Efficacy and Safety Study of Benralizumab to Reduce OCS U... | NCT02075255

Label	Type	Description	Intervention Names
Benralizumab Arm A	Experimental	Benralizumab administered subcutaneously every 4 weeks	Biological: Benralizumab
Benralizumab Arm B	Experimental	Benralizumab administered subcutaneously every 4 weeks for the first 3 dose and then every 8 weeks; matching placebo subcutaneously at the 4 week interim to maintain the blind.	Biological: Benralizumab
Placebo	Placebo Comparator	Placebo administered subcutaneously every 4 weeks	Biological: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Benralizumab	Biological	Benralizumab administered subcutaneously every 4 weeks	Benralizumab Arm A

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control	Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.	Week 28

Secondary Outcomes

Measure	Description	Time Frame
Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control	Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose.	Week 28
Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control for Patients With Baseline Eosinophils >=300/uL

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provision of informed consent prior to any study specific procedures.
Female and male aged from 18 to 75 years, inclusively.
History of physician-diagnosed asthma requiring treatment with medium dose ICS and LABA.
Elevated level of peripheral blood eosinophil
Documented treatment with high-dose ICS and LABA for at least 6 months prior to Visit 1
Chronic oral corticosteroid therapy for at least 6 continuous months directly preceding Visit 1. Subjects must be on doses equivalent to 7.5 - 40 mg/day of prednisolone/prednisone at Visit 1 and be on a stable dose for at least 2 weeks prior to randomization. Patients must agree to switch to study required prednisone/prednisolone as their oral corticosteroid for the duration of the study.
Patients with documented failures of OCS reduction within 6 months prior to Visit 1 will not be required to proceed through the dose optimization phase during run-in.
Morning pre-bronchodilator (Pre-BD) FEV1 of <80% predicted
Evidence of asthma as documented by either:

Airway reversibility (FEV1 ≥12% and 200 mL) demonstrated at Visit 1, Visit 2, or Visit 3 using the Maximum Post-bronchodilator Procedure OR Documented reversibility in the previous 24 months prior to Visit 1 OR Airway hyperresponsiveness (PC20 FEV1 methacholine concentration ≤8mg/mL) documented in the previous 12 months prior to planned date of randomization OR Airflow variability in clinic FEV1 ≥20% between 2 consecutive clinic visits documented in the 12 months prior to the planned date of randomization (FEV1 recorded during an exacerbation should not be considered for this criterion).

All patients must have reversibility testing performed before randomization to establish a baseline characteristic.

If patients do not demonstrate airway reversibility at either Visit 1 or Visit 2 and this is needed to qualify the patient for randomization, the site should reiterate the need to withhold short- and long-acting bronchodilators prior to Visit 3 in an effort to meet this inclusion criterion.
At least 1 documented asthma exacerbation in the previous 12 months prior to the date informed consent is obtained
Optimized OCS dose reached at least 2 weeks prior to randomization
Additional asthma controller medication must not have been initiated during run in/optimization period (not applicable for management of exacerbations during screening/ run in optimization phase)
At least 70% compliance with OCS use
At least 70% compliance with usual asthma controller ICS-LABA
Minimum 70% (i.e. 10 of 14 days) compliance with asthma daily diary (morning and evening diary)

Exclusion criteria:

Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
- Affect the safety of the patient throughout the study
- Influence the findings of the studies or their interpretations
- Impede the patient's ability to complete the entire duration of study
Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during run-in/optimization period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study
History of life-threatening asthma
Asthma control reached at an OCS dose of ≤5mg during run-in/OCS optimization phase
Qualifies for 3 consecutive dose reductions at Visits 2-4 and continues to meet OCS dose reduction criteria at Visit 5
Receipt of oral corticosteroids, other than prednisone or prednisolone, as the maintenance oral steroid controller for asthma symptoms from Visit 1 and throughout the study.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period

Name	Affiliation	Role
Parameswaran Nair, MD,PhD,FRCP,FRCPC	St Joseph's Healthcare Hamilton Firestone Institute for Respiratory Health 50 Charlton Avenue East Hamilton	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Los Angeles	California	90025	United States
Research Site

PubMed Identifier	Type	Citation	Retractions
28530840	Background	Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.
35287231	Derived

Label	URL
CSP redacted	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
FG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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

Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control

Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. The percentage reduction from baseline is defined as: {(Baseline dose-final dose)/baseline dose}*100%. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.

