OSTRO: Efficacy and Safety Study of Benralizumab for Patients With Severe Nasal Polyposis

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03401229
• Collaborator: (none)
• Enrollment: 413
• Locations: 99
• Arms: 2
• Actual Duration (Months): 30.5
• Patients Per Site: 4.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The aim of this present study is to investigate the use of benralizumab as treatment for severe nasal polyposis. The effect of benralizumab on nasal polyps will be assessed over a 56 weeks of treatment period in patients with severe bilateral nasal polyposis who are still symptomatic despite standard of care therapy, i.e current use of intranasal corticosteroids (INCS) and prior surgery and/or use of systemic corticosteroids. The first 200 patients that complete the 56-week treatment will have a 6 month follow-up (FU) period without dosing.

Condition or Disease	Intervention/Treatment	Phase
Nasal Polyposis	Biological: Benralizumab 30 mg SC + Mometasone Furoate; Biological: Matching placebo SC + Mometasone Furoate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 413 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study Of Benralizumab in Patients With Severe Nasal Polyposis
• Actual Study Start Date: Jan 15, 2018
• Actual Primary Completion Date: Jul 31, 2020
• Actual Study Completion Date: Jul 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Benralizumab 30mg SC + MF SC - subcutaneously MF - Mometasone Furoate	Biological: Benralizumab 30 mg SC + Mometasone Furoate; Benralizumab injection is 30mg/ml SC clear to opalescent, colourless to yellow solution in accessorized pre-filled syringe. Benralizumab 30 mg SC will be injected every 4 weeks for the first 3 doses - Weeks 0 , 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48. Total of 8 doses. Mometasone Furoate Nasal Spray (MFNS) - intranasal corticosteroid - 2 doses (1 dose = 50 micrograms/actuation) in each nostril twice daily. Total daily dose of 400mcg. MFNS will be used for a minimum of 4 weeks prior to randomization and will be continued throughout the study.
Placebo Comparator: Placebo SC + MF	Biological: Matching placebo SC + Mometasone Furoate; Matching placebo injection is SC clear to opalescent, colourless to yellow solution in accessorized pre-filled syringe. Matching placebo SC will be injected every 4 weeks for the first 3 doses - Weeks 0 , 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48. Total of 8 doses. Mometasone Furoate Nasal Spray (MFNS) - intranasal corticosteroid - 2 doses (1 dose = 50 micrograms/actuation) in each nostril twice daily. Total daily dose of 400mcg. MFNS will be used for a minimum of 4 weeks prior to randomization and will be continued throughout the study.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Total NPS at Week 40 [Baseline to week 40]

   Change from baseline in total nasal polyps score (NPS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The total NPS was the sum of the right and left nostril scores and maximum total NPS is 8, as evaluated by nasal endoscopy and the left and right score were based on central read with scale from 0 to 4 where higher score reflects heavier bilateral nasal polyp burden. Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

2. Change From Baseline in NBS at Week 40 [Baseline to week 40]

   Change from baseline in nasal blockage score (NBS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The NBS was captured by an item in NPSD. Patients were asked to rate the severity of their worst nasal blockage over the past 24 hours using the following response options: 0-none; 1-mild; 2-moderate; 3-severe. The NBS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

Secondary Outcome Measures

1. Change From Baseline in SNOT-22 at Week 40 [Baseline to week 40]

   Change from baseline in SinoNasal outcome test (SNOT-22) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The SNOT-22 is a condition specific health-related quality of life assessment which captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal conditions. The total score is the sum of item scores and has a range from 0 to 110 (higher scores indicate poorer outcomes). Baseline was the last valid value on or prior to the date of randomization. Data collected after NP surgery and/or SCS_NP were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

2. Time to First NP Surgery and/or SCS Use for NP to Week 56 [Baseline to week 56]

   The cumulative percentage and the corresponding 95% CI are based on the Kaplan-Meier estimates. Patients can have more than 1 rescue category during the study, and the first rescue per patient is considered. The time to first nasal polyposis (NP) surgery and/or systemic corticosteroids (SCS) use for NP up to week 56 was calculated based on the earliest occurrence of NP surgery and/or SCS use for NP and was calculated as follows: Time to first NP surgery and/or SCS use for NP = Earlier of (Start date of first NP surgery, Start date of first SCS use for NP) - date of randomization + 1. For patients who did not experience any surgery or SCS use for NP, the time to event was censored at earlier of (date of their week 56 visit, date of discontinuation).

