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CompletedNCT02322775Updated Aug 15, 2017Results posted

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

A Phase 3 interventional study of Benralizumab and Placebo in Asthma, sponsored by AstraZeneca. Completed at 57 sites in 6 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2017-08-15.

Sponsored by AstraZeneca · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
211
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The purpose of this trial is to confirm the safety and clinical benefit of benralizumab administration in asthma patients with mild to moderate persistent asthma in order to gain an understanding of the benefit/risk of benralizumab across the spectrum of asthma disease.

02

Conditions studied

  • Asthma

Browse trials for

Keywords

  • Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases,
03

In context

Asthma

3,921 studies on the registry are indexed under Asthma; 507 are open to participants now.

This study's enrollment of 211 is above the median of 83 across 2,752 interventional studies indexed under Asthma.

Browse Asthma studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

Written informed consent for study participation must be obtained prior to any study related procedures being performed and according to international guidelines and/or applicable European Union (EU) guidelines.

  • Female and male aged 18 to 75 years, inclusively, at the time of Visit 1.
  • Weight of ≥40 kg.
  • Evidence of asthma as documented by post-bronchodilator (post-BD) reversibility in FEV1 of ≥ 12% demonstrated at Visit 2.
  • Documented use of 1 of the following types of asthma therapy at time of informed consent: Low- to medium-dose ICS (ie, 100 to 500 μg fluticasone dry powder formulation equivalents total daily dose) with or without other controller medications, eg, an LTRA and/or theophylline or Low-dose ICS/LABA fixed combination therapy (eg, the lowest regular maintenance dose approved in the local country will meet this criterion)
  • Morning pre-bronchodilator (pre-BD) FEV1 of > 50% to ≤ 90% predicted at Visit 2.

Exclusion criteria

Exclusion Criteria:

  • Clinically important pulmonary disease other than asthma (eg, active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome).
  • Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
  • Affect the safety of the patient throughout the study
  • nfluence the findings of the studies or their interpretations,- Impede the patient's ability to complete the entire duration of study.
  • Known history of allergy or reaction to the investigational product formulation.
  • History of anaphylaxis to any biologic therapy.- History of Guillain-Barré syndrome.
  • A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.- Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period.
  • Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study.
  • Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll.
  • A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
  • History of cancer:
  • Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
  • Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
211 participants (actual)

Study arms

  • Experimental
    Arm A

    Benralizumab administered subcutaneously every 4 weeks

    Biological: Benralizumab

  • Experimental
    Arm B

    Placebo administered subcutaneously every 4 weeks

    Biological: Placebo

Interventions

  • BiologicalBenralizumab

    Benralizumab administered subcutaneously every 4 weeks

  • BiologicalPlacebo

    Placebo administered subcutaneously every 4 weeks

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12

    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

Secondary outcomes

  1. Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12

    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

  2. Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12

    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

  3. Change From Baseline in Total Asthma Symptom Score at Week 12

    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

  4. Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12

    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

  5. Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12

    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

  6. Change From Baseline in Mean ACQ-6 Score at Week 12

    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

  7. Asthma Exacerbations

    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

  8. Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12

    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

  9. Serum Concentrations (ng/mL)

    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

  10. Peripheral Blood Eosinophil Levels

    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

07

Results

Posted Feb 14, 2017

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.

Participant flow — Overall Study
MilestoneBenralizumab 30 mg Q4WPlacebo
Started106105
Completed10199
Not completed56
Withdrew: Adverse event10
Withdrew: Lost to follow-up01
Withdrew: Protocol violation10
Withdrew: Withdrawal by subject34
Withdrew: Not willing to perform all fu visits01

Outcome measures

PrimaryChange From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12

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
Reported as:
Mean · Litre
Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12
LitreBenralizumab 30 mg Q4WPlacebo
Baseline2.248 ± 0.60622.246 ± 0.7677
Week 122.310 ± 0.67022.261 ± 0.7959
Change from baseline at Week 120.057 ± 0.2734-0.016 ± 0.2350
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · Mixed Models Analysis · p = 0.040 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 0.08 · 95% CI 0 to 0.15
SecondaryChange From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12

