Study to Evaluate the Efficacy and Safety of MEDI-563 in... | NCT01238861 | Trialant
NCT01238861
Sponsor
MedImmune LLC
Status
Completed
Last Update Posted
Nov 17, 2016Estimated
Enrollment
964Actual
Phase
Phase 2
Conditions
Asthma
Interventions
Benralizumab 2 mg
Benralizumab 20 mg
Benralizumab 100 mg
Placebo
Countries
United States
Argentina
Brazil
Bulgaria
Canada
Colombia
Mexico
Peru
Poland
Russia
Protocol Section
Identification Module
NCT ID
NCT01238861
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MI-CP220
Secondary IDs
ID
Type
Description
Link
2010-020126-17
EudraCT Number
Brief Title
Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma
Official Title
A Phase 2b, Dose-ranging Study to Evaluate the Efficacy and Safety of MEDI-563 in Adults With Uncontrolled Asthma
Acronym
Not provided
Organization
MedImmune LLCINDUSTRY
Status Module
Record Verification Date
Sep 2016
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 2010
Primary Completion Date
Mar 2013Actual
Completion Date
Aug 2013Actual
First Submitted Date
Nov 9, 2010
First Submission Date that Met QC Criteria
Nov 9, 2010
First Posted Date
Nov 11, 2010Estimated
Results Waived
Not provided
Results First Submitted Date
May 31, 2016
Results First Submitted that Met QC Criteria
Sep 28, 2016
Results First Posted Date
Nov 17, 2016Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Sep 28, 2016
Last Update Posted Date
Nov 17, 2016Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
MedImmune LLCINDUSTRY
Collaborators
Name
Class
MedImmune Ltd
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
No
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
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.
Conditions Module
Conditions
Asthma
Keywords
Asthma
Benralizumab
MEDI-563
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
964Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Eosinophilic phenotype (EOS+) Placebo
Placebo Comparator
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 injections subcutaneous injection every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Other: Placebo
EOS+ Benralizumab (2 mg)
Experimental
EOS+ participants received single benralizumab 2 milligram (mg) injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Biological: Benralizumab 2 mg
EOS+ Benralizumab (20 mg)
Experimental
EOS+ participants received single benralizumab 20 mg injection subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Biological: Benralizumab 20 mg
EOS+ Benralizumab (100 mg)
Experimental
EOS+ participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Biological: Benralizumab 100 mg
Non-eosinophil phenotype (EOS-) Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Benralizumab 2 mg
Biological
EOS+ participants received single benralizumab 2 milligram (mg) injection followed by a single placebo injection subcutaneously.
EOS+ Benralizumab (2 mg)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
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.
Week 1 up to Week 52
Secondary Outcomes
Measure
Description
Time Frame
Dose Response in EOS+ Participants
Baseline up to Week 66
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
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
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.
Castro M, Wenzel SE, Bleecker ER, Pizzichini E, Kuna P, Busse WW, Gossage DL, Ward CK, Wu Y, Wang B, Khatry DB, van der Merwe R, Kolbeck R, Molfino NA, Raible DG. Benralizumab, an anti-interleukin 5 receptor alpha monoclonal antibody, versus placebo for uncontrolled eosinophilic asthma: a phase 2b randomised dose-ranging study. Lancet Respir Med. 2014 Nov;2(11):879-890. doi: 10.1016/S2213-2600(14)70201-2. Epub 2014 Oct 8.
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.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
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.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
2
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
South Africa
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Placebo Comparator
EOS- (defined as ELEN Index negative and FeNO <50 ppb) participants received matching placebo subcutaneous every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Other: Placebo
EOS- Benralizumab (100 mg)
Experimental
EOS- participants received benralizumab 50 mg as two injections subcutaneously every 4 weeks for first 3 doses and then every 8 weeks for next 4 doses up to Week 40.