3. Time to the First NP Surgery up to Week 56 [Baseline to week 56]

   The cumulative percentage and the corresponding 95% CI are based on the Kaplan-Meier estimates. Patients can have more than 1 rescue category during the study, and the first rescue per patient is considered. The time to first nasal polyposis (NP) surgery up to week 56 was calculated based on the earliest occurrence of NP surgery and was calculated as follows: Time to first NP surgery=Start date of first NP surgery - date of randomization + 1. For patients who did not experience any surgery, the time to event was censored at earlier of (date of their week 56 visit, date of discontinuation).

4. Change From Baseline in DSS at Week 40 [Baseline to week 40]

   Change from baseline in difficulty with sense of smell (DSS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The DSS is captured by an item in the NPSD. Severity of worst difficulty with sense of smell over the past 24 hours was rated with response options: 0-none; 1-mild; 2-moderate; 3-severe. The DSS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids use for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

5. Change From Baseline in NPS at Week 56 [Baseline to week 56]

   Change from baseline in total nasal polyps score (NPS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The total NPS is the sum of the right and left nostril scores, as evaluated by nasal endoscopy and the left and right score are based on central read with scale from 0 to 4 where higher score reflects heavier bilateral nasal polyp burden. Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

6. Change From Baseline in NBS at Week 56 [Baseline to week 56]

   Change from baseline in nasal blockage score (NBS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The NBS is captured by an item in the NPSD. Patients were asked to rate the severity of their worst nasal blockage over the past 24 hours using the following response options: 0-none; 1-mild; 2-moderate; 3-severe. The NBS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

7. Change From Baseline in SNOT-22 at Week 56 [Baseline to week 56]

   Change from baseline in SinoNasal outcome test (SNOT-22) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The SNOT-22 is a condition specific health-related quality of life assessment which captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal conditions. The total score is range from 0 to 110 (higher scores indicate poorer outcomes). Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

8. Change From Baseline in DSS at Week 56 [Baseline to week 56]

   Change from baseline in difficulty with sense of smell (DSS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The DSS is captured by an item in the NPSD with response options: 0-none; 1-mild; 2-moderate; 3-severe to rate the severity of their worst difficulty with sense of smell over past 24 hours. The DSS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

9. Change From Baseline in LMS at EOT/IPD [Baseline to EOT/IPD, up to 56 weeks]

   Change from baseline in Computed tomography (CT) Lund Mackay Score (LMS) at end of treatment (EOT)/investigational product discontinuation (IPD) was defined as the endpoint value at EOT/IPD minus the baseline value. The LMS evaluates the patency using a 0-2 scale (0-normal; 1-partial opacification; and 2-total opacification) of each sinus (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side). The osteomeatal complex is graded as 0- not occluded or 2-occluded. The total CT score is the sum of the scores from all the sinus and ranges from 0 to 24. The minimum is 0 and higher score indicates worse outcome. The analysis used the data collected after systemic corticosteroids for nasal polyposis (SCS_NP). A composite strategy was used for NP surgery. If a patient had NP surgery before EOT/IPD CT scan, the data was censored after the time of the first NP surgery and the worst possible value (WP) was imputed in its place.

10. Percentage of Subjects With NP Surgery [Baseline to week 56]

    The percentage of patients who had nasal polyposis (NP) surgery or systemic corticosteroids use for nasal polyposis (SCS_NP) surgery up to week 56 was summarized and analyzed using the Cochran-Mantel-Haenszel test stratified by region (US vs non-US) and baseline comorbid asthma status (yes vs no).

11. Percentage of Subjects With SCS_NP [Baseline to week 56]

    The percentage of patients who had systemic corticosteroids (SCS) use for nasal polyposis (NP) surgery up to week 56 was summarized and analyzed using the Cochran-Mantel-Haenszel test stratified by region (US vs non-US) and baseline comorbid asthma status (yes vs no).

12. Percentage of Subjects With NP Surgery or SCS_NP [Baseline to week 56]

    The percentage of patients who had nasal polyposis (NP) surgery or systemic corticosteroids use for nasal polyposis (SCS_NP) surgery up to week 56 was summarized and analyzed using the Cochran-Mantel-Haenszel test stratified by region (US vs non-US) and baseline comorbid asthma status (yes vs no).

