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 number of asthma exacerbations in patients who remain uncontrolled on high doses of ICS-LABA.
Interventions
BIOLOGICALBenralizumab
Benralizumab subcutaneously on study week 0 until study week 44 inclusive.
BIOLOGICALPlacebo
Placebo subcutaneously on study week 0 until study week 44 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. Written informed consent for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent\[s\]/guardian\[s\]) and according to international guidelines and/or applicable European Union guidelines. 2. Female and Male aged 12 to 75 years inclusively, at the time of visit 1. For those patients, who are 17 on the day of Visit 1 but will turn 18 after this day, will be considered an adolescent for the purposes of this trial. 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. * For subjects 18 years of age and older, the ICS dose must be \>500 mcg/day fluticasone propionate dry powder formulation or equivalent daily. * For subjects ages 12-17, the ICS dose must be ≥500 mcg /day fluticasone propionate dry powder formulation or equivalent daily.
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 Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 48. | The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations | Immediately following the first administration of study drug through Study Week 48. | The annual exacerbation rate associated with an emergency room visit or a hospitalization (adjudicated) |
| Number of Patients With >=1 Asthma Exacerbations | Immediately following the first administration of study drug through Study Week 48. | — |
| Time to First Asthma Exacerbation | Immediately following the first administration of study drug through Study Week 48. | — |
| Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 48. | — |
| Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL | Immediately following the first administration of study drug through Study Week 48. | — |
| Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 48. | Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better. |
| Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL | Immediately following the first administration of study drug through Study Week 48. | Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better. |
| Change in Asthma Rescue Medication | Immediately following the first administration of study drug through Study Week 48. | Change from baseline to week 48 in number of rescue medication use (puffs/day) |
| Home Lung Function Assessment Based on Morning PEF | Immediately following the first administration of study drug through Study Week 48. | Change from baseline to week 48 in home lung function morning peak expiratory flow \[PEF\] |
| Home Lung Function Assessment Based on Evening PEF | Immediately following the first administration of study drug through Study Week 48. | Change from baseline to week 48 in home lung function evening peak expiratory flow \[PEF\] |
| Proportion of Night Awakening Due to Asthma | Immediately following the first administration of study drug through Study Week 48. | Change from baseline to Week 48 on proportion of night awakening due to asthma |
| Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils < 300/uL | Immediately following the first administration of study drug through Study Week 48. | The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF |
| Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils <300/uL | Immediately following the first administration of study drug through Study Week 48. | 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. |
| Pharmacokinetics of Benralizumab | Baseline, week 4, week 4 day 6, week 8, week 16, week 24, week 32, week 40, week 48, week 56 | Mean PK concentrations 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 the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive. |
| Extend of Exposure | Immediately following the first administration of study drug through Study Week 48. | Extend of exposure is defined as duration of treatment in days |
| Mean Change From Baseline to Week 48 in AQLQ(S)+12 | Immediately following the first administration of study drug through Study Week 48. | 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. |
| Mean Change From Baseline to Week 48 in EQ-5D-5L VAS | Immediately following the first administration of study drug through Study Week 48. | 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 48. | WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. The work productivity loss is only applicable to patients who employed, which is only subset of the study population. |
| Mean Productivity Loss Due to Asthma in Classroom | Immediately following the first administration of study drug through Study Week 48. | WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable to patients who attending classes |
| Number of Participants That Utilized Health Care Resources | Immediately following the first administration of study drug through Study Week 48. | — |
| Patient and Clinician's Responder Assessment to Treatment | Immediately following the first administration of study drug through Study Week 48 | CGIC (Clinical global impression of change), and PGIC (Patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse). This is additional measures collected after second Amendment, thus not all patients had data to be analyzed. |
| Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils >=300/uL | Immediately following the first administration of study drug through Study Week 48. | 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. |
Countries
Australia, Brazil, Bulgaria, Czechia, France, Italy, Mexico, Peru, Poland, Russia, South Africa, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States, Vietnam
Participant flow
Pre-assignment details
2681 participants signed informed consent form, 2232 participants entered screening/run-in period,1205 participants were randomised to receive treatment with benralizumab 30 mg Q4W, Q8W, or placebo. Of the 1205 patients randomised, 1204 patients received treatment with the study drug.
