Trial Outcomes & Findings for A Study of the Safety and Effectiveness of Benralizumab to Treat Patients With Severe Uncontrolled Asthma. (NCT NCT03170271)

Last Updated: 2021-11-01

Results Overview

An asthma exacerbation was defined as a worsening of asthma that led to any of the following: * Use of systemic corticosteroids (or temporary increase in stable oral corticosteroids \[OCS\] background dose) for at least 3 days; a single depo-injectable dose of corticosteroids was considered equivalent to a 3-day course of systemic corticosteroids. * An emergency room/urgent care visit (defined as evaluation and treatment for \< 24 hours in an emergency department or urgent care center) due to asthma that required systemic corticosteroids (as per above). * An inpatient hospitalization (defined as admission to an inpatient facility and/or evaluation and treatment in a healthcare facility for ≥ 24 hours) due to asthma. Annual exacerbation rate = 365.25\*total number of exacerbations / total duration of follow-up within the treatment group. Annual asthma exacerbation rates over the 24-week period were estimated using a negative binomial model.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

660 participants

Primary outcome timeframe

Baseline (Week 0) up to Week 24

Results posted on

2021-11-01

Participant Flow

Patients with severe uncontrolled asthma and peripheral blood eosinophil counts of ≥150 cells/microliter (μL) (with major subgroups of 150-300 cells/μL plus clinical features and ≥300 cells/μL) were recruited to 221 centers in 14 countries. Patients were randomized in a 2:1 ratio to receive benralizumab or matched placebo for 24 weeks. Results are reported for the double-blind period of the study (data cut-off: 12 Sep 2019).

Severe eosinophilic patients were to have had ≥ 2 asthma exacerbations while on maintenance inhaled corticosteroids (ICS) plus another asthma controller that required treatment with systemic corticosteroids in the 12 months prior to enrolment. Patients continued to receive their standard of care asthma therapy throughout the study period.

Participant milestones

Participant milestones
Measure	Benralizumab Patients received benralizumab 30 milligrams (mg) administered subcutaneously (sc) in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An End of Treatment (EOT) visit was performed at Week 24.	Placebo Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Overall Study STARTED	431	229
Overall Study Received Treatment	427	229
Overall Study COMPLETED	398	218
Overall Study NOT COMPLETED	33	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Benralizumab Patients received benralizumab 30 milligrams (mg) administered subcutaneously (sc) in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An End of Treatment (EOT) visit was performed at Week 24.	Placebo Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Overall Study Adverse Event	7	2
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	1	0
Overall Study Protocol-specified withdrawal criterion	2	1
Overall Study Withdrawal by Subject	17	5
Overall Study Other	2	2
Overall Study Randomized in error	4	0

Baseline Characteristics

A Study of the Safety and Effectiveness of Benralizumab to Treat Patients With Severe Uncontrolled Asthma.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Benralizumab n=427 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=229 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Total n=656 Participants Total of all reporting groups
Age, Continuous	52.5 years STANDARD_DEVIATION 12.69 • n=5 Participants	53.3 years STANDARD_DEVIATION 12.52 • n=7 Participants	52.8 years STANDARD_DEVIATION 12.63 • n=5 Participants
Sex: Female, Male Female	263 Participants n=5 Participants	136 Participants n=7 Participants	399 Participants n=5 Participants
Sex: Female, Male Male	164 Participants n=5 Participants	93 Participants n=7 Participants	257 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	49 Participants n=5 Participants	25 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	318 Participants n=5 Participants	172 Participants n=7 Participants	490 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	60 Participants n=5 Participants	32 Participants n=7 Participants	92 Participants n=5 Participants
Race/Ethnicity, Customized White	314 Participants n=5 Participants	168 Participants n=7 Participants	482 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	35 Participants n=5 Participants	18 Participants n=7 Participants	53 Participants n=5 Participants
Race/Ethnicity, Customized Asian	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Other	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Missing	62 Participants n=5 Participants	33 Participants n=7 Participants	95 Participants n=5 Participants
Screening eosinophil count group (cells/µL) ≥ 150 - < 300	129 Participants n=5 Participants	63 Participants n=7 Participants	192 Participants n=5 Participants
Screening eosinophil count group (cells/µL) ≥ 300	297 Participants n=5 Participants	165 Participants n=7 Participants	462 Participants n=5 Participants
Screening eosinophil count group (cells/µL) Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Baseline eosinophil count group (cells/μL) < 300	146 Participants n=5 Participants	74 Participants n=7 Participants	220 Participants n=5 Participants
Baseline eosinophil count group (cells/μL) ≥ 300 - < 450	105 Participants n=5 Participants	56 Participants n=7 Participants	161 Participants n=5 Participants
Baseline eosinophil count group (cells/μL) ≥ 450	176 Participants n=5 Participants	99 Participants n=7 Participants	275 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) up to Week 24

Population: The FAS included all randomized patients who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study.