Full analysis set

Posted

Median

95% Confidence Interval

Percent

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG00072 OG00173 OG00275

Title

Denominators

Categories

Title	Measurements
	OG00075.00(50.00 to 83.30) OG00175.00(60.00 to 87.50) OG00225.00(0.00 to 33.30)

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 OG002		Wilcoxon (Mann-Whitney)		<0.001		Median Difference (Final Values)	33.3			2-Sided	95	16.70	50.00			Hodges-Lehmann estimate is used.		Superiority or Other
OG001 OG002		Wilcoxon (Mann-Whitney)

Secondary

Number and Percentage of Patients in Different Categories of Percent Reduction From Baseline in Final OCS Dose While Maintaining Asthma Control

Number and percentage of patients in different categories of percent reduction from baseline in final OCS dose.

Full analysis set

Posted

Count of Participants

Participants

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Percentage Reduction in Final OCS Dose Compared With Baseline While Maintaining Asthma Control for Patients With Baseline Eosinophils >=300/uL

Full analysis set, baseline blood eosinophil >=300/uL

Posted

Median

95% Confidence Interval

Percent

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

The Percentage of Patients With ≥50% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control

Full analysis set

Posted

Count of Participants

Participants

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

The Proportion of Eligible Patients With ≥100% Reduction in Average Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control

Full analysis set, eligible for 100% reduction (ie, patients with baseline OCS dose <= 12.5 mg)

Posted

Number

Participants

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

The Proportion of Patients With ≤5.0 mg Reduction on Daily OCS Dose at Visit 14 Compared With Baseline Dose at Visit 6, While Maintaining Asthma Control.

Baseline OCS dose is the dose upon which the patient is stabilised at randomisation (Week 0). Final OCS dose is the dose at Week 28. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.

Full analysis set

Posted

Number

Participants

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units

Secondary

The Proportion of Patients With Average Final OCS Dose ≤5.0 mg Daily at Visit 14, While Maintaining Asthma Control

Final OCS dose is the dose at Week 28. If a patient discontinues from the study during a given dose reduction period, or the patient experiences an exacerbation between Weeks 24 and 28 or immediately before discontinuation, then the final OCS dose will be 1 dose level higher than that which directly preceded the event.

Full analysis set

Posted

Number

Participants

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

Number and Percentage of Patients With ≥1 Asthma Exacerbation

Number and percentage of patients with at least one post randomisation asthma exacerbation.

Full analysis set

Posted

Count of Participants

Participants

Immediately following the randomisation through Study Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Time to the First Asthma Exacerbation

Time to the first occurrence of asthma exacerbation post randomisation

Full analysis set

Posted

Median

95% Confidence Interval

Days

The time from randomisation to the date of first asthma exacerbation over 28 weeks

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Time to the First Asthma Exacerbation Requiring Hospitalization or ER Visit

Time to the first exacerbation requiring hospitalization or ER visit post randomisation

Full analysis set

Posted

Median

95% Confidence Interval

Days

The time from randomisation to the date of first asthma exacerbation associated with hospitalization or ER over 28 weeks.

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

The Annualized Rate of Asthma Exacerbation

The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator adjusted by the time of follow-up.

Full analysis set

Posted

Least Squares Mean

95% Confidence Interval

events/year

The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

The Annualized Rate of Asthma Exacerbations That Are Associated With an Emergency Room Visit or a Hospitalization

The annualized exacerbation rate is based on unadjudicated exacerbation reported by the investigator that are associated with an emergency room visit or a hospitalization adjusted by the time of follow-up.

Full analysis set

Posted

Least Squares Mean

95% Confidence Interval

events/year

The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

Number of Days in Hospital Due to Asthma

Number of days in hospital due to asthma, if none, 0 day is considered

Full analysis set

Posted

Mean

Standard Deviation

Days

The time from randomisation to the date of week 28 visit (end of treatment) or last contact if the patient is lost to follow up

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 28 in Pre-bronchodilator FEV1

Baseline is defined as the last non-missing value prior to the first dose of study treatment. Change from baseline to Week 28 in two treatment groups is compared to placebo group.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Liter

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

Change From Baseline to Week 28 in Asthma Symptom Scores (Total)

Asthma symptoms during night time and daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma), and total asthma symptom score is the sum of the daytime and night time score (0 to 6). Lower score (0) is indicating better asthma symptom, while higher score (6) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Scores on a scale