13. Time to First SCS_NP up to Week 56 [Baseline to week 56]

    The cumulative percentage and the corresponding 95% CI are based on the Kaplan-Meier estimates. Patients can have more than 1 rescue category during the study, and the first rescue per patient is considered. The time to first systemic corticosteroids for use for nasal polyposis (SCS_NP) up to week 56 was calculated based on the earliest occurrence of SCS_ NP and was calculated as follows: Time to first SCS_NP = Earlier of (Start date of first SCS use for NP) - date of randomization + 1. For patients who did not experience any SCS use for NP, the time to event was censored at earlier of (date of their week 56 visit, date of discontinuation). The time to first SCS use for NP surgery was analyzed using a Cox proportional hazard model with treatment arm, region (US vs non-US) and baseline comorbid asthma status (yes vs no) as covariates. A hazard ratio less than 1 indicates a lower rate of incidence for subjects on benra.

14. Total Number of Courses of SCS for NP [Baseline to week 56]

    The total number of courses of systemic corticosteroids (SCS) use for nasal polyposis (NP) was summarized using descriptive statistics.

15. Total SCS_NP Dose (a) Used (mg) [Baseline to week 56]

    The total systemic corticosteroids (SCS) for nasal polyposis (NP) dose used (mg) was summarized using descriptive statistics.

16. Total Duration of SCS_NP (Days) [Baseline to week 56]

    The total duration of systemic corticosteroids (SCS) for nasal polyposis (NP) in days was summarized using descriptive statistics.

17. Annual SCS_NP Use Rate Comparison by Period, Negative Binomial Model [Baseline to week 56]

    Annual systemic corticosteroids for nasal polyposis (SCS_NP) use rate =365.25×total number of courses of SCS_NP /total duration of follow-up within the treatment group (days). The estimated annual event rates, absolute differences, rate ratio and the corresponding confidence interval were based on a negative binomial model including covariates treatment group, region (US/non-US) and prior use of SCS_NP with total number of courses of SCS_NP as the outcome and the log of each subject's corresponding follow-up time up to week 56 as an offset variable in the model to adjust for subject's having different exposure times during which the events occur.

18. Change From Baseline in TSS at Week 40 [Baseline to week 40]

    Change from baseline in total symptom score (TSS) at week 40 was defined as the endpoint at week 40 minus baseline value. The TSS is defined as sum of first 8 NPSD components. Severity of each nasal symptoms over the past 24 hours is rated using response options: 0-none; 1-mild; 2-moderate; 3-severe. The TSS and the change from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily TSS responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming MAR were used to build the complete imputation datasets for the analysis.

19. Change From Baseline in Difficulty With Sleeping Due to Nasal Symptoms at Week 40 [Baseline to week 40]

    Change from baseline in difficulty with sleeping due to nasal symptoms score at week 40 was defined as the endpoint at week 40 minus baseline value. The score was captured by an item in NPSD. The severity of difficulty with sleeping due to nasal symptoms over past 24 hours was rated using options: 0-none; 1-mild; 2-moderate; 3-severe. The score and change from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis

20. Change From Baseline in Difficulty With Daily Activities Due to Nasal Symptoms at Week 40 [Baseline to week 40]

    Change from baseline in difficulty with daily activities due to nasal symptoms score at week 40 was defined as the endpoint at week 40 minus baseline value. The score was captured by an item in NPSD. The severity of difficulty with daily activities due to nasal symptoms over the past 24 hours was rated using options: 0-none; 1-mild; 2-moderate; 3-severe. The score and change from baseline were summarized every two weeks (bi-weekly). Baseline was average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming MAR were used to build the complete imputation datasets for the analysis.

21. Change From Baseline in UPSIT Score in Males at Week 40 [Baseline to week 40]

    Change from baseline in University of Pennsylvania Smell Identification Test (UPSIT) score at week 40 was defined as the endpoint value at week 40 minus the baseline value. The UPSIT is quantitative test of olfactory function. Scores were based on number of correctly identified odors (score range 0 to 40). Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

22. Change From Baseline in UPSIT Score in Females at Week 40 [Baseline to week 40]

    Change from baseline in University of Pennsylvania Smell Identification Test (UPSIT) score at week 40 was defined as the endpoint value at week 40 minus the baseline value. The UPSIT is quantitative test of olfactory function. Scores are based on number of correctly identified odors (score range 0 to 40). Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.