Outcome measures

Outcome measures
Measure	Benralizumab n=427 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=229 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Annualized Rate of Asthma Exacerbations Over the Treatment Period (up to Week 24)	0.94 Events/year Interval 0.79 to 1.12	1.86 Events/year Interval 1.54 to 2.24

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: The FAS included all randomized patients who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analysis.

The SGRQ is a 50-item patient-reported outcome instrument which measures the health status of patients with airway obstruction diseases. The questionnaire is divided into 2 parts: part 1 consists of 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; part 2 consists of 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ total score indicates the impact of disease on overall health status and is expressed as a percentage of overall impairment (scores range from 0 to100, with 100 representing worst possible health status and 0 indicating the best possible health status). The least squares (LS) mean change from baseline in SGRQ total score at Week 24 is presented.

Outcome measures

Outcome measures
Measure	Benralizumab n=364 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=204 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Change From Baseline in Saint George Respiratory Questionnaire (SGRQ) Total Score to the EOT (Week 24)	-23.06 Scores on a scale Standard Error 1.00	-14.94 Scores on a scale Standard Error 1.34

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Lung function was assessed by FEV1 which was measured by spirometry. Spirometry was performed by the Investigator or authorized delegate according to American Thoracic Society/European Respiratory Society guidelines. The LS mean change from baseline in pre-BD FEV1 at Week 24 is presented.

Outcome measures

Outcome measures
Measure	Benralizumab n=393 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=213 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Change From Baseline in Pre-Bronchodilator (BD) Forced Expiratory Volume in First Second (FEV1) to the EOT (Week 24)	0.30 Liters (L) Standard Error 0.02	0.14 Liters (L) Standard Error 0.03

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

The ACQ-6 is a shortened version of the ACQ that assesses asthma symptoms (night-time waking, symptoms on waking, activity limitation, shortness of breath and wheezing) and short-acting β-2 receptor agonist use. Patients were asked to recall the status of their asthma during the previous week and respond to the questions of the ACQ-6 on a 7-point scale. Questions are weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score is computed as the mean of the responses from all the items in the questionnaire. Mean scores of ≤0.75 indicated well-controlled asthma, scores between 0.75 and \<1.5 indicated partly-controlled asthma, and a score ≥1.5 indicated not well-controlled asthma. The LS mean change from baseline in ACQ-6 score at Week 24 is presented.

Outcome measures

Outcome measures
Measure	Benralizumab n=393 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=216 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Change From Baseline in Asthma Control Questionnaire 6 (ACQ-6) Score to the EOT (Week 24)	-1.47 Scores on a scale Standard Error 0.06	-1.01 Scores on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline (Week 0) up to Week 24

Population: The FAS included all randomized patients who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study.

Time to first asthma exacerbation was derived as follows: Start date of first asthma exacerbation - Date of randomization + 1. The time to first asthma exacerbation for patients who did not experience an asthma exacerbation during the treatment period was censored at the EOT visit (Week 24) for patients who completed the study. Patients who withdrew from the study or were lost to follow-up before the EOT visit were censored at the last visit date after which an exacerbation could not be assessed. The median time to first asthma exacerbation was not calculated, so the number of patients who experienced an asthma exacerbation is presented for the measured values.

Outcome measures

Outcome measures
Measure	Benralizumab n=427 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=229 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Time to First Asthma Exacerbation (up to Week 24)	123 Participants	107 Participants

SECONDARY outcome

Timeframe: Run-in baseline (from Day -28 to Day 0) and Week 24

Home PEF testing was performed by the patient each morning after awakening and before taking their morning asthma medications, and each evening using a peak flow meter. Measurements were taken at approximately the same time each day and recorded in the Asthma Daily Diary. The maximum of the 3 measurements performed every morning and evening were used in the calculation of the weekly means. A weekly mean was calculated as the sum of all non-missing daily measures over the 7 sequential days divided by the number of non-missing daily measures. If more than 3 daily measures (\> 50%) within a period were missing, then the weekly mean for that period was set to 'missing'. Change from run-in baseline in weekly means for morning PEF and evening PEF are presented. Baseline was the average for data collected over the last 7 days of the run-in period prior to randomization.

Outcome measures

Outcome measures
Measure	Benralizumab n=427 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=229 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Change From Run-in Baseline Home Peak Expiratory Flow (PEF) (Morning and Evening) to the EOT (Week 24) Morning	27.17 L/minute Standard Error 3.98	7.06 L/minute Standard Error 5.49
Change From Run-in Baseline Home Peak Expiratory Flow (PEF) (Morning and Evening) to the EOT (Week 24) Evening	16.47 L/minute Standard Error 4.04	-6.61 L/minute Standard Error 5.54

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

The SF-36v2 is a 36-item survey of functional health and well-being, with a 1 week recall period. The 8-domain profile consists of the following subscales: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. The physical and mental health component summary scores are computed from subscale scores to give a broader metric of physical and mental health-related quality of life. Each domain score, as well as the physical and mental component scores, were scored on a scale from 0-100 (worst health possible to best health possible); higher scores indicate better health status. Norm-based scoring was used to calculate the 8 SF-36v2 subscales and the 2 component scores. The LS mean change from baseline in each of the SF-36 subscale and component summary scores at Week 24 are presented.

