 • 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.
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.
|
Additional Information
Mitchell Goldman, Global Clinical Leader Benralizumab
AstraZeneca Research and Development
Results disclosure agreements
- Principal investigator is a sponsor employee ≥ 60 days prior to submission of material for publication/presentation, Institution and PI shall jointly provide AZ with material for review. No publication/presentation may include any of AZ's Confidential Information without AZ's written approval. AZ can request Inst. and PI to withhold material from submission for publication/presentation for an additional 90 days to allow AZ to establish and preserve its proprietary rights in the material being submitted for publication or presentation.
- Publication restrictions are in place
Restriction type: OTHER