Participants by arm
| Arm | Count |
|---|---|
| Benralizumab 30 mg q.4 Weeks Benralizumab administered every 4 weeks subcutaneously. | 399 |
| Benralizumab 30 mg q.8 Weeks Benralizumab administered every 8 weeks subcutaneously. | 398 |
| Placebo Placebo administered subcutaneously | 407 |
| Total | 1,204 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 | 1 |
| Overall Study | Death | 2 | 2 | 2 |
| Overall Study | Lost to Follow-up | 5 | 6 | 3 |
| Overall Study | Other Reasons | 9 | 9 | 14 |
| Overall Study | Severe Non-Compliance to Protocol | 4 | 2 | 2 |
| Overall Study | Study-Specific Withdrawal Criteria | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 20 | 15 | 17 |
Baseline characteristics
| Characteristic | Benralizumab 30 mg q.4 Weeks | Benralizumab 30 mg q.8 Weeks | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 50.1 Years STANDARD_DEVIATION 13.4 | 47.6 Years STANDARD_DEVIATION 14.5 | 48.7 Years STANDARD_DEVIATION 14.9 | 48.8 Years STANDARD_DEVIATION 14.3 |
| Sex: Female, Male Female | 275 Participants | 252 Participants | 269 Participants | 796 Participants |
| Sex: Female, Male Male | 124 Participants | 146 Participants | 138 Participants | 408 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 | 214 / 403 | 199 / 394 | 219 / 407 |
| serious Total, serious adverse events | 51 / 403 | 54 / 394 | 58 / 407 |
Outcome results
Primary
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for 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 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| 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 Eosinophils >=300/uL | 0.73 events/year |
| Benralizumab 30 mg q.8 Weeks | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils >=300/uL | 0.65 events/year |
| Placebo | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils >=300/uL | 1.33 events/year |
p-value: <0.00195% CI: [0.42, 0.71]Negative binomial
p-value: <0.00195% CI: [0.37, 0.64]Negative binomial
Secondary
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for 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 48.
Population: Full analysis set, Baseline eosinophils \<300/uL
| 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 Eosinophils < 300/uL | 0.85 events/year |
| Benralizumab 30 mg q.8 Weeks | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils < 300/uL | 1.00 events/year |
| Placebo | Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils < 300/uL | 1.21 events/year |
p-value: 0.04795% CI: [0.5, 1]Negative binomial
p-value: 0.26895% CI: [0.59, 1.16]Negative binomial
Secondary
Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations
The annual exacerbation rate associated with an emergency room visit or a hospitalization (adjudicated)
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations | 0.11 events/year |
| Benralizumab 30 mg q.8 Weeks | Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations | 0.06 events/year |
| Placebo | Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations | 0.18 events/year |
p-value: 0.05395% CI: [0.37, 1.01]Negative binomial
p-value: <0.00195% CI: [0.2, 0.67]Negative binomial
Secondary
Change in Asthma Rescue Medication
Change from baseline to week 48 in number of rescue medication use (puffs/day)
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Change in Asthma Rescue Medication | -2.74 Puffs/day | Standard Deviation 4.29 |
| Benralizumab 30 mg q.8 Weeks | Change in Asthma Rescue Medication | -2.78 Puffs/day | Standard Deviation 3.9 |
| Placebo | Change in Asthma Rescue Medication | -2.18 Puffs/day | Standard Deviation 4.38 |
p-value: 0.195% CI: [-1.16, 0.1]Mixed Models Analysis
p-value: 0.08195% CI: [-1.21, 0.07]Mixed Models Analysis
Secondary
Extend of Exposure
Extend of exposure is defined as duration of treatment in days
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Safety analysis set, note that 4 patients who were randomized to q.8 regimen treated with q.4 regimen. Thus 403 patients treated with q.4 rather than 399, 394 patients treated with q.8 rather than 398.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Extend of Exposure | 285.86 Days | Standard Deviation 67.446 |
| Benralizumab 30 mg q.8 Weeks | Extend of Exposure | 288.02 Days | Standard Deviation 66.683 |