Biological: Benralizumab 100 mg
MEDI-563
Benralizumab 20 mg
Biological
EOS+ participants received single benralizumab 20 mg injection followed by a single placebo injection subcutaneously.
EOS+ Benralizumab (20 mg)
MEDI-563
Benralizumab 100 mg
Biological
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
EOS+ Benralizumab (100 mg)
EOS- Benralizumab (100 mg)
MEDI-563
Placebo
Other
EOS+ and EOS- participants received two placebo injections subcutaneously.
Eosinophilic phenotype (EOS+) Placebo
Non-eosinophil phenotype (EOS-) Placebo
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
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.
Baseline up to Week 92
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.
Baseline up to Week 52
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.
Baseline up to Week 52
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.
Baseline up to Week 51-52
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.
Baseline up to Week 51-52
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.
Baseline and Week 52
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.
Baseline and Week 52
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.
Baseline and Week 52
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.
Baseline and Week 52
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.
Baseline and Week 52
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.
Baseline and Week 52
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.
Baseline up to Week 51-52
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.
Baseline up to Week 52
Los Angeles
California
United States
Research Site
Orange
California
United States
Research Site
San Diego
California
United States
Research Site
Stockton
California
United States
Research Site
Colorado Springs
Colorado
United States
Research Site
Denver
Colorado
United States
Research Site
Waterbury
Connecticut
United States
Research Site
Kissimmee
Florida
United States
Research Site
Tampa
Florida
United States
Research Site
Stockbridge
Georgia
United States
Research Site
Normal
Illinois
United States
Research Site
Baltimore
Maryland
United States
Research Site
Rochester
Minnesota
United States
Research Site
St Louis
Missouri
United States
Research Site
Bellevue
Nebraska
United States
Research Site
Summit
New Jersey
United States
Research Site
Rochester
New York
United States
Research Site
Winston-Salem
North Carolina
United States
Research Site
Cincinnati
Ohio
United States
Research Site
Oklahoma City
Oklahoma
United States
Research Site
Blue Bell
Pennsylvania
United States
Research Site
Pittsburgh
Pennsylvania
United States
Research Site
Warwick
Rhode Island
United States
Research Site
Boerne
Texas
United States
Research Site
San Antonio
Texas
United States
Research Site
Seattle
Washington
United States
Research Site
Caba
Argentina
Research Site
Ciudad de Buenos Aires
Argentina
Research Site
San Miguel de Tucumán
Argentina
Research Site
Santa Fe
Argentina
Research Site
Curitiba
Brazil
Research Site
Florianópolis
Brazil
Research Site
Juiz de Fora
Brazil
Research Site
Porto Alegre
Brazil
Research Site
Rio de Janeiro
Brazil
Research Site
Salvador
Brazil
Research Site
Santo André
Brazil
Research Site
São Paulo
Brazil
Research Site
Pleven
Bulgaria
Research Site
Rousse
Bulgaria
Research Site
Sofia
Bulgaria
Research Site
Troyan Municipality
Bulgaria
Research Site
Brampton
Ontario
Canada
Research Site
Toronto
Ontario
Canada
Research Site
La Malbaie
Quebec
Canada
Research Site
Québec
Quebec
Canada
Research Site
Bogotá
Colombia
Research Site
Guadalajara
Mexico
Research Site
México
Mexico
Research Site
Monterrey
Mexico
Research Site
Morelia
Mexico
Research Site
Villahermosa
Mexico
Research Site
Zapopan
Mexico
Research Site
Lima
Peru
Research Site
San Borja
Peru
Research Site
San Isidro
Peru
Research Site
Surco
Peru
Research Site
Bialystok
Poland
Research Site
Bydgoszcz
Poland
Research Site
Lodz
Poland
Research Site
Lublin
Poland
Research Site
Ostrów Wielkopolski
Poland
Research Site
Piła
Poland
Research Site
Poznan
Poland
Research Site
Tarnów
Poland
Research Site
Warsaw
Poland
Research Site
Barnaul
Russia
Research Site
Chelyabinsk
Russia
Research Site
Kazan'
Russia
Research Site
Moscow
Russia
Research Site
Novosibirsk
Russia
Research Site
Saint Petersburg
Russia
Research Site
Yekaterinburg
Russia
Derived
Sridhar S, Liu H, Pham TH, Damera G, Newbold P. Modulation of blood inflammatory markers by benralizumab in patients with eosinophilic airway diseases. Respir Res. 2019 Jan 18;20(1):14. doi: 10.1186/s12931-018-0968-8.