23. Change From Baseline in Sinus Severity Score at EOT/IPD [Baseline to EOT/IPD, up to 56 weeks]

    Change from baseline in sinus severity score at end of treatment (EOT)/investigational product discontinuation (IPD) was defined as the endpoint value at EOT/IPD minus the baseline value. Quantitative assessment of sinus CT image data was used to derive an objective measure of sinus disease burden called sinus severity score. The sinus severity score is defined as (sinus mucosal volume)/(sinus mucosal volume + sinus air volume)×100. A composite strategy was used for NP surgery. If a patient had NP surgery before EOT/IPD CT scan, the data was censored after the time of the first NP surgery and the worst possible value (WP) was imputed in its place. In calculation of summary statistics (mean and standard deviation), the WP for NP surgery rescued subjects was applied. In ANCOVA, following WP (WP for NP surgery rescued subjects), model included treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status.

24. Change From Baseline in SF-36v2 Physical Component Summary at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 physical component summary (PCS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. PCS score is computed from 8 subscale scores to give a broader metric of physical health-related quality of life. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

25. Change From Baseline in SF-36v2 Mental Component Summary at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 mental component summary (MCS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. MCS score is computed from 8 subscale scores to give a broader metric of mental health-related quality of life. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

26. Change From Baseline in SF-36v2 Physical Functioning at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 physical functioning score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Physical functioning is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

27. Change From Baseline in SF-36v2 Role Limitations Due to Physical Health at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 role limitations due to physical health score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Role limitations due to physical health is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

28. Change From Baseline in SF-36v2 Bodily Pain at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 bodily pain score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Bodily pain is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

29. Change From Baseline in SF-36v2 General Health Perceptions at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 general health perceptions score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. General health perceptions is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing are excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

30. Change From Baseline in SF-36v2 Vitality at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 vitality score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Vitality is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

31. Change From Baseline in SF-36v2 Social Functioning at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 social functioning score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 are used to compute an 8-domain profile of functional health and well-being scores. Social functioning is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

32. Change From Baseline in SF-36v2 Role Limitations Due to Emotional Problems at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 role limitations due to emotional problems score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Role limitations due to emotional problems is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

33. Change From Baseline in SF-36v2 Mental Health at Week 56 [Baseline to week 56]

    Change from baseline in SF-36v2 mental health score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Mental health is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in protocol.

2. Provision of signed and dated, written informed consent form (ICF) prior to any mandatory study specific procedures, sampling, and analyses and according to international guidelines and/or applicable European Union (EU) guidelines.

3. Provision of signed and dated written genetic informed consent in patients that agree to participate in the genetic sampling, prior to collection of sample for genetic analysis.

4. Female or male patients aged 18 to 75 years inclusive, at the time of signing the ICF.

5. Patients with bilateral sinonasal polyposis that, despite treatment with a stable dose of intranasal corticosteroids (INCS) for at least 4 weeks prior to V1, in addition to history of treatment with systemic (SCS -oral, parenteral) or prior surgery for nasal polyposis (NP), have severity consistent with a need for surgery as described by:

• A minimum total Nasal Polyp Score (NPS) of 5 out of a maximum score of 8 (with a unilateral score of at least 2 for each nostril) at V1, and continuously maintained at V2 to meet the randomization criterion, as determined by the study Imaging Core Lab;

• Ongoing symptoms for at least 12 weeks prior to V1;

• Patient-reported moderate to severe nasal blockage score (NBS) 2 or 3 over the 2-weeks prior to V1 (2-week recall assessment of symptoms, scores 0-none to 3-severe).

1. SNOT-22 total score ≥ 30 at enrolment.

Patient must meet the following criteria (points 7-10) at the randomization visit:

1. At least 8 days of evaluable daily diary data in the 14-day period prior to randomization (baseline bi-weekly mean score collected from study Day -13 to study Day 0).

2. At randomization, a bi-weekly mean NBS ≥ 1.5.

3. SNOT-22 total score ≥ 30 at randomization.

4. At least 70% compliance with INCS during the run-in period based on daily diary.

5. Patients with a minimum weight of 40kg.

6. Negative serum pregnancy test result and a negative urine pregnancy test at randomization for female patients of childbearing potential.

