Asthma
Conditions
Keywords
Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases
Brief summary
The purpose of this study is to determine whether Benralizumab reduces the exacerbation rate in patients with a history of asthma exacerbations and uncontrolled asthma receiving ICS-LABA with or without oral corticosteroids and additional asthma controllers.
Interventions
BIOLOGICALBenralizumab
Benralizumab subcutaneously on study week 0 until study week 52 inclusive.
BIOLOGICALPlacebo
Placebo subcutaneously on study week 0 until study week 52 inclusive.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent prior to any study specific procedures 2. Female and male aged 12 to 75 years, inclusively, at the time of Visit 1 3. History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (\>250µg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1. 4. Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers. The ICS and LABA can be parts of a combination product or given by separate inhalers. The ICS dose must be greater than or equal to 500 μg/day fluticasone propionate dry powder formulation or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion.
Exclusion criteria
1. Clinically important pulmonary disease other than asthma (e.g. 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 (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome) 2. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, 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 * Influence the findings of the studies or their interpretations * Impede the patient's ability to complete the entire duration of study 3. 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 4. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 56. | The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 56. | — |
| Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL | Immediately following the first administration of study drug through Study Week 56. | — |
| Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 56. | Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better. |
| Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL | Immediately following the first administration of study drug through Study Week 56. | Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better. |
| Change in Asthma Rescue Medication Use | Immediately following the first administration of study drug through Study Week 56. | Change from Baseline to Week 56 in number of Rescue medication use (puffs/day) |
| Home Lung Function Assessments Based on PEF | Immediately following the first administration of study drug through Study Week 56. | Change from Baseline to Week 56 in Home lung function (morning and evening Peak expiratory flow \[PEF\]) |
| Proportion of Nights With Awakening Due to Asthma | Immediately following the first administration of study drug through Study Week 56. | Change from Baseline to Week 56 on Proportion of Nights with awakening due to asthma |
| Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 56. | ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of \<=0.75 indicates well-controlled asthma, scores between 0.75 to \<=1.5 indicate partly controlled asthma, and \>1.5 indicates not well controlled asthma. |
| Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL | Immediately following the first administration of study drug through Study Week 56. | ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of \<=0.75 indicates well-controlled asthma, scores between 0.75 to \<=1.5 indicate partly controlled asthma, and \>1.5 indicates not well controlled asthma. |
| Number of Patients With >=1 Asthma Exacerbation | Immediately following the first administration of study drug through Study Week 56 | — |
| Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL | Immediately following the first administration of study drug through Study Week 56. | The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF. |
| Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations | Immediately following the first administration of study drug through Study Week 56. | Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization (adjudicated) |
| Pharmacokinetics of Benralizumab | Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 60 | Mean PK Concentration at each visit |
| Immunogenicity of Benralizumab | Pre-treatment until end of follow-up | Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post-baseline assessments (with \>=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. |
| Extent of Exposure | Immediately following the first administration of study drug through Study Week 56 | Extent of exposure is defined as the duration of treatment in days |
| Mean Change From Baseline to Week 56 in AQLQ(S)+12 | Immediately following the first administration of study drug through Study Week 56 | AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of \>=0.5 are considered clinically meaningful. |
| Change From Baseline to Week 56 in EQ-5D-5L VAS | Immediately following the first administration of study drug through Study Week 56 | EQ-5D-5L VAS is to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state. |
| Mean Work Productivity Loss Due to Asthma | Immediately following the first administration of study drug through Study Week 56 | WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. This is only applicable to patients who were employed. |
| Mean Productivity Loss Due to Asthma in Classroom | Immediately following the first administration of study drug through Study Week 56 | WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable for patients who took classes. |
| Number of Participants That Utilized Health Care Resources | Immediately following the first administration of study drug through Study Week 56 | — |
| Patient and Clinician Assessment of Response to Treatment | Immediately following the first administration of study drug through Study Week 56 | CGIC (clinician global impression of change), and PGIC (patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using a 7-point rating scale, ranging from 1 (Very much Improved), to 7 (Very much Worse). This endpoint was added after the second protocol amendment, thus not all patients had data to be analyzed. |
| Time to First Asthma Exacerbation | Immediately following the first administration of study drug through Study Week 56 | — |
Countries
Argentina, Canada, Chile, Germany, Japan, Philippines, Poland, Romania, Sweden, Ukraine, United States
Participant flow
Pre-assignment details
2505 participants signed informed consent, 2181 entered screening/run-in period, 1306 participants were randomised to receive treatment with benralizumab 30 mg Q4W, Q8W, or placebo. Of the 1306 patients randomised, all (100.0%) received treatment with study drug.