FG001
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.
FG002
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.
FG003
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.
FG004
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.
FG005
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.
FG00080 subjects
FG00181 subjects
FG00281 subjects
FG00382 subjects
FG004142 subjects
FG005140 subjects
COMPLETED
FG00069 subjects
FG00173 subjects
FG00270 subjects
FG00369 subjects
FG004129 subjects
FG005125 subjects
NOT COMPLETED
FG00011 subjects
FG0018 subjects
FG00211 subjects
FG00313 subjects
FG00413 subjects
FG00515 subjects
Type
Comment
Reasons
Lost to Follow-up
FG0004 subjects
FG0012 subjects
FG0023 subjects
FG0031 subjects
FG0041 subjects
FG0052 subjects
Unplanned surgery
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Did not meet entry ACQ-6 criteria
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Incorrect enrollment/randomization
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Subject traveled to Argentina by 1 year
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Subject moved out of state/area
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG004
Strongyloides stercoralis antibodies +
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Personal problems
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Unable to continue visits
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Serious adverse event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Lack of compliance
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0006 subjects
FG0015 subjects
FG0024 subjects
FG0038 subjects
FG004
The modified intent-to-treat (mITT) population included all randomized participants who received any dose of investigational product.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
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.
BG001
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.
BG002
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.
BG003
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.
BG004
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.
BG005
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.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00080
BG00181
BG00281
BG00382
BG004142
BG005140
BG006606
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00045.6± 11.7
BG00147.1± 12.8
BG00246.6± 13.2
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00053
BG00158
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
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.
The modified intent-to-treat (mITT) population included all randomized participants who received any dose of investigational product.
Posted
Number
AER events/person-year
Week 1 up to Week 52
ID
Title
Description
OG000
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.
OG001
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.
OG002
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.
OG003
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.
Units
Counts
Participants
OG00080
OG00181
OG00281
OG003
Title
Denominators
Categories
Title
Measurements
OG0000.57
OG0010.65
OG0020.37
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Poisson Regression Method
0.781
Rate Ratio
1.09
2-Sided
80
0.74
1.59
The p-value was calculated by Poisson regression with over-dispersion adjustment factor. The correction for potential over dispersion was made by Pearson chi-square.
No
Superiority or Other
OG000
OG002
Secondary
Dose Response in EOS+ Participants
Due to change in planned analysis after unblinding of study data, dose response was not performed.
Posted
Baseline up to Week 66
ID
Title
Description
OG000
EOS+ Placebo
EOS+ participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
OG003
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.
Secondary
Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ss)
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.
Posted
Mean
Standard Deviation
microgram per milliliter
Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
ID
Title
Description
OG000
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.
OG001
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.
OG002
Benralizumab, 100 mg
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Secondary
Dose-Normalized Minimum Observed Serum Trough Concentration for Benralizumab at Steady-State (Ctrough, ssD)
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.
Posted
Mean
Standard Deviation
microgram per milliliter
Pre-dose (0 hour), Post-dose on Day 1, 6, Week 4, 16, 24, 32, 40, and 52
ID
Title
Description
OG000
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.
OG001
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.
OG002
Benralizumab, 100 mg
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
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.
The mITT population included all randomized participants who received any dose of investigational product.
Posted
Number
percentage of participants
Baseline up to Week 92
ID
Title
Description
OG000
EOS+ Placebo
EOS+ participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
OG003
EOS+ Benralizumab, 100 mg
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.
