Asthma
Conditions
Keywords
Asthma, Benralizumab, MEDI-563
Brief summary
The primary objective of the study is to evaluate the effect of multiple-dose subcutaneous administrations of MEDI-563 on adults with uncontrolled asthma.
Detailed description
This is a Phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the efficacy and safety of multiple-dose (7 doses) subcutaneous administration of benralizumab (MEDI-563) in adult subjects with uncontrolled asthma.
Interventions
BIOLOGICALBenralizumab 2 mg
EOS+ participants received single benralizumab 2 milligram (mg) injection followed by a single placebo injection subcutaneously.
BIOLOGICALBenralizumab 20 mg
EOS+ participants received single benralizumab 20 mg injection followed by a single placebo injection subcutaneously.
BIOLOGICALBenralizumab 100 mg
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
OTHERPlacebo
EOS+ and EOS- participants received two placebo injections subcutaneously.
Sponsors
MedImmune Ltd
MedImmune LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 through 75 years at the time of screening * Adequate contraception from screening through end of trial * Weight of more than (\>) 45 kilogram (kg) but less than or equal to (\<=) 150 kg (\>100 pound \[lb\] but \<=330 lb) * History of physician-diagnosed asthma for at least 12 months prior to screening * Physician prescribed daily use of medium-dose or high-dose inhaled corticosteroid(s) (ICS) plus long-acting beta 2 agonist (LABA) for at least 12 months prior to screening * Willingness to switch to an ICS/LABA combination product * Dose of other asthma controller medications must be stable for at least 30 days prior to screening * At least 2 documented asthma exacerbations in the 12 months prior to screening that required use of a systemic corticosteroid burst * For subjects 65 years of age or older, a chest x-ray (CXR) or chest computed tomography (CT) that is normal for an asthmatic population * Ability and willingness to complete the study to Week 66, and if needed to Week 92.
Exclusion criteria
* Known history of allergy or reaction to any component of the investigational product formulation * History of anaphylaxis to any biologic therapy * Unexplained diarrhea within 30 days prior to screening or diagnosis of helminth parasitic infestation within 6 months prior to screening * Use of immunosuppressive medication within 3 months prior to screening. Chronic oral prednisone or equivalent up to 10 milligram (mg) daily or 20 mg every other day for asthma is allowed * Oral corticosteroid burst or short-acting systemic corticosteroid within 30 days prior to screening or during the screening/run-in period * Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 30 days prior to the screening or during the screening/run-in period * Receipt of immunoglobulin or blood products within 30 days prior to screening * Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to screening, whichever is longer * Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to screening, whichever is longer * Previously received MEDI-563 * Any clinically relevant abnormal findings in physical examination * Past history of clinically significant cardiac disease or any electrocardiogram (ECG) abnormality * Breastfeeding or lactating women * History of alcohol or drug abuse within 12 months prior to screening * History of any known primary immunodeficiency disorder * Positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol * A positive human immunodeficiency virus (HIV) test or subject taking antiretroviral medications * History of cigarette smoking more than or equal to (\>=) 10 pack-years or smoking within 12 months prior to screening. * Known exposure to inhaled occupational agents or fumes with an established diagnosis of occupational asthma * History of cancer, except for basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy \>=12 months prior to screening or other malignancies treated with apparent success with curative therapy \>=5 years prior to screening * Stable dose of allergy vaccination regimen for less than 30 days prior to screening * Subjects unable to demonstrate acceptable inhaler and peak flow meter techniques.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants | Week 1 up to Week 52 | The annual asthma exacerbation rate (AER) was calculated as the total number of observed exacerbations in each group up to week 52, divided by total duration of person-year follow-up in each group. An asthma exacerbation is defined as a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids (tablets, suspension or injection) for a duration of at least 3 days as outlined in the Asthma Action Plan provided to the participant by the investigator on Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss) | Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52 | — |
| Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD) | Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52 | — |
| Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants | Baseline up to Week 92 | Immunogenicity assessment included determination of anti-drug (benralizumab) antibodies in serum samples. ADA positive was defined as a titer \>=50 at any point in the study. It was observed at baseline and any visit during the study. |
| Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Baseline up to Week 52 | Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. ACQ-6 score was summarized together for all participants. |
| Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Baseline up to Week 52 | Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Baseline up to Week 52 | Total Nasal Symptoms Score (TNSS) is a 3-item questionnaire, the sum of nasal symptoms, namely, nasal obstruction (rhinorrhea), nasal congestion, and nasal itching/sneezing. Each symptom was rated on a scale from 0-3, with 0 representing no symptoms, 1 mild, 2 moderate, and 3 severe symptoms. TNSS score was a summation of the 3 individual nasal symptom. TNSS score could range from 0 to 9 where higher score indicates worsening. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Baseline up to Week 51-52 | Asthma Symptom Diary included 7 questions about the participant symptom and the overall impact of treatment on the disease during the study period. Mean scores of the 7 questions were calculated to identify asthma symptom-free days. Asthma Symptom Diary Scores were analyzed on a bi-weekly basis and compared to baseline scores. Overall symptom score=(daytime frequency score + daytime severity score + nighttime severity score)/3, where total score ranges from 0 to 9. Higher score represents worsening. Mean asthma symptom diary score were summarized together for all participants. Mean asthma symptom diary score were summarized together for all participants. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Dose Response in EOS+ Participants | Baseline up to Week 66 | — |
| Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Baseline and Week 52 | FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Baseline and Week 52 | Forced Vital Capacity (FVC) was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Baseline and Week 52 | The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed while sitting or standing prior to using any medication (if needed) for asthma. Home PEF was determined separately for morning and evening, and were averaged for each participant. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Baseline and Week 52 | AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). The AQLQ(S) responses were categorized as improvement (defined as change from baseline \>=0.5), no change (defined as change from baseline \>= -0.5 to less than \[\<\] 0.5), and worse (defined as change from baseline \< -0.5). Data was summarized by each treatment group. |
| Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Baseline and Week 52 | The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems). Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Baseline and Week 52 | The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ-5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Baseline up to Week 51-52 | Percentage of nocturnal awakening-free nights were analyzed on a bi-weekly basis and compared to baseline scores. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms. |
| Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline up to Week 51-52 | Participants were provided inhalers of the same dose (medium- or high-dose) inhaled corticosteroid (ICS) plus long-acting beta antagonist (LABA) combination product as baseline prophylactic medication and continued with same dose throughout the study. Rescue medications such as short-term beta2 agonists were used as first-line treatment for worsening asthma symptoms. Investigator prescribed additional short term asthma controller medications included additional ICS, theophylline, inhaled cromones or antimuscarinics; if asthma symptoms remained mild but not resolved. If asthma symptoms worsened, participants received an oral corticosteroid burst. All rescue medications use with prophylactic medication (+ prophylactic) and without prophylactic medication (- prophylactic) was recorded in asthma symptom dairy by participant. Rescue medication use was analyzed on a bi-weekly basis and compared to baseline scores. |
Countries
Argentina, Brazil, Bulgaria, Canada, Colombia, Mexico, Peru, Poland, Russia, United States
Participant flow
Pre-assignment details
Participants were stratified based on the protocol defined eosinophilic phenotype (EOS+ versus EOS-) and inhaled corticosteroid (ICS) use during a 3-week screening period. A total of 964 participants were screened out of which 609 were randomized in the study, and of which 606 participants received at least one dose of investigational product.
Participants by arm
| Arm | Count |
|---|---|
| Eosinophilic Phenotype (EOS+) Placebo EOS+ (defined as ELEN Index \[proprietary mathematical algorithm to predict sputum eosinophil's greater than or equal to 2 percent\] positive and/or FeNO \[fraction of exhaled nitric oxide\] greater than or equal to \[\>=\] 50 parts per billion \[ppb\]) participants received matching placebo subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40. | 80 |