7. Women of childbearing potential (WOCBP) must use an effective form of birth control as defined in the Clinical Study Protocol (CSP).

8. Male subjects who are sexually active must be surgically sterile at least one year prior to Visit 1 or must use an adequate method of contraception (condom or condom with spermicide depending on local regulations) from the first dose of IP until 16 weeks after their last dose. Men with a partner or partners who is (are) not of childbearing potential are exempt of these requirements

Exclusion Criteria:

1. Patients who have undergone any nasal and/or sinus surgery within 3 months prior to V1.

2. Patients with conditions or concomitant disease that makes them non evaluable for the co-primary efficacy endpoint such as:

• Unilateral antrochoanal polyps;

• Nasal septal deviation that occludes at least one nostril;

• Acute sinusitis, nasal infection, or upper respiratory infection at screening or in the 2 weeks before screening;

• Current rhinitis medicamentosa;

• Allergic fungal rhinosinusitis (AFRS) or Allergic fungal sinusitis (AFS);

• Nasal cavity tumors.

1. Clinically important comorbidities that could confound interpretation of clinical efficacy results including, but not limited to: active upper or lower respiratory tract infection, cystic fibrosis, primary ciliary dyskinesia, eosinophilic diseases other than asthma (e.g. allergic bronchopulmonary aspergillosis/mycosis, eosinophilic granulomatosis with polyangitis [Churg-Strauss syndrome], hypereosinophilic syndromes), granulomatosis with polyangitis (Wegener's granulomatosis), Young's syndrome, etc.

2. Any disorder, including but not limited to: cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator or AstraZeneca 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.

1. Patients experiencing an asthma exacerbation requiring systemic (oral and/or parenteral) corticosteroids treatment or hospitalization (>24hrs) for treatment of asthma within 4 weeks prior to V1.

2. History of anaphylaxis to any biologic therapy or vaccine.

3. Known history of allergy or reaction to any component of the Investigational Product (IP) formulation.

4. History of Guillain-Barré syndrome.

5. A helminth parasitic infection diagnosed within 24 weeks prior to V1 and has not been treated with, or has failed to respond to standard of care therapy.

6. Current malignancy, or history of malignancy, except for: - Patients who have had basal cell carcinoma, localized squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that patient is in remission and curative therapy was completed at least 12 months prior to V1; - Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to V1.

NOTE: Hormonal therapy is allowed. As long as the cancer is in remission for 5 years, the patient is eligible.

1. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which may put the patient at risk or interfere with study assessments.

2. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology (confirmed by additional testing, e.g. hepatitis C RNA test, if indicated), or a positive medical history for hepatitis B or C (Note: Patients with history of hepatitis B vaccination without history of hepatitis B are allowed to enroll).

3. History of known immunodeficiency disorder, including a positive human immunodeficiency virus (HIV) test.

4. Infection requiring systemic antibiotics (Ab) within 14 days prior to V1

5. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, or any experimental anti-inflammatory therapy) within 3 months prior to V1.

6. Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within 6 months or 5 half-lives prior to the date informed consent, is obtained, whichever is longer, prior to V1 and during the study period. This also applies to patients who previously participated in clinical studies and were treated with monoclonal antibodies (e.g. mepolizumab, reslizumab, dupilumab, omalizumab). Note that this restriction do not apply to patients, who are confirmed to have only received treatment with placebo.

7. Previous receipt of benralizumab.

8. Receipt of immunoglobulin or blood products within 30 days prior to V1.

9. Receipt of live attenuated vaccines 30 days prior to the date of randomization.

10. Receipt of any investigational drug within 30 days or 5 half-lives whichever is longer prior to randomization.

11. Receipt of systemic corticosteroid 4 weeks prior to V1, or a scheduled systemic corticosteroid treatment during the study period.

NOTE: Sustained release steroids (e.g. Kenalog [Triamcinolone acetonide]) or depot injections require minimum 6 weeks washout prior to V1.

1. Receipt of leukotriene antagonist/modifiers for patients who were not on a continuous stable dose for ≥30 days prior to V1.

2. Concurrent enrolment in another clinical drug interventional trial.

3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ 3 times the upper limit of normal (ULN) confirmed during screening period.

4. Previous randomization in the present study.

5. Planned major surgical procedures or scheduled NP surgery at the time of the study enrolment and randomization.

6. Initiated or is being maintained on an aspirin desensitization regimen for the management of aspirin exacerbated respiratory disease (AERD) at the time of study enrolment or during the run-in period.