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.
Posted
Mean
Standard Deviation
units on a scale
Baseline up to Week 52
ID
Title
Description
OG000
EOS+ Placebo
EOS+ participants received two placebo injections subcutaneously.
OG001
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.
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.
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.
Posted
Mean
Standard Deviation
units on a scale
Baseline up to Week 52
ID
Title
Description
OG000
Placebo
EOS+ and EOS- participants received two placebo injections subcutaneously.
OG001
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.
OG002
EOS+ Benralizumab, 20 mg
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.
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.
Posted
Mean
Standard Deviation
units on a scale
Baseline up to Week 51-52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
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.
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.
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.
Posted
Mean
Standard Deviation
rescue medication per 2 weeks
Baseline up to Week 51-52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
EOS+ Benralizumab, 2 mg
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.
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.
Posted
Mean
Standard Deviation
liters
Baseline and Week 52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
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.
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.
Posted
Mean
Standard Deviation
liters
Baseline and Week 52
ID
Title
Description
OG000
EOS+ Placebo
EOS+ participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
OG003
EOS+ Benralizumab, 100 mg
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.
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.
Posted
Mean
Standard Deviation
liters per minute
Baseline and Week 52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
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.
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.
Posted
Mean
Standard Deviation
units on a scale
Baseline and Week 52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
EOS+ Benralizumab, 2 mg
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.
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.
Posted
Mean
Standard Deviation
units on a scale
Baseline and Week 52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
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.
Posted
Mean
Standard Deviation
units on a scale
Baseline and Week 52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
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.
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.
Posted
Mean
Standard Deviation
percent nocturnal awakening-free nights
Baseline up to Week 51-52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
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.
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.
Posted
Mean
Standard Deviation
parts per billion
Baseline up to Week 52
ID
Title
Description
OG000
Placebo
Participants received two placebo injections subcutaneously.
OG001
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.
OG002
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.
OG003
Benralizumab (100 mg)
Time Frame
From initiation of investigational product administration up to Week 92
Description
The safety population included all participants who received any investigational product and had safety data available for analysis. One participant, randomized to the EOS- placebo group received a single dose of 100 mg benralizumab on Week 16 and was analyzed for safety in the 100 mg benralizumab group .
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
EOS POS Placebo
EOS+ participants received two placebo injections subcutaneously.
7
80
44
80
EG001
EOS POS Benralizumab 2 mg
EOS+ participants received single benralizumab 2 milligram (mg) injection followed by a single placebo injection subcutaneously.
10
81
54
81
EG002
EOS POS Benralizumab 20 mg
EOS+ participants received single benralizumab 20 mg injection followed by a single placebo injection subcutaneously.
6
81
57
81
EG003
EOS POS Benralizumab 100 mg
EOS+ participants received two benralizumab 50 mg injections subcutaneously.
6
82
68
82
EG004
EOS NEG Placebo
EOS- participants received two placebo injections subcutaneously.
16
141
94
141
EG005
EOS NEG Benralizumab 100 mg
EOS- participants received two benralizumab 50 mg injections subcutaneously.