| EOS+ Benralizumab, 2 mg EOS+ participants received benralizumab 2 milligram (mg) subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40. | 81 |
| EOS+ Benralizumab, 20 mg EOS+ participants received benralizumab 20 mg subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40. | 81 |
| EOS+ Benralizumab, 100 mg EOS+ participants received benralizumab 50 mg as two subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40. | 82 |
| Non-eosinophil Phenotype (EOS-) Placebo EOS- (defined as ELEN Index negative and FeNO \<50 ppb) participants received matching placebo subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40. | 142 |
| EOS- Benralizumab, 100 mg EOS- participants received benralizumab 50 mg as two subcutaneous injections every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40. | 140 |
| Total | 606 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Did not meet entry ACQ-6 criteria | 0 | 0 | 1 | 0 | 1 | 1 |
| Overall Study | Incorrect enrollment/randomization | 0 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Lack of compliance | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 2 | 3 | 1 | 1 | 2 |
| Overall Study | Personal problems | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Serious adverse event | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Strongyloides stercoralis antibodies + | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Subject moved out of state/area | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Subject traveled to Argentina by 1 year | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Unable to continue visits | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Unplanned surgery | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 5 | 4 | 8 | 10 | 9 |
Baseline characteristics
| Characteristic | Eosinophilic Phenotype (EOS+) Placebo | EOS+ Benralizumab, 2 mg | EOS+ Benralizumab, 20 mg | EOS+ Benralizumab, 100 mg | Non-eosinophil Phenotype (EOS-) Placebo | EOS- Benralizumab, 100 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.6 years STANDARD_DEVIATION 11.7 | 47.1 years STANDARD_DEVIATION 12.8 | 46.6 years STANDARD_DEVIATION 13.2 | 47.8 years STANDARD_DEVIATION 12.9 | 50.0 years STANDARD_DEVIATION 12.3 | 50.0 years STANDARD_DEVIATION 11.5 | 48.3 years STANDARD_DEVIATION 12.4 |
| Sex: Female, Male Female | 53 Participants | 58 Participants | 48 Participants | 60 Participants | 100 Participants | 98 Participants | 417 Participants |
| Sex: Female, Male Male | 27 Participants | 23 Participants | 33 Participants | 22 Participants | 42 Participants | 42 Participants | 189 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 44 / 80 | 54 / 81 | 57 / 81 | 68 / 82 | 94 / 141 | 93 / 141 |
| serious Total, serious adverse events | 7 / 80 | 10 / 81 | 6 / 81 | 6 / 82 | 16 / 141 | 18 / 141 |
Outcome results
Primary
Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants
The annual asthma exacerbation rate (AER) was calculated as the total number of observed exacerbations in each group up to week 52, divided by total duration of person-year follow-up in each group. An asthma exacerbation is defined as a progressive increase of asthma symptoms (cough, wheeze, chest tightness, and/or shortness of breath) that does not resolve after the initiation of rescue medications and remains troublesome for the participant resulting in either 1) use of systemic corticosteroids or increase of a stable systemic maintenance dose for a duration of at least 3 days as prescribed or administered by the investigator or healthcare provider; or 2) participant initiation of systemic corticosteroids (tablets, suspension or injection) for a duration of at least 3 days as outlined in the Asthma Action Plan provided to the participant by the investigator on Day 1.
Time frame: Week 1 up to Week 52
Population: The modified intent-to-treat (mITT) population included all randomized participants who received any dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants | 0.57 AER events/person-year |
| EOS+ Benralizumab, 2 mg | Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants | 0.65 AER events/person-year |
| EOS+ Benralizumab, 20 mg | Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants | 0.37 AER events/person-year |
| EOS+ Benralizumab, 100 mg | Annual Asthma Exacerbation Rate (AER) for Eosinophilic Phenotype (EOS+) Participants | 0.34 AER events/person-year |
p-value: 0.78180% CI: [0.74, 1.59]Poisson Regression Method
p-value: 0.17380% CI: [0.42, 0.97]Poisson Regression Method
p-value: 0.09680% CI: [0.4, 0.89]Poisson Regression Method
Secondary
Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52
Asthma Control Questionnaire (ACQ) is a participant-reported questionnaire to assess the asthma control with 6 items assessing night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item was rated on a 7-point Likert scale ranging from 0 (no impairment) to 6 (maximum impairment). Overall ACQ score was the mean of the 6 item scores with a score range of 0 (well controlled) to 6 (extremely poor controlled). Data collected on Day 1 prior to dosing was considered as baseline. Results were reported for overall ACQ score. ACQ-6 score was summarized together for all participants.