| Placebo | Extend of Exposure | 289.38 Days | Standard Deviation 61.527 |
Secondary
Home Lung Function Assessment Based on Evening PEF
Change from baseline to week 48 in home lung function evening peak expiratory flow \[PEF\]
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Home Lung Function Assessment Based on Evening PEF | 36.806 L/min | Standard Deviation 86.271 |
| Benralizumab 30 mg q.8 Weeks | Home Lung Function Assessment Based on Evening PEF | 33.460 L/min | Standard Deviation 74.017 |
| Placebo | Home Lung Function Assessment Based on Evening PEF | 14.784 L/min | Standard Deviation 68.799 |
Comparison: Evening PEF change from baseline to Week 48p-value: 0.00295% CI: [7.86, 35.65]Mixed Models Analysis
Comparison: Evening PEF change from baseline to Week 48p-value: 0.00895% CI: [5.09, 33.28]Mixed Models Analysis
Secondary
Home Lung Function Assessment Based on Morning PEF
Change from baseline to week 48 in home lung function morning peak expiratory flow \[PEF\]
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Home Lung Function Assessment Based on Morning PEF | 45.857 L/min | Standard Deviation 84.227 |
| Benralizumab 30 mg q.8 Weeks | Home Lung Function Assessment Based on Morning PEF | 36.994 L/min | Standard Deviation 72.002 |
| Placebo | Home Lung Function Assessment Based on Morning PEF | 22.059 L/min | Standard Deviation 74.434 |
Comparison: Morning PEF change from baseline to Week 48p-value: 0.00195% CI: [9.2, 37.43]Mixed Models Analysis
Comparison: Morning PEF change from baseline to Week 48p-value: 0.02595% CI: [2.08, 30.83]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 the first and the last positive) or positive at last post baseline assessment. Transiently positive is defined as having at least one post baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Time frame: Pre-treatment until end of follow-up
Population: Safety analysis set, note that 4 patients who were randomized to q.8 regimen treated with q.4 regimen. Thus 403 patients treated with q.4 rather than 399, 394 patients treated with q.8 rather than 398. However, data were only available for 402 patients in q.4, and 393 patients in q.8.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Only post baseline positive (n=396, 389, 402) | 39 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Only baseline positive (n=399, 385, 401) | 6 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Positive at any visit (n=402, 393, 407) | 47 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Transiently positive (n=396, 389, 402) | 18 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Persistently positive (n=396, 389, 402) | 23 Participants |
| Benralizumab 30 mg q.4 Weeks | Immunogenicity of Benralizumab | Base- and post baseline positive (n=393, 381, 396) | 2 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Persistently positive (n=396, 389, 402) | 39 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Only post baseline positive (n=396, 389, 402) | 49 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Only baseline positive (n=399, 385, 401) | 6 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Transiently positive (n=396, 389, 402) | 13 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Base- and post baseline positive (n=393, 381, 396) | 3 Participants |
| Benralizumab 30 mg q.8 Weeks | Immunogenicity of Benralizumab | Positive at any visit (n=402, 393, 407) | 58 Participants |
| Placebo | Immunogenicity of Benralizumab | Only baseline positive (n=399, 385, 401) | 1 Participants |
| Placebo | Immunogenicity of Benralizumab | Persistently positive (n=396, 389, 402) | 16 Participants |
| Placebo | Immunogenicity of Benralizumab | Transiently positive (n=396, 389, 402) | 4 Participants |
| Placebo | Immunogenicity of Benralizumab | Positive at any visit (n=402, 393, 407) | 21 Participants |
| Placebo | Immunogenicity of Benralizumab | Base- and post baseline positive (n=393, 381, 396) | 10 Participants |
| Placebo | Immunogenicity of Benralizumab | Only post baseline positive (n=396, 389, 402) | 10 Participants |
Secondary
Mean Change From Baseline to Week 48 in ACQ-6 for 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 48.