18
141
93
141
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Acute myocardial infarct
Cardiac disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0021 events1 affected81 at risk
EG0030 events0 affected82 at risk
EG0040 events0 affected141 at risk
EG0050 events0 affected141 at risk
Atrial fibrillation
Cardiac disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Cardiac failure acute
Cardiac disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0022 events2 affected81 at risk
EG003
Supraventricular tachyca
Cardiac disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Abdominal hernia
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Gastrooesophageal reflux
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Cholecystitis acute
Hepatobiliary disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Cholecystitis infective
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Eczema infected
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Enteritis infectious
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Gastritis viral
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0011 events1 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Abdominal wound dehiscen
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0021 events1 affected81 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0012 events2 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0011 events1 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Osteochondrosis
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0011 events1 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Spinal osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Fibrous histiocytoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Malignant melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Thyroid neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0021 events1 affected81 at risk
EG003
Convulsion
Nervous system disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0011 events1 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Grand mal convulsion
Nervous system disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0011 events1 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Syncope
Nervous system disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Depression
Psychiatric disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA 16.0
Systematic Assessment
EG0002 events2 affected80 at risk
EG0012 events2 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Asthmatic crisis
Respiratory, thoracic and mediastinal disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0010 events0 affected81 at risk
EG0021 events1 affected81 at risk
EG003
Nasal polyps
Respiratory, thoracic and mediastinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Erythema nodosum
Skin and subcutaneous tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0021 events1 affected81 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Umbilical hernia
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Anaphylactic reaction
Immune system disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Lower respiratory tract
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Post procedural cellulit
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0011 events1 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Postoperative wound infe
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Tonsillitis bacterial
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Ulna fracture
Injury, poisoning and procedural complications
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0011 events1 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Uterine leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0021 events1 affected81 at risk
EG003
Interstitial lung diseas
Respiratory, thoracic and mediastinal disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Hypertension
Vascular disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Polyarteritis nodosa
Vascular disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0010 events0 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Injection site erythema
General disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0012 events2 affected81 at risk
EG0024 events2 affected81 at risk
EG00317 events8 affected82 at risk
EG0040 events0 affected141 at risk
EG00517 events10 affected141 at risk
Influenza
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0004 events4 affected80 at risk
EG0015 events3 affected81 at risk
EG0027 events7 affected81 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0006 events3 affected80 at risk
EG0017 events4 affected81 at risk
EG0023 events3 affected81 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 16.0
Systematic Assessment
EG0003 events2 affected80 at risk
EG0013 events3 affected81 at risk
EG0022 events2 affected81 at risk
EG003
Injection site pain
General disorders
MedDRA 16.0
Systematic Assessment
EG0000 events0 affected80 at risk
EG0016 events6 affected81 at risk
EG00217 events4 affected81 at risk
EG003
Pyrexia
General disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0014 events4 affected81 at risk
EG0023 events3 affected81 at risk
EG003
Acute sinusitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0007 events3 affected80 at risk
EG0016 events4 affected81 at risk
EG0022 events2 affected81 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0004 events3 affected80 at risk
EG00110 events8 affected81 at risk
EG0028 events6 affected81 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG00013 events8 affected80 at risk
EG00119 events11 affected81 at risk
EG00213 events7 affected81 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0003 events3 affected80 at risk
EG00110 events8 affected81 at risk
EG0023 events3 affected81 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0003 events3 affected80 at risk
EG0013 events3 affected81 at risk
EG0023 events3 affected81 at risk
EG003
Upper respiratory tract
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0006 events4 affected80 at risk
EG00112 events7 affected81 at risk
EG0028 events7 affected81 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 16.0
Systematic Assessment
EG0004 events4 affected80 at risk
EG0013 events2 affected81 at risk
EG0021 events1 affected81 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0015 events4 affected81 at risk
EG0026 events5 affected81 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0003 events3 affected80 at risk
EG0014 events4 affected81 at risk
EG0022 events2 affected81 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 16.0
Systematic Assessment
EG0001 events1 affected80 at risk
EG0012 events2 affected81 at risk
EG0023 events3 affected81 at risk
EG003
Headache
Nervous system disorders
MedDRA 16.0
Systematic Assessment
EG00013 events8 affected80 at risk
EG00113 events8 affected81 at risk
EG00210 events6 affected81 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA 16.0
Systematic Assessment
EG00051 events30 affected80 at risk
EG00159 events28 affected81 at risk
EG00242 events24 affected81 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 16.0
Systematic Assessment
EG0003 events3 affected80 at risk
EG0015 events3 affected81 at risk
EG00213 events8 affected81 at risk
EG003
Hypertension
Vascular disorders
MedDRA 16.0
Systematic Assessment
EG0002 events1 affected80 at risk
EG0013 events3 affected81 at risk
EG0020 events0 affected81 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.