Time frame: Baseline up to Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Baseline (n=80,80,80,82,142,140) | 2.7479 units on a scale | Standard Deviation 0.9762 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Change at Week 52 (n=34,42,40,39,64,73) | -0.8922 units on a scale | Standard Deviation 1.1969 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Baseline (n=80,80,80,82,142,140) | 2.6479 units on a scale | Standard Deviation 0.9908 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Change at Week 52 (n=34,42,40,39,64,73) | -1.1032 units on a scale | Standard Deviation 1.1207 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Baseline (n=80,80,80,82,142,140) | 2.4750 units on a scale | Standard Deviation 0.9106 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Change at Week 52 (n=34,42,40,39,64,73) | -1.2500 units on a scale | Standard Deviation 1.2247 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Baseline (n=80,80,80,82,142,140) | 2.5346 units on a scale | Standard Deviation 0.9728 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Change at Week 52 (n=34,42,40,39,64,73) | -1.1239 units on a scale | Standard Deviation 1.2852 |
| EOS- Placebo | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Baseline (n=80,80,80,82,142,140) | 2.4742 units on a scale | Standard Deviation 0.8408 |
| EOS- Placebo | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Change at Week 52 (n=34,42,40,39,64,73) | -0.8418 units on a scale | Standard Deviation 1.1343 |
| EOS- Benralizumab, 100 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Baseline (n=80,80,80,82,142,140) | 2.6381 units on a scale | Standard Deviation 0.833 |
| EOS- Benralizumab, 100 mg | Change From Baseline in Asthma Control Questionnaire (6-items) (ACQ-6) Score at Week 52 | Change at Week 52 (n=34,42,40,39,64,73) | -1.1295 units on a scale | Standard Deviation 1.1301 |
p-value: 0.125ANCOVA
p-value: 0.074ANCOVA
p-value: 0.057ANCOVA
p-value: 0.01ANCOVA
Secondary
Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52
AQLQ: a 32-item questionnaire evaluating quality of life of participants with asthma including 4 domains (symptoms, activity limitations, emotional function, and environmental stimuli). Participants were asked to recall their experiences during the previous 2 weeks and to score each of the 32 questions on a 7-point scale ranging from 7 (no impairment) to 1 (severe impairment). The overall score was calculated as the mean response to all questions. The 4 domain scores were the means of the responses to the questions in each of the domains. Overall AQLQ score and 4 domain scores ranged from 7 (no impairment) to 1 (severe impairment). The AQLQ(S) responses were categorized as improvement (defined as change from baseline \>=0.5), no change (defined as change from baseline \>= -0.5 to less than \[\<\] 0.5), and worse (defined as change from baseline \< -0.5). Data was summarized by each treatment group.
Time frame: Baseline and Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively. Data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Baseline (n=214,78,80,217) | 3.72 units on a scale | Standard Deviation 1.04 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Change at Week 52 (n=88,39,38,105) | 0.9634 units on a scale | Standard Deviation 1.3342 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Change at Week 52 (n=88,39,38,105) | 1.2612 units on a scale | Standard Deviation 1.2082 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Baseline (n=214,78,80,217) | 3.72 units on a scale | Standard Deviation 1.17 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Baseline (n=214,78,80,217) | 3.79 units on a scale | Standard Deviation 1.06 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Change at Week 52 (n=88,39,38,105) | 1.4474 units on a scale | Standard Deviation 1.4262 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Baseline (n=214,78,80,217) | 3.72 units on a scale | Standard Deviation 1.01 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Asthma Quality of Life Questionnaire (Standardized Version) (AQLQ[S]) Score at Week 52 | Change at Week 52 (n=88,39,38,105) | 1.1223 units on a scale | Standard Deviation 1.2636 |
p-value: 0.16880% CI: [0.017, 0.459]ANCOVA
p-value: 0.06980% CI: [0.121, 0.687]ANCOVA
p-value: 0.04980% CI: [0.163, 0.761]ANCOVA
Secondary
Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52
The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The EQ-5D VAS was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline and Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Baseline (n=213,79,74,208) | 65.0798 units on a scale | Standard Deviation 17.8903 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Change at Week 52 (n=148,58,53,161) | 12.8041 units on a scale | Standard Deviation 19.1036 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Change at Week 52 (n=148,58,53,161) | 12.5517 units on a scale | Standard Deviation 20.8008 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Baseline (n=213,79,74,208) | 65.4937 units on a scale | Standard Deviation 18.5063 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Baseline (n=213,79,74,208) | 64.3378 units on a scale | Standard Deviation 18.1427 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Change at Week 52 (n=148,58,53,161) | 15.4906 units on a scale | Standard Deviation 21.7297 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Baseline (n=213,79,74,208) | 64.6250 units on a scale | Standard Deviation 19.7778 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in EQ-5D Visual Analog Scale (VAS) at Week 52 | Change at Week 52 (n=148,58,53,161) | 13.7391 units on a scale | Standard Deviation 20.5139 |