Outcome measures

Outcome measures
Measure	Benralizumab n=287 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=169 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Physical functioning	17.76 Scores on a scale Standard Error 1.21	12.42 Scores on a scale Standard Error 1.59
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Role limitations due to physical health	17.62 Scores on a scale Standard Error 1.34	10.82 Scores on a scale Standard Error 1.76
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Bodily pain	6.44 Scores on a scale Standard Error 1.37	3.37 Scores on a scale Standard Error 1.79
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) General health perceptions	12.92 Scores on a scale Standard Error 1.01	7.29 Scores on a scale Standard Error 1.34
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Vitality	12.04 Scores on a scale Standard Error 1.10	6.53 Scores on a scale Standard Error 1.44
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Social functioning	12.44 Scores on a scale Standard Error 1.34	9.32 Scores on a scale Standard Error 1.75
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Role limitations due to emotional problems	8.23 Scores on a scale Standard Error 1.18	5.79 Scores on a scale Standard Error 1.55
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Mental health	5.57 Scores on a scale Standard Error 0.90	3.89 Scores on a scale Standard Error 1.18
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Physical health component summary score	6.09 Scores on a scale Standard Error 0.46	3.77 Scores on a scale Standard Error 0.60
Change From Baseline in Short Form 36-item Health Survey, Version 2 (SF-36v2) to the EOT (Week 24) Mental health component summary score	2.87 Scores on a scale Standard Error 0.48	1.99 Scores on a scale Standard Error 0.64

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: The FAS included all randomized patients who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study.

The PGI-S is a single question asking the patient to rate the overall severity of their symptoms using a 6-point categorical response scale from 0 to 5 where 0=no symptoms and 5=very severe symptoms. Higher scores indicate a worse outcome. Improvement was defined as a PGI-S at EOT (Week 24) better than PGI-S at baseline. Important improvement was defined as PGI-S at baseline = moderate symptoms or severe symptoms or very severe symptoms shifting to PGI-S at EOT = no symptoms or very mild symptoms or mild symptoms. Patients with missing data at the EOT visit who did not complete the study were considered non-responders. For patients who completed the study with missing data at EOT (Week 24), their last evaluable post-baseline score was used to define responder status. The percentage of patients for each of the indicated PGI-S responder categories are presented.

Outcome measures

Outcome measures
Measure	Benralizumab n=345 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=187 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Patient Global Impression of Severity (PGI-S): Responder Status at the EOT (Week 24) Improvement	61.7 Percentage of patients	53.5 Percentage of patients
Patient Global Impression of Severity (PGI-S): Responder Status at the EOT (Week 24) Important improvement	45.5 Percentage of patients	38.0 Percentage of patients

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: The FAS included all randomized patients who received at least 1 dose of IP, irrespective of their protocol adherence and continued participation in the study.

The Investigator (clinician) and the patient were asked separately to rate the degree of change in the overall asthma status compared to the start of treatment, i.e. baseline randomization visit. A 7-point rating scale was used for the CGI-C (rated by Investigator) and PGI-C (rated by patient) where: 1=Very Much Improved; 2=Much Improved; 3=Minimally Improved; 4=No Changes; 5=Minimally Worse; 6=Much Worse, and 7=Very Much Worse. Higher scores indicate a worse outcome. Responder category definitions: Much improved = (Much improved, Very much improved); Very much improved = (Very much improved). Patients with missing data at the EOT visit who did not complete the study were considered non-responders. For patients who completed the study with missing data at EOT (Week 24), their last evaluable post-baseline score was used to define responder status. The percentage of patients for each of the indicated CGI-C and PGI-C responder categories are presented.