Participants by arm
| Arm | Count |
|---|---|
| Benralizumab 30 mg q.4 Weeks Benralizumab administered subcutaneously every 4 weeks | 425 |
| Benralizumab 30 mg q.8 Weeks Benralizumab administered subcutaneously every 8 weeks | 441 |
| Placebo Placebo administered subcutaneously | 440 |
| Total | 1,306 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 3 | 4 |
| Overall Study | Death | 2 | 2 | 1 |
| Overall Study | Eligibility criteria not fulfilled | 2 | 0 | 2 |
| Overall Study | Lost to Follow-up | 5 | 8 | 6 |
| Overall Study | Other reasons | 5 | 9 | 4 |
| Overall Study | Severe non-compliance to protocol | 3 | 1 | 2 |
| Overall Study | Study specific withdrawal criteria | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 15 | 27 | 19 |
Baseline characteristics
| Characteristic | Benralizumab 30 mg q.4 Weeks | Benralizumab 30 mg q.8 Weeks | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 50.0 Years STANDARD_DEVIATION 13.6 | 49 Years STANDARD_DEVIATION 14.3 | 48.8 Years STANDARD_DEVIATION 15.1 | 49.2 Years STANDARD_DEVIATION 14.3 |
| Gender Female | 270 Participants | 273 Participants | 264 Participants | 807 Participants |
| Gender Male | 155 Participants | 168 Participants | 176 Participants | 499 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 244 / 438 | 232 / 428 | 264 / 440 |
| serious Total, serious adverse events | 46 / 438 | 41 / 428 | 61 / 440 |
Outcome results
Primary
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL | 0.6 Events/year |
| Benralizumab 30 mg q.8 Weeks | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL | 0.66 Events/year |
| Placebo | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL | 0.93 Events/year |
p-value: 0.00295% CI: [0.49, 0.85]Negative Binomial
p-value: 0.01995% CI: [0.54, 0.95]Negative Binomial
Secondary
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \<300/uL, High-dose ICS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL | 0.78 Events/year |
| Benralizumab 30 mg q.8 Weeks | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL | 0.73 Events/year |
| Placebo | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL | 1.21 Events/year |
p-value: 0.01595% CI: [0.45, 0.92]Negative Binomial
p-value: 0.00595% CI: [0.42, 0.86]Negative Binomial
Secondary
Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations
Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization (adjudicated)
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations | 0.04 Events/year |
| Benralizumab 30 mg q.8 Weeks | Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations | 0.05 Events/year |
| Placebo | Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations | 0.04 Events/year |
p-value: 0.83795% CI: [0.48, 1.82]negative binomial
p-value: 0.53895% CI: [0.64, 2.35]negative binomial
Secondary
Change From Baseline to Week 56 in EQ-5D-5L VAS
EQ-5D-5L VAS is to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Change From Baseline to Week 56 in EQ-5D-5L VAS | 13.8 Scores on a scale | Standard Deviation 21.52 |
| Benralizumab 30 mg q.8 Weeks | Change From Baseline to Week 56 in EQ-5D-5L VAS | 15.5 Scores on a scale | Standard Deviation 20.36 |
| Placebo | Change From Baseline to Week 56 in EQ-5D-5L VAS | 12.1 Scores on a scale | Standard Deviation 20.13 |
Secondary
Change in Asthma Rescue Medication Use
Change from Baseline to Week 56 in number of Rescue medication use (puffs/day)
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Change in Asthma Rescue Medication Use | -2.0 Puffs per day | Standard Deviation 3.64 |
| Benralizumab 30 mg q.8 Weeks | Change in Asthma Rescue Medication Use | -2.92 Puffs per day | Standard Deviation 3.6 |
| Placebo | Change in Asthma Rescue Medication Use | -2.65 Puffs per day | Standard Deviation 9.57 |
p-value: 0.60395% CI: [-0.58, 0.99]Mixed Models Analysis
p-value: 0.20995% CI: [-1.29, 0.28]Mixed Models Analysis
Secondary
Extent of Exposure
Extent of exposure is defined as the duration of treatment in days
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Safety analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Extent of Exposure | 344.14 Days | Standard Deviation 73.129 |
| Benralizumab 30 mg q.8 Weeks | Extent of Exposure | 331.64 Days | Standard Deviation 88.839 |
| Placebo | Extent of Exposure | 336.69 Days | Standard Deviation 82.148 |
Secondary
Home Lung Function Assessments Based on PEF
Change from Baseline to Week 56 in Home lung function (morning and evening Peak expiratory flow \[PEF\])
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Home Lung Function Assessments Based on PEF | Change at Week 56, Morning (n=194, 193, 197) | 41.745 L/min | Standard Deviation 78.534 |