p-value: 0.87180% CI: [-3.333, 2.586]ANCOVA
p-value: 0.22780% CI: [-0.175, 5.889]ANCOVA
p-value: 0.50380% CI: [-1.041, 3.319]ANCOVA
Secondary
Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52
The utility-based EQ-5D questionnaire comprises of two parts and provides a generic measure of health for clinical and economic appraisal. The health state valuation was the summary score of mobility, self-care, usual activities, pain/discomfort and anxiety/depression on a 3 category scale (no problem, moderate problem, severe problems). Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline and Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Baseline (n=213,79,74,209) | 0.7629 units on a scale | Standard Deviation 0.2153 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Change at Week 52 (n=148,58,53,161) | 0.0853 units on a scale | Standard Deviation 0.2096 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Change at Week 52 (n=148,58,53,161) | 0.0822 units on a scale | Standard Deviation 0.3137 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Baseline (n=213,79,74,209) | 0.7418 units on a scale | Standard Deviation 0.2376 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Baseline (n=213,79,74,209) | 0.7877 units on a scale | Standard Deviation 0.1878 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Change at Week 52 (n=148,58,53,161) | 0.1223 units on a scale | Standard Deviation 0.2132 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Baseline (n=213,79,74,209) | 0.7679 units on a scale | Standard Deviation 0.1623 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D) Health State Evaluation at Week 52 | Change at Week 52 (n=148,58,53,161) | 0.0824 units on a scale | Standard Deviation 0.2179 |
p-value: 0.5180% CI: [-0.058, 0.019]ANCOVA
p-value: 0.11380% CI: [0.008, 0.074]ANCOVA
p-value: 0.59980% CI: [-0.016, 0.038]ANCOVA
Secondary
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52
FEV1 was the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline and Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Baseline (n=215,80,81,218) | 2.033 liters | Standard Deviation 0.669 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Change at Week 52 (n=150,51,58,160) | 0.0098 liters | Standard Deviation 0.3615 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Change at Week 52 (n=150,51,58,160) | 0.1631 liters | Standard Deviation 0.4691 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Baseline (n=215,80,81,218) | 1.978 liters | Standard Deviation 0.701 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Baseline (n=215,80,81,218) | 2.080 liters | Standard Deviation 0.751 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Change at Week 52 (n=150,51,58,160) | 0.1847 liters | Standard Deviation 0.5234 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Baseline (n=215,80,81,218) | 2.012 liters | Standard Deviation 0.672 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) at Week 52 | Change at Week 52 (n=150,51,58,160) | 0.0998 liters | Standard Deviation 0.3541 |
p-value: 0.01480% CI: [0.076, 0.237]ANCOVA
p-value: 0.00480% CI: [0.102, 0.266]ANCOVA
p-value: 0.02680% CI: [0.039, 0.143]ANCOVA
Secondary
Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52
Asthma Symptom Diary included 7 questions about the participant symptom and the overall impact of treatment on the disease during the study period. Mean scores of the 7 questions were calculated to identify asthma symptom-free days. Asthma Symptom Diary Scores were analyzed on a bi-weekly basis and compared to baseline scores. Overall symptom score=(daytime frequency score + daytime severity score + nighttime severity score)/3, where total score ranges from 0 to 9. Higher score represents worsening. Mean asthma symptom diary score were summarized together for all participants. Mean asthma symptom diary score were summarized together for all participants. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline up to Week 51-52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | -0.37 units on a scale | Standard Deviation 0.61 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Baseline (n=204,72,74,210) | 1.58 units on a scale | Standard Deviation 0.6 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Baseline (n=204,72,74,210) | 1.65 units on a scale | Standard Deviation 0.65 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | -0.56 units on a scale | Standard Deviation 0.76 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Baseline (n=204,72,74,210) | 1.60 units on a scale | Standard Deviation 0.61 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | -0.56 units on a scale | Standard Deviation 0.69 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | -0.53 units on a scale | Standard Deviation 0.67 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Asthma Symptom Diary Score at Week 51-52 | Baseline (n=204,72,74,210) | 1.60 units on a scale | Standard Deviation 0.62 |
p-value: 0.13180% CI: [-0.336, -0.028]ANCOVA