Point of Contact
Title
Organization
Phone
Extension
Email
Rene van der Merwe, MBChB, MFPM, Medical Officer
MedImmune, LLC
301-398-0000
vandermerwer@medimmune.com
ID
Term
D001249
Asthma
Ancestor Terms
ID
Term
D001982
Bronchial Diseases
D012140
Respiratory Tract Diseases
D008173
Lung Diseases, Obstructive
D008171
Lung Diseases
D012130
Respiratory Hypersensitivity
D006969
Hypersensitivity, Immediate
D006967
Hypersensitivity
D007154
Immune System Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C571386
benralizumab
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
1 subjects
FG0051 subjects
1 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0051 subjects
0 subjects
FG0051 subjects
0 subjects
FG0051 subjects
0 subjects
FG0050 subjects
10 subjects
FG0059 subjects
47.8
± 12.9
BG00450.0± 12.3
BG00550.0± 11.5
BG00648.3± 12.4
48
BG00360
BG004100
BG00598
BG006417
Male
BG00027
BG00123
BG00233
BG00322
BG00442
BG00542
BG006189
82
0.34
Poisson Regression Method
0.173
Rate Ratio
0.64
2-Sided
80
0.42
0.97
The p-value was calculated by Poisson regression with over-dispersion adjustment factor. The correction for potential over dispersion was made by Pearson chi-square.
No
Superiority or Other
OG000
OG003
Poisson Regression Method
0.096
Rate ratio
0.59
2-Sided
80
0.40
0.89
The p-value was calculated by Poisson regression with over-dispersion adjustment factor. The correction for potential over dispersion was made by Pearson chi-square.
No
Superiority or Other
Units
Counts
Participants
OG0000
OG0010
OG0020
OG0030
Units
Counts
Participants
OG00081
OG00181
OG002223
Title
Denominators
Categories
Title
Measurements
OG00034.7± 131
OG001182± 180
OG002869± 665
Units
Counts
Participants
OG00081
OG00181
OG002223
Title
Denominators
Categories
Title
Measurements
OG00017.3± 65.3
OG0019.10± 9.02
OG0028.69± 6.65
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.
Units
Counts
Participants
OG00080
OG00181
OG00281
OG00382
Title
Denominators
Categories
Title
Measurements
OG0003.8
OG00142.0
OG00230.9
OG00325.6
OG002
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.
OG003
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.
OG004
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.
OG005
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.
Units
Counts
Participants
OG00080
OG00181
OG00281
OG00382
OG004142
OG005140
Title
Denominators
Categories
Baseline (n=80,80,80,82,142,140)
Title
Measurements
OG0002.7479± 0.9762
OG0012.6479± 0.9908
OG0022.4750± 0.9106
OG0032.5346± 0.9728
OG0042.4742± 0.8408
OG0052.6381± 0.8330
Change at Week 52 (n=34,42,40,39,64,73)
Title
Measurements
OG000-0.8922± 1.1969
OG001-1.1032± 1.1207
OG002-1.2500± 1.2247
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by analysis of covariance (ANCOVA) with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.125
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.074
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.057
No
Superiority or Other
OG004
OG005
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.010
No
Superiority or Other
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.
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=71,27,25,81)
Title
Measurements
OG0004.3± 2.0
OG0014.8± 2.0
OG0025.3± 1.8
OG0034.4± 2.1
Change at Week 52 (n=89,39,39,106)
Title
Measurements
OG000-0.4± 2.90
OG001-0.8± 2.01
OG002-1.0± 2.96
OG003
OG002
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.