Outcome measures

Outcome measures
Measure	Benralizumab n=427 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=229 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Clinician Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C): Responder Status at the EOT (Week 24) CGI-C: Much improved	52.9 Percentage of patients	35.2 Percentage of patients
Clinician Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C): Responder Status at the EOT (Week 24) CGI-C: Very much improved	15.0 Percentage of patients	4.8 Percentage of patients
Clinician Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C): Responder Status at the EOT (Week 24) PGI-C: Much improved	55.9 Percentage of patients	38.2 Percentage of patients
Clinician Global Impression of Change (CGI-C) and Patient Global Impression of Change (PGI-C): Responder Status at the EOT (Week 24) PGI-C: Very much improved	37.7 Percentage of patients	16.7 Percentage of patients

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

For part 1 of the PSIA only administered at baseline, patients reviewed 8 concepts (including cardinal asthma symptoms, activities, awakenings, triggers) and selected those which were typically bothersome. Based on part 1 selections, part 2 of the PSIA produced a rank ordered list of bothersome concepts individualized per the patient for subsequent evaluation. For part 3 of the PSIA assessed at baseline and during the study, patients recorded the severity of each selected symptom or impairment using an 11-point numeric rating scale where: 0=Did not experience and 10=Worst I can imagine. Higher scores indicate a worse outcome. The LS mean change from baseline in PSIA severity score for the indicated categories at Week 24 are presented. A negative change from baseline indicates an improvement in symptoms. Note: Average PSIA was calculated only where all of top 3 ranked symptoms/impairments were available, otherwise average was set to missing.

Outcome measures

Outcome measures
Measure	Benralizumab n=319 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=180 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Change From Baseline in Predominant Symptom and Impairment Assessment (PSIA) Severity Score for Average of Top 3 Ranked Symptoms/Impairments and for Top Ranked Symptom/Impairment at the EOT (Week 24) Average of top 3 ranked	-2.97 Scores on a scale Standard Error 0.14	-1.82 Scores on a scale Standard Error 0.19
Change From Baseline in Predominant Symptom and Impairment Assessment (PSIA) Severity Score for Average of Top 3 Ranked Symptoms/Impairments and for Top Ranked Symptom/Impairment at the EOT (Week 24) Top ranked	-3.02 Scores on a scale Standard Error 0.15	-1.87 Scores on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: The chronic rhinosinusitis with nasal polyposis sub-study analysis set was defined as the subset of patients with doctor-diagnosed chronic rhinosinusitis and nasal polyposis included in their medical history who had signed the informed consent to participate in the sub-study and who had received at least 1 dose of IP.

The 22-item SNOT 22 questionnaire was used to assess the rhinosinusitis health status and quality of life of patients with baseline chronic rhinosinusitis with nasal polyposis. The 22-question SNOT-22 is scored as 0 (no problem) to 5 (problem as bad as it can be) with a total range from 0 to 110. Higher scores indicate poorer outcomes. The LS mean changes from baseline in SNOT-22 total score in patients in the chronic rhinosinusitis with nasal polyposis sub-study analysis set at Week 24 are presented.

Outcome measures

Outcome measures
Measure	Benralizumab n=92 Participants Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=50 Participants Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
Change From Baseline in the Sino-Nasal Outcome Test Item 22 (SNOT-22) Total Score to the EOT (Week 24)	-19.02 Scores on a scale Standard Error 2.27	-10.11 Scores on a scale Standard Error 3.04

Adverse Events

Benralizumab

Serious events: 23 serious events

Other events: 136 other events

Deaths: 0 deaths

Placebo

Serious events: 25 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Benralizumab n=427 participants at risk Patients received benralizumab 30 mg administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.	Placebo n=229 participants at risk Patients received matching placebo solution administered sc in an accessorized pre-filled syringe at Week 0 (initial dose), Week 4 (loading dose), Week 8 and Week 16. An EOT visit was performed at Week 24.
General disorders Pyrexia	6.1% 26/427 • Number of events 29 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	2.2% 5/229 • Number of events 8 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.
Infections and infestations Bronchitis	5.2% 22/427 • Number of events 23 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	7.9% 18/229 • Number of events 22 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.
Infections and infestations Nasopharyngitis	7.0% 30/427 • Number of events 36 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	7.4% 17/229 • Number of events 23 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.
Infections and infestations Sinusitis	6.6% 28/427 • Number of events 32 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	5.2% 12/229 • Number of events 17 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.
Infections and infestations Upper respiratory tract infection	4.0% 17/427 • Number of events 19 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	5.2% 12/229 • Number of events 13 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.
Nervous system disorders Headache	8.7% 37/427 • Number of events 50 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	3.1% 7/229 • Number of events 11 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.
Respiratory, thoracic and mediastinal disorders Cough	3.3% 14/427 • Number of events 16 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	5.7% 13/229 • Number of events 17 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.6% 7/427 • Number of events 9 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.	5.7% 13/229 • Number of events 19 • Adverse event (AE) data is reported for the on-treatment period + follow-up (up to a maximum of 24 weeks). Assessed until 12 Sep 2019 analysis cut-off date. AE definition for on-treatment period: onset date ≥ first dose of IP and ≤ scheduled EOT visit, or IP discontinuation (IPD) visit for patients prematurely discontinuing IP. If both EOT and IPD visits were missing, upper limit of the on-treatment period was defined as day of last dose of IP + 56 days. If upper limit was after end of the on-study period, upper limit was set to end of on-study period.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place