p-value: 0.12680% CI: [-0.317, -0.028]ANCOVA
p-value: 0.09780% CI: [-0.247, -0.032]ANCOVA
Secondary
Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52
Forced Vital Capacity (FVC) was the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline and Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Baseline (n=80,80,81,82,135,136) | 3.282 liters | Standard Deviation 1.03 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Change at Week 52 (n=51,51,58,59,99,101) | 0.029 liters | Standard Deviation 0.514 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Baseline (n=80,80,81,82,135,136) | 3.069 liters | Standard Deviation 0.957 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Change at Week 52 (n=51,51,58,59,99,101) | 0.129 liters | Standard Deviation 0.565 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Baseline (n=80,80,81,82,135,136) | 3.285 liters | Standard Deviation 1.028 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Change at Week 52 (n=51,51,58,59,99,101) | 0.190 liters | Standard Deviation 0.586 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Baseline (n=80,80,81,82,135,136) | 3.110 liters | Standard Deviation 0.851 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Change at Week 52 (n=51,51,58,59,99,101) | 0.166 liters | Standard Deviation 0.445 |
| EOS- Placebo | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Baseline (n=80,80,81,82,135,136) | 3.043 liters | Standard Deviation 0.864 |
| EOS- Placebo | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Change at Week 52 (n=51,51,58,59,99,101) | -0.030 liters | Standard Deviation 0.426 |
| EOS- Benralizumab, 100 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Baseline (n=80,80,81,82,135,136) | 3.126 liters | Standard Deviation 0.981 |
| EOS- Benralizumab, 100 mg | Change From Baseline in Mean Forced Vital Capacity (FVC) at Week 52 | Change at Week 52 (n=51,51,58,59,99,101) | 0.056 liters | Standard Deviation 0.371 |
p-value: 0.384ANCOVA
p-value: 0.092ANCOVA
p-value: 0.134ANCOVA
p-value: 0.129ANCOVA
Secondary
Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52
Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline up to Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Baseline (n=222,81,81,222) | 26.88 parts per billion | Standard Deviation 23.57 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Change at Week 52 (n=148,57,56,157) | 1.2523 parts per billion | Standard Deviation 16.02 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Change at Week 52 (n=148,57,56,157) | -3.2222 parts per billion | Standard Deviation 33.2543 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Baseline (n=222,81,81,222) | 39.52 parts per billion | Standard Deviation 32.67 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Baseline (n=222,81,81,222) | 40.79 parts per billion | Standard Deviation 31.03 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Change at Week 52 (n=148,57,56,157) | -6.1905 parts per billion | Standard Deviation 30.1103 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Baseline (n=222,81,81,222) | 26.68 parts per billion | Standard Deviation 23.1 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Fraction Exhaled Nitric Oxide (FeNO) at Week 52 | Change at Week 52 (n=148,57,56,157) | 1.4384 parts per billion | Standard Deviation 28.909 |
p-value: 0.896ANCOVA
p-value: 0.944ANCOVA
p-value: 0.667ANCOVA
Secondary
Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52
Total Nasal Symptoms Score (TNSS) is a 3-item questionnaire, the sum of nasal symptoms, namely, nasal obstruction (rhinorrhea), nasal congestion, and nasal itching/sneezing. Each symptom was rated on a scale from 0-3, with 0 representing no symptoms, 1 mild, 2 moderate, and 3 severe symptoms. TNSS score was a summation of the 3 individual nasal symptom. TNSS score could range from 0 to 9 where higher score indicates worsening. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline up to Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Baseline (n=71,27,25,81) | 4.3 units on a scale | Standard Deviation 2 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Change at Week 52 (n=89,39,39,106) | -0.4 units on a scale | Standard Deviation 2.9 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Change at Week 52 (n=89,39,39,106) | -0.8 units on a scale | Standard Deviation 2.01 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Baseline (n=71,27,25,81) | 4.8 units on a scale | Standard Deviation 2 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Baseline (n=71,27,25,81) | 5.3 units on a scale | Standard Deviation 1.8 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Change at Week 52 (n=89,39,39,106) | -1.0 units on a scale | Standard Deviation 2.96 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Baseline (n=71,27,25,81) | 4.4 units on a scale | Standard Deviation 2.1 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Mean Total Nasal Symptoms Score (TNSS) at Week 52 | Change at Week 52 (n=89,39,39,106) | -0.8 units on a scale | Standard Deviation 2.24 |
Secondary
Change From Baseline in Peak Expiratory Flow (PEF) at Week 52