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo

Secondary

Change From Baseline to Week 28 in Asthma Symptom Scores (Daytime)

Asthma symptoms during daytime are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma). Lower score (0) is indicating better asthma symptom, while higher score (3) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Scores on a scale

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

Change From Baseline to Week 28 in Asthma Symptom Scores (Nighttime)

Asthma symptoms during night time are recorded by the patient in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma, or unable to do normal activities due to asthma). Lower score (0) is indicating better asthma symptom, while higher score (3) is indicating worse asthma symptom. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each time point is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Scores on a scale

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

Change From Baseline to Week 28 in Rescue Medication Use

Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this will be considered as missing. The number of inhalations (puffs) per day will be calculated as follows: Number of night inhaler puffs + 2 x [number of night nebulizer times] + number of day inhaler puffs + 2 x [number of day nebulizer times].

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

number of puffs per day

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

Change From Baseline to Week 28 in Home Lung Function (Morning Peak Expiratory Flow)

Morning peak expiratory flow change from baseline to week 28. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Liter/min

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

Change From Baseline to Week 28 in Home Lung Function (Evening Peak Expiratory Flow)

Evening peak expiratory flow change from baseline to week 28. Baseline is defined as the average of data collected from the evening of study day -14 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Liter/min

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

Change From Baseline to Week 28 in the Proportion of Nights With Awakening Due to Asthma Requiring Rescue Medication

Baseline is defined as the proportion of nights from the evening of study day -14 to the morning of study day 1.Each timepoint is calculated as bi-weekly proportions based on daily diary data. If more than 50% of data are missing in a 14 day period then this will be considered as missing.Proportion of nights with noctural awakenings is defined as the number of nights with awakenings due to asthma and requiring rescue medication divided by number of nights with data.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Proportion

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

Change From Baseline to Week 28 in ACQ-6

ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Scores on a scale

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts

Secondary

ACQ-6 Responders (Improvement) at Week 28

Improvement is defined as ACQ-6 (End of treatment - baseline) <= -0.5. No change is defined as ACQ-6 (End of treatment - baseline) >-0.5 and <0.5. Deterioration is defined as ACQ-6 (End of treatment - baseline) >= 0.5. ACQ-6 score is defined as the average of the first 6 items of the ACQ questionnaire on symptoms, activity limitations and rescue medication.Scores range from 0 (totally controlled) to 6 (severely uncontrolled). Baseline is defined as the last non-missing value prior to randomisation. End of treatment is defined as week 28. Patients with missing or non-evaluable ACQ-6 at week 28 are considered non-responder.

Full analysis set

Posted

Number

Participants

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

Change From Baseline at Week 28 in AQLQ(S)+12 (Overall)

AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of >=0.5 are considered clinically meaningful.

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

Scores on a scale

Change from baseline at week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants

Secondary

AQLQ(s)+12 Responders (Improvement) at Week 28

AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. Improvement is defined as AQLQ(S)+12 (End of treatment - baseline)>=0.5. No change is defined as AQLQ(S)+12 (End of treatment - baseline) >-0.5 and <0.5. Deterioration is defined as AQLQ(S)+12 (End of treatment - baseline) <= -0.5. Baseline is defined as the last AQLQ(S)+12 score prior to randomisation. End of treatment is defined as week 28. Patients with missing or non-evaluable score at week 28 are considered as non-responder.

Full analysis set

Posted

Number

Participants

Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Secondary

Extent of Exposure

Duration of exposure from first dose date to last dose date.

Safety analysis set

Posted

Mean

Standard Deviation

Days

From first dose to Week 24

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Serum Concentration of Benralizumab

Pre-dose serum concentrations at each visit

PK analysis set

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-first dose to Week 36

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Anti-drug Antibody Response

Number and percentage of patients in different ADA response categories

Safety analysis set

Posted

Count of Participants

Participants

From baseline to follow-up Week 36

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Percent Change From Baseline in Blood Eosinophil Counts

Percent change from baseline in blood eosinophil counts at week 28

Full analysis set. Number of participants analyzed contains number of participants who had value at Week 28.