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=204,72,74,210)
Title
Measurements
OG0001.58± 0.60
OG0011.65± 0.65
OG0021.60± 0.61
OG0031.60± 0.62
Change at Week 51-52 (n=111,36,39,111)
Title
Measurements
OG000-0.37± 0.61
OG001-0.56± 0.76
OG002-0.56± 0.69
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.131
Mean Difference (Final Values)
-0.182
2-Sided
80
-0.336
-0.028
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.126
Mean Difference (Final Values)
-0.173
2-Sided
80
-0.317
-0.028
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.097
Mean Difference (Final Values)
-0.140
2-Sided
80
-0.247
-0.032
No
Superiority or Other
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.
OG002
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.
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline without prophylactic (n=204,72,74,210)
Title
Measurements
OG0003.09± 2.55
OG0013.57± 3.67
OG0023.82± 4.34
OG0033.16± 2.82
Baseline with prophylactic (n=204,72,74,210)
Title
Measurements
OG0004.07± 3.34
OG0014.71± 5.56
OG0025.24± 6.40
OG003
Change Week 51-52 -prophylactic(n=111,36,39,111)
Title
Measurements
OG000-1.2540± 2.4571
OG001-1.4116± 2.8722
OG002-1.8804± 5.3129
OG003
Change Week 51-52 +prophylactic(n=111,36,39,111)
Title
Measurements
OG000-1.6855± 3.2875
OG001-1.6810± 4.2247
OG002-2.5118± 7.6814
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Analysis reported for rescue medication use without prophylactic at Week 51-52.
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.642
Mean Difference (Final Values)
-0.174
2-Sided
80
-0.654
0.306
No
Superiority or Other
OG000
OG002
Analysis reported for rescue medication use without prophylactic at Week 51-52.
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.824
Mean Difference (Final Values)
0.111
2-Sided
80
-0.533
0.756
No
Superiority or Other
OG000
OG003
Analysis reported for rescue medication use without prophylactic at Week 51-52.
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.910
Mean Difference (Final Values)
0.029
2-Sided
80
-0.297
0.355
No
Superiority or Other
OG000
OG001
Analysis reported for rescue medication use with prophylactic at Week 51-52.
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.992
Mean Difference (Final Values)
-0.004
2-Sided
80
-0.602
0.593
No
Superiority or Other
OG000
OG002
Analysis reported for rescue medication use with prophylactic at Week 51-52.
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.624
Mean Difference (Final Values)
0.337
2-Sided
80
-0.548
1.222
No
Superiority or Other
OG000
OG003
Analysis reported for rescue medication use with prophylactic at Week 51-52.
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.645
Mean Difference (Final Values)
0.150
2-Sided
80
-0.267
0.567
No
Superiority or Other
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=215,80,81,218)
Title
Measurements
OG0002.033± 0.669
OG0011.978± 0.701
OG0022.080± 0.751
OG0032.012± 0.672
Change at Week 52 (n=150,51,58,160)
Title
Measurements
OG0000.0098± 0.3615
OG0010.1631± 0.4691
OG0020.1847± 0.5234
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.014
Mean Difference (Final Values)
0.157
2-Sided
80
0.076
0.237
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.004
Mean Difference (Final Values)
0.184
2-Sided
80
0.102
0.266
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.026
Mean Difference (Final Values)
0.091
2-Sided
80
0.039
0.143
No
Superiority or Other
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.
OG004
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.
OG005
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.
Units
Counts
Participants
OG00080
OG00181
OG00281
OG00382
OG004142
OG005140
Title
Denominators
Categories
Baseline (n=80,80,81,82,135,136)
Title
Measurements
OG0003.282± 1.030
OG0013.069± 0.957
OG0023.285± 1.028
OG0033.110± 0.851
OG0043.043± 0.864
OG0053.126± 0.981
Change at Week 52 (n=51,51,58,59,99,101)
Title
Measurements
OG0000.029± 0.514
OG0010.129± 0.565
OG0020.190± 0.586
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.384
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.092
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.134
No
Superiority or Other
OG004
OG005
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.129
No
Superiority or Other
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=215,80,81,218)
Title
Measurements
OG000319.3± 104.7
OG001325.5± 101.6
OG002323.1± 100.8
OG003323.8± 101.7
Change at Week 52 (n=150,51,58,160)
Title
Measurements
OG00013.0± 64.6
OG00129.0± 64.1
OG00245.9± 95.5
OG003
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.