The PEF is a participant's maximum speed of expiration, as measured with a peak flow meter. Peak flow testing for PEF was performed while sitting or standing prior to using any medication (if needed) for asthma. Home PEF was determined separately for morning and evening, and were averaged for each participant. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline and Week 52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Baseline (n=215,80,81,218) | 319.3 liters per minute | Standard Deviation 104.7 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Change at Week 52 (n=150,51,58,160) | 13.0 liters per minute | Standard Deviation 64.6 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Change at Week 52 (n=150,51,58,160) | 29.0 liters per minute | Standard Deviation 64.1 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Baseline (n=215,80,81,218) | 325.5 liters per minute | Standard Deviation 101.6 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Change at Week 52 (n=150,51,58,160) | 45.9 liters per minute | Standard Deviation 95.5 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Baseline (n=215,80,81,218) | 323.1 liters per minute | Standard Deviation 100.8 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Baseline (n=215,80,81,218) | 323.8 liters per minute | Standard Deviation 101.7 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Peak Expiratory Flow (PEF) at Week 52 | Change at Week 52 (n=150,51,58,160) | 26.6 liters per minute | Standard Deviation 66.3 |
Secondary
Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52
Percentage of nocturnal awakening-free nights were analyzed on a bi-weekly basis and compared to baseline scores. Data was summarized by each treatment group. In addition, data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
Time frame: Baseline up to Week 51-52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Baseline (n=204,72,74,210) | 52.05 percent nocturnal awakening-free nights | Standard Deviation 36.96 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | 19.7595 percent nocturnal awakening-free nights | Standard Deviation 39.1388 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | 27.1749 percent nocturnal awakening-free nights | Standard Deviation 41.7342 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Baseline (n=204,72,74,210) | 45.07 percent nocturnal awakening-free nights | Standard Deviation 40.04 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Baseline (n=204,72,74,210) | 51.57 percent nocturnal awakening-free nights | Standard Deviation 39.72 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | 29.6181 percent nocturnal awakening-free nights | Standard Deviation 38.4315 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Baseline (n=204,72,74,210) | 50.92 percent nocturnal awakening-free nights | Standard Deviation 37.72 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Percentage of Nocturnal Awakening-Free Nights at Week 51-52 | Change at Week 51-52 (n=111,36,39,111) | 23.3054 percent nocturnal awakening-free nights | Standard Deviation 36.2761 |
p-value: 0.5580% CI: [-4.483, 12.297]ANCOVA
p-value: 0.21580% CI: [-0.262, 15.579]ANCOVA
p-value: 0.41380% CI: [-2.006, 9.086]ANCOVA
Secondary
Change From Baseline in Rescue Medication Use at Week 51-52
Participants were provided inhalers of the same dose (medium- or high-dose) inhaled corticosteroid (ICS) plus long-acting beta antagonist (LABA) combination product as baseline prophylactic medication and continued with same dose throughout the study. Rescue medications such as short-term beta2 agonists were used as first-line treatment for worsening asthma symptoms. Investigator prescribed additional short term asthma controller medications included additional ICS, theophylline, inhaled cromones or antimuscarinics; if asthma symptoms remained mild but not resolved. If asthma symptoms worsened, participants received an oral corticosteroid burst. All rescue medications use with prophylactic medication (+ prophylactic) and without prophylactic medication (- prophylactic) was recorded in asthma symptom dairy by participant. Rescue medication use was analyzed on a bi-weekly basis and compared to baseline scores.
Time frame: Baseline up to Week 51-52
Population: The mITT population included all randomized participants who received any dose of investigational product. Here n signifies participants who were evaluable for this measure for the specified time point for each arm, respectively. Data was summarized together for EOS+ and EOS- Placebo arms and EOS+ and EOS- benralizumab 100 mg arms.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline without prophylactic (n=204,72,74,210) | 3.09 rescue medication per 2 weeks | Standard Deviation 2.55 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline with prophylactic (n=204,72,74,210) | 4.07 rescue medication per 2 weeks | Standard Deviation 3.34 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 -prophylactic(n=111,36,39,111) | -1.2540 rescue medication per 2 weeks | Standard Deviation 2.4571 |
| Eosinophilic Phenotype (EOS+) Placebo | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 +prophylactic(n=111,36,39,111) | -1.6855 rescue medication per 2 weeks | Standard Deviation 3.2875 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline with prophylactic (n=204,72,74,210) | 4.71 rescue medication per 2 weeks | Standard Deviation 5.56 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 -prophylactic(n=111,36,39,111) | -1.4116 rescue medication per 2 weeks | Standard Deviation 2.8722 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 +prophylactic(n=111,36,39,111) | -1.6810 rescue medication per 2 weeks | Standard Deviation 4.2247 |