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
Reported as:
Mean · L/min
Change From Baseline in Morning Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
L/minBenralizumab 30 mg Q4WPlacebo
Baseline307.413 ± 95.9467308.226 ± 113.5895
Week 12311.041 ± 101.8169304.037 ± 113.2538
Change from baseline at Week 121.675 ± 56.5182-6.196 ± 45.3077
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · Mixed Models Analysis · p = 0.233 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 8.84 · 95% CI -5.74 to 23.42
SecondaryChange From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12

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
Reported as:
Mean · L/min
Change From Baseline in Evening Peak Expiratory Flow (PEF) (L/Min) at Home at Week 12
L/minBenralizumab 30 mg Q4WPlacebo
Baseline326.948 ± 97.4034316.743 ± 116.6919
Week 12330.719 ± 106.7579316.047 ± 118.7000
Change from baseline at Week 121.361 ± 51.9979-2.956 ± 47.9136
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · Mixed Models Analysis · p = 0.456 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 5.29 · 95% CI -8.67 to 19.25
SecondaryChange From Baseline in Total Asthma Symptom Score at Week 12

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
Reported as:
Mean · Scores on a scale
Change From Baseline in Total Asthma Symptom Score at Week 12
Scores on a scaleBenralizumab 30 mg Q4WPlacebo
Baseline1.934 ± 0.93101.952 ± 1.0375
Week 121.326 ± 1.04481.541 ± 1.1208
Change from baseline at Week 12-0.567 ± 0.7875-0.420 ± 0.8767
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · Mixed Models Analysis · p = 0.266 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: -0.13 · 95% CI -0.35 to 0.10
SecondaryChange From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12

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
Reported as:
Mean · Puffs per day
Change From Baseline in Total Asthma Rescue Medication Use (Puffs) at Week 12
Puffs per dayBenralizumab 30 mg Q4WPlacebo
Baseline2.953 ± 3.07942.641 ± 3.0671
Week 121.647 ± 2.47822.070 ± 2.6848
Change from baseline at Week 12-1.098 ± 2.3588-0.665 ± 2.2744
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · Mixed Models Analysis · p = 0.200 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: -0.36 · 95% CI -0.91 to 0.19
SecondaryChange From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12

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
Reported as:
Mean · Proportion of nights
Change From Baseline in Proportion of Nights With Nocturnal Awakenings at Week 12
Proportion of nightsBenralizumab 30 mg Q4WPlacebo
Baseline0.246 ± 0.29240.279 ± 0.3326
Week 120.086 ± 0.20030.144 ± 0.2796
Change from baseline at Week 12-0.158 ± 0.2515-0.139 ± 0.2659
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · Mixed Models Analysis · p = 0.380 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: -0.03 · 95% CI -0.08 to 0.03
SecondaryChange From Baseline in Mean ACQ-6 Score at Week 12

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
Reported as:
Mean · Scores on a scale
Change From Baseline in Mean ACQ-6 Score at Week 12
Scores on a scaleBenralizumab 30 mg Q4WPlacebo
Baseline2.119 ± 0.84232.092 ± 0.8975
Week 121.428 ± 0.86211.568 ± 1.0090
Change from baseline at Week 12-0.714 ± 0.8700-0.495 ± 0.7908
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · Mixed Models Analysis · p = 0.114 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: -0.17 · 95% CI -0.39 to 0.04
SecondaryAsthma Exacerbations

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
Reported as:
Number · Patients per number of exacerbations
Asthma Exacerbations
Patients per number of exacerbationsBenralizumab 30 mg Q4WPlacebo
0 exacerbation105103
1 exacerbation02
2 exacerbations10
SecondaryChange From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12