| Benralizumab 30 mg q.4 Weeks | Home Lung Function Assessments Based on PEF | Change at Week 56, Evening (n=194, 192, 197) | 35.142 L/min | Standard Deviation 75.489 |
| Benralizumab 30 mg q.8 Weeks | Home Lung Function Assessments Based on PEF | Change at Week 56, Morning (n=194, 193, 197) | 43.375 L/min | Standard Deviation 91.865 |
| Benralizumab 30 mg q.8 Weeks | Home Lung Function Assessments Based on PEF | Change at Week 56, Evening (n=194, 192, 197) | 39.270 L/min | Standard Deviation 89.772 |
| Placebo | Home Lung Function Assessments Based on PEF | Change at Week 56, Morning (n=194, 193, 197) | 23.961 L/min | Standard Deviation 71.509 |
| Placebo | Home Lung Function Assessments Based on PEF | Change at Week 56, Evening (n=194, 192, 197) | 15.448 L/min | Standard Deviation 78.341 |
Comparison: Morning PEF Change from Baseline to Week 56p-value: 0.02995% CI: [1.59, 30.12]Mixed Models Analysis
Comparison: Morning PEF Change from Baseline to Week 56p-value: 0.03795% CI: [0.9, 29.64]Mixed Models Analysis
Comparison: Evening PEF Change from Baseline to Week 56p-value: 0.01895% CI: [3.07, 32]Mixed Models Analysis
Comparison: Evening PEF Change from Baseline to Week 56p-value: 0.00495% CI: [6.65, 35.79]Mixed Models Analysis
Secondary
Immunogenicity of Benralizumab
Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at \>=2 post-baseline assessments (with \>=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Time frame: Pre-treatment until end of follow-up
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Positive at any visit (n=438, 427, 440) | 63 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Base- and Post-baseline Postive (n=431, 414, 430) | 5 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Only post-baseline positive (n=431, 420, 436) | 55 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Persistently positive (n=431, 420, 436) | 44 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Transient positive (n=431, 420, 436) | 16 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Only baseline positive (n=438, 421, 434) | 3 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Only baseline positive (n=438, 421, 434) | 2 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Positive at any visit (n=438, 427, 440) | 64 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Persistently positive (n=431, 420, 436) | 42 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Transient positive (n=431, 420, 436) | 20 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Base- and Post-baseline Postive (n=431, 414, 430) | 5 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Only post-baseline positive (n=431, 420, 436) | 57 Participants |
| Placebo | Immunogenicity of Benralizumab | Base- and Post-baseline Postive (n=431, 414, 430) | 5 Participants |
| Placebo | Immunogenicity of Benralizumab | Only post-baseline positive (n=431, 420, 436) | 8 Participants |
| Placebo | Immunogenicity of Benralizumab | Only baseline positive (n=438, 421, 434) | 0 Participants |
| Placebo | Immunogenicity of Benralizumab | Persistently positive (n=431, 420, 436) | 7 Participants |
| Placebo | Immunogenicity of Benralizumab | Positive at any visit (n=438, 427, 440) | 13 Participants |
| Placebo | Immunogenicity of Benralizumab | Transient positive (n=431, 420, 436) | 6 Participants |
Secondary
Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL
Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \<300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL | -1.05 Scores on a scale | Standard Deviation 1.14 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL | -0.95 Scores on a scale | Standard Deviation 1.13 |
| Placebo | Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL | -0.88 Scores on a scale | Standard Deviation 1.12 |
p-value: 0.28795% CI: [-0.44, 0.13]Mixed Models Analysis
p-value: 0.96695% CI: [-0.28, 0.29]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL
Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL | -1.33 Scores on a scale | Standard Deviation 1.23 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL | -1.4 Scores on a scale | Standard Deviation 1.17 |
| Placebo | Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL | -1.2 Scores on a scale | Standard Deviation 1.19 |
p-value: 0.22495% CI: [-0.32, 0.07]Mixed Models Analysis
p-value: 0.01995% CI: [-0.43, -0.04]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL
ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of \<=0.75 indicates well-controlled asthma, scores between 0.75 to \<=1.5 indicate partly controlled asthma, and \>1.5 indicates not well controlled asthma.