| EOS+ Benralizumab, 2 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline without prophylactic (n=204,72,74,210) | 3.57 rescue medication per 2 weeks | Standard Deviation 3.67 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 -prophylactic(n=111,36,39,111) | -1.8804 rescue medication per 2 weeks | Standard Deviation 5.3129 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline with prophylactic (n=204,72,74,210) | 5.24 rescue medication per 2 weeks | Standard Deviation 6.4 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 +prophylactic(n=111,36,39,111) | -2.5118 rescue medication per 2 weeks | Standard Deviation 7.6814 |
| EOS+ Benralizumab, 20 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline without prophylactic (n=204,72,74,210) | 3.82 rescue medication per 2 weeks | Standard Deviation 4.34 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 +prophylactic(n=111,36,39,111) | -1.4693 rescue medication per 2 weeks | Standard Deviation 2.5603 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline with prophylactic (n=204,72,74,210) | 4.22 rescue medication per 2 weeks | Standard Deviation 3.9 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Baseline without prophylactic (n=204,72,74,210) | 3.16 rescue medication per 2 weeks | Standard Deviation 2.82 |
| EOS+ Benralizumab, 100 mg | Change From Baseline in Rescue Medication Use at Week 51-52 | Change Week 51-52 -prophylactic(n=111,36,39,111) | -1.1589 rescue medication per 2 weeks | Standard Deviation 2.0086 |
Comparison: Analysis reported for rescue medication use without prophylactic at Week 51-52.p-value: 0.64280% CI: [-0.654, 0.306]ANCOVA
Comparison: Analysis reported for rescue medication use without prophylactic at Week 51-52.p-value: 0.82480% CI: [-0.533, 0.756]ANCOVA
Comparison: Analysis reported for rescue medication use without prophylactic at Week 51-52.p-value: 0.9180% CI: [-0.297, 0.355]ANCOVA
Comparison: Analysis reported for rescue medication use with prophylactic at Week 51-52.p-value: 0.99280% CI: [-0.602, 0.593]ANCOVA
Comparison: Analysis reported for rescue medication use with prophylactic at Week 51-52.p-value: 0.62480% CI: [-0.548, 1.222]ANCOVA
Comparison: Analysis reported for rescue medication use with prophylactic at Week 51-52.p-value: 0.64580% CI: [-0.267, 0.567]ANCOVA
Secondary
Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD)
Time frame: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
Population: The PK Population included all participants who received at least one dose of benralizumab and had at least one quantifiable PK observation. One participant, randomized to the EOS- placebo group received a single dose of 100 mg benralizumab on Week 16 and was analyzed for PK in the 100 mg benralizumab group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD) | 17.3 microgram per milliliter | Standard Deviation 65.3 |
| EOS+ Benralizumab, 2 mg | Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD) | 9.10 microgram per milliliter | Standard Deviation 9.02 |
| EOS+ Benralizumab, 20 mg | Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD) | 8.69 microgram per milliliter | Standard Deviation 6.65 |
Secondary
Dose Response in EOS+ Participants
Time frame: Baseline up to Week 66
Population: Due to change in planned analysis after unblinding of study data, dose response was not performed.
Secondary
Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss)
Time frame: Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
Population: The Pharmacokinetic (PK) Population included all participants who received at least one dose of benralizumab and had at least one quantifiable PK observation. One participant, randomized to the EOS- placebo group received a single dose of 100 mg benralizumab on Week 16 and was analyzed for PK in the 100 mg benralizumab group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss) | 34.7 microgram per milliliter | Standard Deviation 131 |
| EOS+ Benralizumab, 2 mg | Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss) | 182 microgram per milliliter | Standard Deviation 180 |
| EOS+ Benralizumab, 20 mg | Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss) | 869 microgram per milliliter | Standard Deviation 665 |
Secondary
Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants
Immunogenicity assessment included determination of anti-drug (benralizumab) antibodies in serum samples. ADA positive was defined as a titer \>=50 at any point in the study. It was observed at baseline and any visit during the study.
Time frame: Baseline up to Week 92
Population: The mITT population included all randomized participants who received any dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Eosinophilic Phenotype (EOS+) Placebo | Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants | 3.8 percentage of participants |
| EOS+ Benralizumab, 2 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants | 42.0 percentage of participants |
| EOS+ Benralizumab, 20 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants | 30.9 percentage of participants |
| EOS+ Benralizumab, 100 mg | Percentage of Participants With Anti-Drug Antibodies (ADA) to Benralizumab in Eosinophilic Phenotype (EOS+) Participants | 25.6 percentage of participants |