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
Reported as:
Mean · Scores on a scale
Change From Baseline in AQLQ(S)+12 Total and Domain Scores at Week 12
Scores on a scaleBenralizumab 30 mg Q4WPlacebo
Total score - Baseline4.825 ± 0.97874.895 ± 1.0339
Total score - W125.415 ± 0.94785.284 ± 1.0851
Total score - CFB at W120.585 ± 0.86750.357 ± 0.7979
Symptoms score - Baseline4.649 ± 1.03674.692 ± 1.0830
Symptoms score - W125.380 ± 1.00765.212 ± 1.1373
Symptoms score - CFB at W120.727 ± 0.98900.483 ± 0.9243
Activity limitations score - Baseline5.017 ± 1.00295.048 ± 1.0277
Activity limitations score - W125.503 ± 0.96725.343 ± 1.0803
Activity limitations score - CFB at W120.481 ± 0.81560.275 ± 0.8105
Emotional function score - Baseline4.95 ± 1.2775.04 ± 1.373
Emotional function score - W125.54 ± 1.2155.45 ± 1.307
Emotional function score - CFB at W120.57 ± 1.0940.35 ± 1.014
Environmental stimuli score - Baseline4.658 ± 1.33204.905 ± 1.3554
Environmental stimuli score - W125.120 ± 1.29105.130 ± 1.3372
Environmental stimuli score - CFB at W120.466 ± 1.01350.216 ± 0.9505
Statistical analysis
  • Benralizumab 30 mg Q4W vs Placebo · ANCOVA · p = 0.055 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 0.21 · 95% CI 0 to 0.42
  • Benralizumab 30 mg Q4W vs Placebo · ANCOVA · p = 0.063 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 0.23 · 95% CI -0.01 to 0.47
  • Benralizumab 30 mg Q4W vs Placebo · ANCOVA · p = 0.061 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 0.20 · 95% CI -0.01 to 0.41
  • Benralizumab 30 mg Q4W vs Placebo · ANCOVA · p = 0.156 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 0.19 · 95% CI -0.07 to 0.45
  • Benralizumab 30 mg Q4W vs Placebo · ANCOVA · p = 0.135 (Hypothesis testing were reported using 2-sided 5% level tests with nominal p-values (i.e., not adjusted for multiplicity).) · Difference of least square means: 0.19 · 95% CI -0.06 to 0.44
SecondarySerum Concentrations (ng/mL)

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
Reported as:
Geometric mean · ng/mL
Serum Concentrations (ng/mL)
ng/mLBenralizumab 30 mg Q4WPlacebo
Pre- 1st doseNA ± NA—
Week 12999.16 ± 95.53—
Week 2059.04 ± 317.71—
SecondaryPeripheral Blood Eosinophil Levels

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
Reported as:
Median · Cells/µL
Peripheral Blood Eosinophil Levels
Cells/µLBenralizumab 30 mg Q4WPlacebo
Baseline170 (30 to 1060)220 (40 to 1140)
Week 120.00 (0 to 110)230 (30 to 1000)
Change from baseline at Week 12-170 (-1060 to 40)10 (-710 to 910)
Week 200 (0 to 490)210 (40 to 1440)
Change from Baseline at Week 20-160 (-1060 to 130)10 (-400 to 910)

Adverse events

Collected over 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.. Non-serious events are listed at a 3% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Benralizumab 30 mg Q4W—2/106 (1.9%)19/106 (17.9%)
Placebo—2/105 (1.9%)14/105 (13.3%)
Most frequent serious events
Most frequent serious events
EventBenralizumab 30 mg Q4WPlacebo
Cervix carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1061/105
Colon adenomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)0/1061/105
PancytopeniaBlood and lymphatic system disorders1/1060/105
Suicide attemptPsychiatric disorders1/1060/105
Most frequent other events
Most frequent other events
EventBenralizumab 30 mg Q4WPlacebo
NasopharyngitisInfections and infestations8/1068/105
Upper respiratory tract infectionInfections and infestations5/1065/105
HeadacheNervous system disorders4/1061/105
AsthmaRespiratory, thoracic and mediastinal disorders4/1063/105

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Benralizumab 30 mg Q4WPlaceboTotal
Mean48.3 ± 14.4051.1 ± 12.6049.7 ± 13.58
Age, Customized
Age, Customized(Participants)Benralizumab 30 mg Q4WPlaceboTotal
>=18-<50 years494493
>=50-<65 years434689
>=65-<=75 years141529
Sex: Female, Male
Sex: Female, Male(Participants)Benralizumab 30 mg Q4WPlaceboTotal
Female6267129
Male443882
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Benralizumab 30 mg Q4WPlaceboTotal
Asian101
Black or African American7411
White9899197
Other022
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Benralizumab 30 mg Q4WPlaceboTotal
Hispanic or Latino639
Not Hispanic or Latino100102202
08