OG002
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.
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=214,78,80,217)
Title
Measurements
OG0003.72± 1.04
OG0013.72± 1.17
OG0023.79± 1.06
OG0033.72± 1.01
Change at Week 52 (n=88,39,38,105)
Title
Measurements
OG0000.9634± 1.3342
OG0011.2612± 1.2082
OG0021.4474± 1.4262
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.069
Mean Difference (Final Values)
0.404
2-Sided
80
0.121
0.687
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.049
Mean Difference (Final Values)
0.462
2-Sided
80
0.163
0.761
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.168
Mean Difference (Final Values)
0.238
2-Sided
80
0.017
0.459
No
Superiority or Other
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.
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=213,79,74,209)
Title
Measurements
OG0000.7629± 0.2153
OG0010.7418± 0.2376
OG0020.7877± 0.1878
OG0030.7679± 0.1623
Change at Week 52 (n=148,58,53,161)
Title
Measurements
OG0000.0853± 0.2096
OG0010.0822± 0.3137
OG0020.1223± 0.2132
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.510
Mean Difference (Final Values)
-0.020
2-Sided
80
-0.058
0.019
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.113
Mean Difference (Final Values)
0.041
2-Sided
80
0.008
0.074
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.599
Mean Difference (Final Values)
0.011
2-Sided
80
-0.016
0.038
No
Superiority or Other
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=213,79,74,208)
Title
Measurements
OG00065.0798± 17.8903
OG00165.4937± 18.5063
OG00264.3378± 18.1427
OG00364.6250± 19.7778
Change at Week 52 (n=148,58,53,161)
Title
Measurements
OG00012.8041± 19.1036
OG00112.5517± 20.8008
OG00215.4906± 21.7297
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.871
Mean Difference (Final Values)
-0.373
2-Sided
80
-3.333
2.586
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.227
Mean Difference (Final Values)
2.857
2-Sided
80
-0.175
5.889
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.503
Mean Difference (Final Values)
1.139
2-Sided
80
-1.041
3.319
No
Superiority or Other
OG003
Benralizumab (100 mg)
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=204,72,74,210)
Title
Measurements
OG00052.05± 36.96
OG00145.07± 40.04
OG00251.57± 39.72
OG00350.92± 37.72
Change at Week 51-52 (n=111,36,39,111)
Title
Measurements
OG00019.7595± 39.1388
OG00127.1749± 41.7342
OG00229.6181± 38.4315
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.550
Mean Difference (Final Values)
3.907
2-Sided
80
-4.483
12.297
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.215
Mean Difference (Final Values)
7.659
2-Sided
80
-0.262
15.579
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.413
Mean Difference (Final Values)
3.540
2-Sided
80
-2.006
9.086
No
Superiority or Other
EOS+ and EOS- participants received two benralizumab 50 mg injections subcutaneously.
Units
Counts
Participants
OG000222
OG00181
OG00281
OG003222
Title
Denominators
Categories
Baseline (n=222,81,81,222)
Title
Measurements
OG00026.88± 23.57
OG00139.52± 32.67
OG00240.79± 31.03
OG00326.68± 23.10
Change at Week 52 (n=148,57,56,157)
Title
Measurements
OG0001.2523± 16.0200
OG001-3.2222± 33.2543
OG002-6.1905± 30.1103
OG003
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.896
No
Superiority or Other
OG000
OG002
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.
0.944
No
Superiority or Other
OG000
OG003
ANCOVA
P-value was calculated by ANCOVA with treatment, baseline inhaled steroid status and baseline observed value as covariates.