Posted

Mean

Standard Deviation

percent change

Change from baseline at Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Total Lung Capacity

Change from baseline in total lung capacity

Global Sputum Substudy

Posted

Mean

Standard Deviation

Liter

From baseline to Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Residual Volume

Change from baseline in residual volume

Global Sputum Substudy

Posted

Mean

Standard Deviation

Liter

From baseline to Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Vital Capacity

Change from baseline in vital capacity

Global Sputum Substudy

Posted

Mean

Standard Deviation

Liter

From baseline to Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Functional Residual Capacity

Change from baseline in functional residual capacity

Global Sputum Substudy

Posted

Mean

Standard Deviation

Liter

From baseline to Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Secondary

Inspiratory Capacity

Change from baseline in inspiratory capacity

Global Sputum Substudy

Posted

Mean

Standard Deviation

Liter

From baseline to Week 28

ID	Title	Description
OG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
OG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
OG002	Placebo	Placebo administered subcutaneously

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0011 events1 affected73 at risk EG0020 events0 affected75 at risk
Atrial flutter	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0021 events1 affected75 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0011 events1 affected73 at risk EG0020 events0 affected75 at risk
Pericarditis	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0021 events1 affected75 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0011 events1 affected73 at risk EG0020 events0 affected75 at risk
Umbilical hernia	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk
Adverse drug reaction	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk
Gallbladder polyp	Hepatobiliary disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0011 events1 affected73 at risk EG0020 events0 affected75 at risk
Hypersensitivity	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk
Atypical pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0021 events1 affected75 at risk
Chronic sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0021 events1 affected75 at risk
Colonic abscess	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0021 events1 affected75 at risk
Influenza	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0022 events2 affected75 at risk
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0012 events2 affected73 at risk EG0023 events3 affected75 at risk
Pneumonia staphylococcal	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0021 events1 affected75 at risk
Urinary tract infection bacterial	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk
Urosepsis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk
Presyncope	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0011 events1 affected73 at risk EG0020 events0 affected75 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected72 at risk EG0011 events1 affected73 at risk EG0025 events4 affected75 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0021 events1 affected75 at risk
Status asthmaticus	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0023 events3 affected75 at risk
Dermatitis atopic	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0020 events0 affected75 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vertigo	Ear and labyrinth disorders	MedDRA 18.1	Systematic Assessment	EG0005 events1 affected72 at risk EG0013 events3 affected73 at risk EG0022 events2 affected75 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected72 at risk EG0010 events0 affected73 at risk EG0023 events3 affected75 at risk
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0007 events5 affected72 at risk EG00110 events8 affected73 at risk EG00213 events12 affected75 at risk
Influenza	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected72 at risk EG0011 events1 affected73 at risk EG0025 events5 affected75 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00013 events11 affected72 at risk EG00114 events12 affected73 at risk EG00217 events15 affected75 at risk
Oral candidiasis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected72 at risk EG0010 events0 affected73 at risk EG0024 events4 affected75 at risk
Rhinitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected72 at risk EG0017 events6 affected73 at risk EG0022 events2 affected75 at risk
Sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0008 events5 affected72 at risk EG0015 events4 affected73 at risk EG00211 events8 affected75 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0007 events4 affected72 at risk EG0016 events5 affected73 at risk EG0027 events5 affected75 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected72 at risk EG0012 events2 affected73 at risk EG0025 events4 affected75 at risk
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0007 events5 affected72 at risk EG00110 events6 affected73 at risk EG0024 events4 affected75 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG00011 events6 affected72 at risk EG0012 events1 affected73 at risk EG00217 events14 affected75 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected72 at risk EG0011 events1 affected73 at risk EG0024 events4 affected75 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected72 at risk EG0011 events1 affected73 at risk EG0024 events4 affected75 at risk
Hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected72 at risk EG0013 events3 affected73 at risk EG0022 events2 affected75 at risk

ID	Term
D001249	Asthma
D001982	Bronchial Diseases
D012140	Respiratory Tract Diseases
D008171	Lung Diseases
D008173	Lung Diseases, Obstructive

ID	Term
D012130	Respiratory Hypersensitivity
D006969	Hypersensitivity, Immediate
D006967	Hypersensitivity
D007154	Immune System Diseases

ID	Title	Description
BG000	Benralizumab 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks
BG001	Benralizumab 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks
BG002	Placebo	Placebo administered subcutaneously
BG003	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Benra 30 mg q.4 Weeks	Benralizumab administered subcutaneously every 4 weeks	7	72	34	72
EG001	Benra 30 mg q.8 Weeks	Benralizumab administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks	7	73	34	73
EG002	Placebo	Placebo administered subcutaneously	14	75	49	75