Study locations

57 sites
  • Research Site
    Los Angeles, California 90048, United States
  • Research Site
    Rolling Hills Estates, California 90274, United States
  • Research Site
    Clearwater, Florida 33756, United States
  • Research Site
    Orlando, Florida 32825, United States
  • Research Site
    Blue Island, Illinois 60406, United States
  • Research Site
    Skillman, New Jersey 08558, United States
  • Research Site
    Charlotte, North Carolina 28207, United States
  • Research Site
    Monroe, North Carolina 28112, United States
  • Research Site
    Raleigh, North Carolina 27607, United States
  • Research Site
    Winston-Salem, North Carolina 27103, United States
  • Research Site
    Cincinnati, Ohio 45231, United States
  • Research Site
    Grove City, Ohio 43123, United States
  • Research Site
    Oklahoma City, Oklahoma 73103, United States
  • Research Site
    Medford, Oregon 97504, United States
  • Research Site
    Spartanburg, South Carolina 29303, United States
  • Research Site
    El Paso, Texas 79903, United States
  • Research Site
    San Antonio, Texas 78229, United States
  • Research Site
    Vancouver, British Columbia V5Z 1M9, Canada
  • Research Site
    Ajax, Ontario L1Z 0M1, Canada
  • Research Site
    Burlington, Ontario L7N 3V2, Canada
  • Research Site
    Hamilton, Ontario L9C 2Y6, Canada
  • Research Site
    Ottawa, Ontario K2H 8T5, Canada
  • Research Site
    Toronto, Ontario M9C 4Z5, Canada
  • Research Site
    St Charles Borromee, Quebec J6E 2B4, Canada
  • Research Site
    Trois Rivieres, Quebec G8T 7A1, Canada
  • Research Site
    Quebec, G1G 3Y8, Canada
  • Research Site
    Quebec, G1V 4G5, Canada
  • Research Site
    Bamberg, 96049, Germany
  • Research Site
    Berlin, 10787, Germany
  • Research Site
    Frankfurt/Main, 60389, Germany
  • Research Site
    Frankfurt, 60596, Germany
  • Research Site
    Hannover, 30173, Germany
  • Research Site
    Neu-Isenburg, 63263, Germany
  • Research Site
    Balassagyarmat, 2660, Hungary
  • Research Site
    Komárom, 2900, Hungary
  • Research Site
    Miskolc, 3529, Hungary
  • Research Site
    Pécs, 7626, Hungary
  • Research Site
    Pécs, 7635, Hungary
  • Research Site
    Százhalombatta, 2440, Hungary
  • Research Site
    Katowice, 40-954, Poland
  • Research Site
    Mrągowo, 11-700, Poland
  • Research Site
    Ostrów Wielkopolski, 63-400, Poland
  • Research Site
    Pabianice, 95-200, Poland
  • Research Site
    Poznań, 60-693, Poland
  • Research Site
    Poznań, 60-823, Poland
  • Research Site
    Tarnów, 33-100, Poland
  • Research Site
    Wrocław, 51-162, Poland
  • Research Site
    Wrocław, 53-301, Poland
  • Research Site
    Bratislava, 821 06, Slovakia
  • Research Site
    Bratislava, 851 01, Slovakia
  • Research Site
    Humenne, 066 01, Slovakia
  • Research Site
    Kosice, 040 01, Slovakia
  • Research Site
    Levice, 934 01, Slovakia
  • Research Site
    Poprad, 058 01, Slovakia
  • Research Site
    Presov, 081 81, Slovakia
  • Research Site
    Vrable, 952 01, Slovakia
  • Research Site
    Zilina, 010 01, Slovakia
09

References and documents

Publications

  • Ferguson GT, FitzGerald JM, Bleecker ER, Laviolette M, Bernstein D, LaForce C, Mansfield L, Barker P, Wu Y, Jison M, Goldman M; BISE Study Investigators. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2017 Jul;5(7):568-576. doi: 10.1016/S2213-2600(17)30190-X. Epub 2017 May 22. PubMed 28545978 ↗

Related links

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 15, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02322775
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Dec 23, 2014
Start date
Feb 2, 2015
Primary completion
Oct 7, 2015
Completion
Oct 7, 2015
Results posted
Feb 14, 2017
Last update
Aug 15, 2017

Study contacts

Gary T. Ferguson, M.D.,P.C.
principal investigator · Pulmonary Research Institute of Southeast Michigan

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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