Population: Full analysis set, Baseline eosinophils \<300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils <300/uL | -0.77 Scores on a scale | Standard Deviation 1.07 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils <300/uL | -1.14 Scores on a scale | Standard Deviation 1.11 |
| Placebo | Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils <300/uL | -0.89 Scores on a scale | Standard Deviation 1.01 |
p-value: 0.9995% CI: [-0.27, 0.27]Mixed Models Analysis
p-value: 0.10795% CI: [-0.48, 0.05]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 48 in ACQ-6 for 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 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils >=300/uL | -1.33 Scores on a scale | Standard Deviation 1.18 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils >=300/uL | -1.47 Scores on a scale | Standard Deviation 1.05 |
| Placebo | Mean Change From Baseline to Week 48 in ACQ-6 for Baseline Eosinophils >=300/uL | -1.12 Scores on a scale | Standard Deviation 1.15 |
p-value: 0.11195% CI: [-0.34, 0.04]Mixed Models Analysis
p-value: 0.00395% CI: [-0.48, -0.1]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 48 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 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in AQLQ(S)+12 | 1.44 Scores on a scale | Standard Deviation 1.18 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in AQLQ(S)+12 | 1.56 Scores on a scale | Standard Deviation 1.17 |
| Placebo | Mean Change From Baseline to Week 48 in AQLQ(S)+12 | 1.25 Scores on a scale | Standard Deviation 1.18 |
p-value: 0.08195% CI: [-0.02, 0.37]Mixed Models Analysis
p-value: 0.00495% CI: [0.1, 0.5]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL
Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \<300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL | -0.98 Scores on a scale | Standard Deviation 1.19 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL | -1.04 Scores on a scale | Standard Deviation 1.24 |
| Placebo | Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils <300/uL | -0.78 Scores on a scale | Standard Deviation 0.99 |
p-value: 0.16995% CI: [-0.48, 0.08]Mixed Models Analysis
p-value: 0.04395% CI: [-0.57, -0.01]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL
Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL | -1.15 Scores on a scale | Standard Deviation 1.31 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL | -1.34 Scores on a scale | Standard Deviation 1.27 |
| Placebo | Mean Change From Baseline to Week 48 in Asthma Symptom Score for Baseline Eosinophils >=300/uL | -1.03 Scores on a scale | Standard Deviation 1.07 |
p-value: 0.44295% CI: [-0.27, 0.12]Mixed Models Analysis
p-value: 0.01295% CI: [-0.45, -0.06]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 48 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 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in EQ-5D-5L VAS | 13.5 Scores on a scale | Standard Deviation 21.82 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in EQ-5D-5L VAS | 16.5 Scores on a scale | Standard Deviation 23.66 |
| Placebo | Mean Change From Baseline to Week 48 in EQ-5D-5L VAS | 12.5 Scores on a scale | Standard Deviation 21.41 |
Secondary
Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinopiles \<300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL | 0.115 Liter | Standard Deviation 0.417 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL | 0.238 Liter | Standard Deviation 0.483 |
| Placebo | Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils <300/uL | 0.140 Liter | Standard Deviation 0.4 |
p-value: 0.64495% CI: [-0.134, 0.083]Mixed Models Analysis
p-value: 0.05795% CI: [-0.003, 0.208]Mixed Models Analysis
Secondary
Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinopiles \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL | 0.353 Liter | Standard Deviation 0.503 |
| Benralizumab 30 mg q.8 Weeks | Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL | 0.398 Liter | Standard Deviation 0.546 |
| Placebo | Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL | 0.237 Liter | Standard Deviation 0.508 |
p-value: 0.02295% CI: [0.016, 0.196]Mixed Models Analysis
p-value: 0.00195% CI: [0.068, 0.249]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 to patients who attending classes
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL who attending classes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Productivity Loss Due to Asthma in Classroom | 30.97 Percent of productivity loss | Standard Deviation 25.311 |
| Benralizumab 30 mg q.8 Weeks | Mean Productivity Loss Due to Asthma in Classroom | 27.17 Percent of productivity loss | Standard Deviation 38.456 |
| Placebo | Mean Productivity Loss Due to Asthma in Classroom | 49.1 Percent of productivity loss | Standard Deviation 25.801 |
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. The work productivity loss is only applicable to patients who employed, which is only subset of the study population.