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \<300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL | -1.22 Scores on a scale | Standard Deviation 1.16 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL | -1.06 Scores on a scale | Standard Deviation 1.02 |
| Placebo | Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL | -0.83 Scores on a scale | Standard Deviation 1.07 |
p-value: 0.07895% CI: [-0.51, 0.03]Mixed Models Analysis
p-value: 0.44995% CI: [-0.37, 0.16]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL
ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of \<=0.75 indicates well-controlled asthma, scores between 0.75 to \<=1.5 indicate partly controlled asthma, and \>1.5 indicates not well controlled asthma.
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL | -1.34 Scores on a scale | Standard Deviation 1.13 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL | -1.49 Scores on a scale | Standard Deviation 1.13 |
| Placebo | Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL | -1.21 Scores on a scale | Standard Deviation 1.12 |
p-value: 0.04395% CI: [-0.38, -0.01]Mixed Models Analysis
p-value: 0.00895% CI: [-0.44, -0.07]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 56 in AQLQ(S)+12
AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of \>=0.5 are considered clinically meaningful.
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 56 in AQLQ(S)+12 | 1.44 Scores on a scale | Standard Deviation 1.15 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 56 in AQLQ(S)+12 | 1.61 Scores on a scale | Standard Deviation 1.24 |
| Placebo | Mean Change From Baseline to Week 56 in AQLQ(S)+12 | 1.32 Scores on a scale | Standard Deviation 1.19 |
p-value: 0.11995% CI: [-0.04, 0.37]Mixed Models Analysis
p-value: 0.01995% CI: [0.04, 0.45]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \<300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL | 0.221 Liter | Standard Deviation 0.441 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL | 0.164 Liter | Standard Deviation 0.358 |
| Placebo | Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL | 0.135 Liter | Standard Deviation 0.437 |
p-value: 0.26895% CI: [-0.049, 0.176]Mixed Models Analysis
p-value: 0.78695% CI: [-0.127, 0.096]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL | 0.34 Liter | Standard Deviation 0.469 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL | 0.332 Liter | Standard Deviation 0.518 |
| Placebo | Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL | 0.206 Liter | Standard Deviation 0.471 |
p-value: 0.00595% CI: [0.037, 0.213]Mixed Models Analysis
p-value: 0.0195% CI: [0.028, 0.204]Mixed Models Analysis
Secondary
Mean Productivity Loss Due to Asthma in Classroom
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable for patients who took classes.
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS, who took classes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Productivity Loss Due to Asthma in Classroom | 19.92 percent of productivity loss | Standard Deviation 23.765 |
| Benralizumab 30 mg q.8 Weeks | Mean Productivity Loss Due to Asthma in Classroom | 14 percent of productivity loss | Standard Deviation 16.733 |
| Placebo | Mean Productivity Loss Due to Asthma in Classroom | 33.5 percent of productivity loss | Standard Deviation 25.593 |
Secondary
Mean Work Productivity Loss Due to Asthma
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. This is only applicable to patients who were employed.
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS, who were employed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Work Productivity Loss Due to Asthma | 26.56 Percent of productivity loss | Standard Deviation 25.589 |
| Benralizumab 30 mg q.8 Weeks | Mean Work Productivity Loss Due to Asthma | 24.44 Percent of productivity loss | Standard Deviation 24.689 |
| Placebo | Mean Work Productivity Loss Due to Asthma | 27.29 Percent of productivity loss | Standard Deviation 25.802 |
Secondary
Number of Participants That Utilized Health Care Resources
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Emergency department visits | 11 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Unscheduled outpatient visits | 72 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Home visits | 3 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Telephone calls | 50 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Ambulance transports | 2 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Hospitalizations | 11 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Hospitalizations | 14 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Emergency department visits | 12 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Telephone calls | 63 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Ambulance transports | 3 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Unscheduled outpatient visits | 75 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Home visits | 1 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Unscheduled outpatient visits | 83 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Home visits | 2 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Hospitalizations | 12 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Telephone calls | 58 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Emergency department visits | 18 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Ambulance transports | 5 Participants |
Secondary
Number of Patients With >=1 Asthma Exacerbation
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Number of Patients With >=1 Asthma Exacerbation | 84 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Patients With >=1 Asthma Exacerbation | 95 Participants |
| Placebo | Number of Patients With >=1 Asthma Exacerbation | 126 Participants |
Comparison: Proportion of patients with \>=1 asthma exacerbationp-value: <0.00195% CI: [0.31, 0.69]Cochran-Mantel-Haenszel
Comparison: Proportion of patients with \>=1 asthma exacerbationp-value: 0.02395% CI: [0.45, 0.95]Cochran-Mantel-Haenszel
Secondary
Patient and Clinician Assessment of Response to Treatment
CGIC (clinician global impression of change), and PGIC (patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using a 7-point rating scale, ranging from 1 (Very much Improved), to 7 (Very much Worse). This endpoint was added after the second protocol amendment, thus not all patients had data to be analyzed.