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL for patients who employed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Mean Work Productivity Loss Due to Asthma | 23.31 Percent of productivity loss | Standard Deviation 24.169 |
| Benralizumab 30 mg q.8 Weeks | Mean Work Productivity Loss Due to Asthma | 26.11 Percent of productivity loss | Standard Deviation 23.06 |
| Placebo | Mean Work Productivity Loss Due to Asthma | 35.36 Percent of productivity loss | Standard Deviation 24.537 |
Secondary
Number of Participants That Utilized Health Care Resources
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300=/uL
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Hospitalizations | 14 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Emergency department visits | 20 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Unscheduled outpatient visits | 77 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Home visits | 2 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Telephone calls | 46 Participants |
| Benralizumab 30 mg q.4 Weeks | Number of Participants That Utilized Health Care Resources | Ambulance transports | 6 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 | Hospitalizations | 12 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Home visits | 1 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Telephone calls | 41 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Emergency department visits | 10 Participants |
| Benralizumab 30 mg q.8 Weeks | Number of Participants That Utilized Health Care Resources | Unscheduled outpatient visits | 87 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Emergency department visits | 26 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Unscheduled outpatient visits | 109 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Ambulance transports | 9 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Home visits | 3 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Hospitalizations | 20 Participants |
| Placebo | Number of Participants That Utilized Health Care Resources | Telephone calls | 62 Participants |
Secondary
Number of Patients With >=1 Asthma Exacerbations
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (NUMBER) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Number of Patients With >=1 Asthma Exacerbations | 100 Participants | 84.227 |
| Benralizumab 30 mg q.8 Weeks | Number of Patients With >=1 Asthma Exacerbations | 93 Participants | 72.002 |
| Placebo | Number of Patients With >=1 Asthma Exacerbations | 135 Participants | 74.434 |
Comparison: Proportion of patients with \>=1 asthma exacerbationp-value: 0.0195% CI: [0.43, 0.9]Cochran-Mantel-Haenszel
Comparison: Proportion of patients with \>=1 asthma exacerbationp-value: <0.00195% CI: [0.37, 0.78]Cochran-Mantel-Haenszel
Secondary
Patient and Clinician's Responder Assessment to Treatment
CGIC (Clinical global impression of change), and PGIC (Patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using 7-point rating scale, ranging from 1 (very much improved), to 7 (very much worse). This is additional measures collected after second Amendment, thus not all patients had data to be analyzed.
Time frame: Immediately following the first administration of study drug through Study Week 48
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC much improved | 55 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC much improved | 59 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC very much improved | 26 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC very much improved | 18 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC total responder | 165 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC improved | 80 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC total responder | 157 Participants |
| Benralizumab 30 mg q.4 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC improved | 84 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC improved | 80 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC much improved | 58 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC total responder | 146 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC very much improved | 19 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC improved | 76 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC much improved | 58 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | PGIC total responder | 157 Participants |
| Benralizumab 30 mg q.8 Weeks | Patient and Clinician's Responder Assessment to Treatment | CGIC very much improved | 12 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | PGIC total responder | 167 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | CGIC much improved | 58 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | CGIC very much improved | 5 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | CGIC total responder | 151 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | PGIC improved | 91 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | PGIC much improved | 65 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | PGIC very much improved | 11 Participants |
| Placebo | Patient and Clinician's Responder Assessment to Treatment | CGIC improved | 88 Participants |
Secondary
Pharmacokinetics of Benralizumab
Mean PK concentrations at each visit
Time frame: Baseline, week 4, week 4 day 6, week 8, week 16, week 24, week 32, week 40, week 48, week 56
Population: PK analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 48 (n=333, 333) | 864.37 ng/mL | Geometric Coefficient of Variation 283.87 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 4 day 6 (n=54, 63) | 1368.98 ng/mL | Geometric Coefficient of Variation 633.33 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 8 (n=377, 366) | 916.25 ng/mL | Geometric Coefficient of Variation 142.53 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 16 (n=358, 350) | 1024.26 ng/mL | Geometric Coefficient of Variation 174.08 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 24 (n=349, 344) | 926.62 ng/mL | Geometric Coefficient of Variation 231.75 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 32 (n=260, 267) | 853.67 ng/mL | Geometric Coefficient of Variation 248.6 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 40 (n=328, 333) | 967.15 ng/mL | Geometric Coefficient of Variation 218.32 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 56 (n=63, 67) | 51.7 ng/mL | Geometric Coefficient of Variation 833.91 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Week 4 (n=393, 375) | 632.84 ng/mL | Geometric Coefficient of Variation 152.14 |
| Benralizumab 30 mg q.4 Weeks | Pharmacokinetics of Benralizumab | Baseline (n=395, 386) | NA ng/mL | — |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 56 (n=63, 67) | 6.66 ng/mL | Geometric Coefficient of Variation 321.88 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 4 (n=393, 375) | 629.89 ng/mL | Geometric Coefficient of Variation 169.22 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 32 (n=260, 267) | 152.73 ng/mL | Geometric Coefficient of Variation 394.18 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 4 day 6 (n=54, 63) | 1273.7 ng/mL | Geometric Coefficient of Variation 688.2 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Baseline (n=395, 386) | NA ng/mL | — |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 8 (n=377, 366) | 881.57 ng/mL | Geometric Coefficient of Variation 156.12 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 48 (n=333, 333) | 162.51 ng/mL | Geometric Coefficient of Variation 352.46 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 16 (n=358, 350) | 250.84 ng/mL | Geometric Coefficient of Variation 228.25 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 40 (n=328, 333) | 157.22 ng/mL | Geometric Coefficient of Variation 364.6 |
| Benralizumab 30 mg q.8 Weeks | Pharmacokinetics of Benralizumab | Week 24 (n=349, 344) | 184.08 ng/mL | Geometric Coefficient of Variation 298.92 |
Secondary
Proportion of Night Awakening Due to Asthma
Change from baseline to Week 48 on proportion of night awakening due to asthma
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Proportion of Night Awakening Due to Asthma | -0.314 Proportion of nights | Standard Deviation 0.366 |
| Benralizumab 30 mg q.8 Weeks | Proportion of Night Awakening Due to Asthma | -0.380 Proportion of nights | Standard Deviation 0.385 |
| Placebo | Proportion of Night Awakening Due to Asthma | -0.26 Proportion of nights | Standard Deviation 0.344 |
p-value: 0.96495% CI: [-0.05, 0.04]Mixed Models Analysis
p-value: 0.01295% CI: [-0.11, -0.01]Mixed Models Analysis
Secondary
Time to First Asthma Exacerbation
Time frame: Immediately following the first administration of study drug through Study Week 48.
Population: Full analysis set, Baseline eosinophils \>=300/uL
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Benralizumab 30 mg q.4 Weeks | Time to First Asthma Exacerbation | NA Days | 95% Confidence Interval 84.227 |
| Benralizumab 30 mg q.8 Weeks | Time to First Asthma Exacerbation | NA Days | 95% Confidence Interval 72.002 |
| Placebo | Time to First Asthma Exacerbation | 300 Days | 95% Confidence Interval 74.434 |
Comparison: Time to first exacerbationp-value: <0.00195% CI: [0.49, 0.82]Regression, Cox
Comparison: Time to first exacerbationp-value: <0.00195% CI: [0.46, 0.78]Regression, Cox