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Improved | 109 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Much Improved | 82 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Very Much Improved | 26 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Total | 217 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Improved | 109 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Much Improved | 83 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Very Much Improved | 34 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Total | 226 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Very Much Improved | 23 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Very Much Improved | 30 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Total | 190 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Improved | 95 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Total | 205 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | PGIC, Much Improved | 80 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Improved | 96 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician Assessment of Response to Treatment | CGIC, Much Improved | 71 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | CGIC, Much Improved | 65 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | PGIC, Total | 182 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | CGIC, Improved | 97 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | CGIC, Total | 176 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | PGIC, Very Much Improved | 17 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | PGIC, Much Improved | 66 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | PGIC, Improved | 99 Participants |
| Placebo | Patient and Clinician Assessment of Response to Treatment | CGIC, Very Much Improved | 14 Participants |
Secondary
Pharmacokinetics of Benralizumab
Mean PK Concentration at each visit
Time frame: Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 60
Population: PK analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Baseline (n=435, 419) | NA ng/mL | — |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 4 (n=430, 416) | 650.04 ng/mL | Geometric Coefficient of Variation 154.61 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 8 (n=414, 395) | 894.86 ng/mL | Geometric Coefficient of Variation 148.91 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 16 (n=390, 378) | 936.43 ng/mL | Geometric Coefficient of Variation 247.46 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 24 (n=388, 361) | 827.09 ng/mL | Geometric Coefficient of Variation 370.64 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 32 (n=345, 323) | 823.21 ng/mL | Geometric Coefficient of Variation 362.43 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 40 (n=370, 338) | 859.69 ng/mL | Geometric Coefficient of Variation 364.28 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 48 (n=355, 337) | 888.09 ng/mL | Geometric Coefficient of Variation 333.98 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 56 (n=358, 344) | 763.98 ng/mL | Geometric Coefficient of Variation 309.18 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 60 (n=49, 45) | 53.63 ng/mL | Geometric Coefficient of Variation 1782.96 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 48 (n=355, 337) | 186.5 ng/mL | Geometric Coefficient of Variation 290.28 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Baseline (n=435, 419) | NA ng/mL | — |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 32 (n=345, 323) | 166.53 ng/mL | Geometric Coefficient of Variation 289.34 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 4 (n=430, 416) | 703.16 ng/mL | Geometric Coefficient of Variation 89.48 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 60 (n=49, 45) | 18.63 ng/mL | Geometric Coefficient of Variation 756.47 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 8 (n=414, 395) | 939.45 ng/mL | Geometric Coefficient of Variation 98.99 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 40 (n=370, 338) | 172.28 ng/mL | Geometric Coefficient of Variation 298.6 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 16 (n=390, 378) | 252.54 ng/mL | Geometric Coefficient of Variation 274.74 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 56 (n=358, 344) | 173.41 ng/mL | Geometric Coefficient of Variation 235.86 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 24 (n=388, 361) | 188.99 ng/mL | Geometric Coefficient of Variation 308.38 |
Secondary
Proportion of Nights With Awakening Due to Asthma
Change from Baseline to Week 56 on Proportion of Nights with awakening due to asthma
Time frame: Immediately following the first administration of study drug through Study Week 56.
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Proportion of Nights With Awakening Due to Asthma | -0.373 Proportion of nights | Standard Deviation 0.388 |
| Benralizumab 30 mg q.8 Weeks | Proportion of Nights With Awakening Due to Asthma | -0.431 Proportion of nights | Standard Deviation 0.4 |
| Placebo | Proportion of Nights With Awakening Due to Asthma | -0.372 Proportion of nights | Standard Deviation 0.405 |
p-value: 0.495% CI: [-0.06, 0.03]Mixed Models Analysis
p-value: 0.14695% CI: [-0.08, 0.01]Mixed Models Analysis
Secondary
Time to First Asthma Exacerbation
Time frame: Immediately following the first administration of study drug through Study Week 56
Population: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Time to First Asthma Exacerbation | 84 Participants |
| Benralizumab 30 mg q.8 Weeks | Time to First Asthma Exacerbation | 95 Participants |
| Placebo | Time to First Asthma Exacerbation | 126 Participants |
Comparison: Time to first Exacerbationp-value: <0.00195% CI: [0.46, 0.8]Regression, Cox
Comparison: Time to first asthma exacerbationp-value: 0.01895% CI: [0.55, 0.95]Regression, Cox