7. For women only - currently pregnant (or intend to become pregnant), breastfeeding or lactating.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35209
2	Research Site	Fresno	California	United States	93720
3	Research Site	Huntington Beach	California	United States	92647
4	Research Site	La Mesa	California	United States	91942
5	Research Site	Los Angeles	California	United States	90048
6	Research Site	Los Angeles	California	United States	90095-1624
7	Research Site	Orange	California	United States	92868
8	Research Site	Roseville	California	United States	95661
9	Research Site	Walnut Creek	California	United States	94598
10	Research Site	Centennial	Colorado	United States	80112
11	Research Site	Glenwood Springs	Colorado	United States	81601
12	Research Site	Washington	District of Columbia	United States	20037
13	Research Site	Lake Mary	Florida	United States	32746
14	Research Site	Atlanta	Georgia	United States	30308
15	Research Site	Decatur	Georgia	United States	30030
16	Research Site	Chicago	Illinois	United States	60611
17	Research Site	Chicago	Illinois	United States	60657
18	Research Site	Des Moines	Iowa	United States	50312
19	Research Site	Kansas City	Kansas	United States	66160
20	Research Site	Louisville	Kentucky	United States	40220
21	Research Site	Baltimore	Maryland	United States	21224
22	Research Site	Boston	Massachusetts	United States	02111
23	Research Site	Boston	Massachusetts	United States	02114
24	Research Site	Rochester	Minnesota	United States	55905
25	Research Site	Lincoln	Nebraska	United States	68510
26	Research Site	Bronx	New York	United States	10461
27	Research Site	Hewlett	New York	United States	11557
28	Research Site	New Windsor	New York	United States	12553
29	Research Site	New York	New York	United States	10001
30	Research Site	New York	New York	United States	10011
31	Research Site	New York	New York	United States	10016
32	Research Site	New York	New York	United States	10022
33	Research Site	New York	New York	United States	10075
34	Research Site	New York	New York	United States	10128
35	Research Site	Plainview	New York	United States	11803
36	Research Site	White Plains	New York	United States	10605
37	Research Site	Charlotte	North Carolina	United States	28210
38	Research Site	Winston-Salem	North Carolina	United States	27103
39	Research Site	Oklahoma City	Oklahoma	United States	73120
40	Research Site	Philadelphia	Pennsylvania	United States	19107
41	Research Site	Pittsburgh	Pennsylvania	United States	15213
42	Research Site	Charleston	South Carolina	United States	29425
43	Research Site	Conroe	Texas	United States	77304
44	Research Site	Houston	Texas	United States	77030
45	Research Site	North Logan	Utah	United States	84341
46	Research Site	Norfolk	Virginia	United States	23507
47	Research Site	Richmond	Virginia	United States	23235
48	Research Site	Spokane	Washington	United States	99201
49	Research Site	Graz		Austria	8036
50	Research Site	Linz		Austria	4010
51	Research Site	Salzburg		Austria	5020
52	Research Site	St. Pölten		Austria	3100
53	Research Site	Wien		Austria	1090
54	Research Site	Bruxelles		Belgium	1200
55	Research Site	Gent		Belgium	9000
56	Research Site	Leuven		Belgium	3000
57	Research Site	Vancouver	British Columbia	Canada	V5Z 1M9
58	Research Site	Hamilton	Ontario	Canada	L8S 1G5
59	Research Site	London	Ontario	Canada	N6A 4V2
60	Research Site	Mississauga	Ontario	Canada	L5A 3V4
61	Research Site	Ottawa	Ontario	Canada	K1G 6C6
62	Research Site	Montreal	Quebec	Canada	H2X 3E4
63	Research Site	Montreal	Quebec	Canada	H3G 1L5
64	Research Site	Montreal	Quebec	Canada	H4A 3J1
65	Research Site	Trois-Rivières	Quebec	Canada	G8T 7A1
66	Research Site	Quebec		Canada	G1V 4G5
67	Research Site	Quebec		Canada	G1V 4W2
68	Research Site	Aalborg		Denmark	9000
69	Research Site	Aarhus N		Denmark	8200
70	Research Site	Hillerød		Denmark	3400
71	Research Site	Hvidovre		Denmark	2650
72	Research Site	København NV		Denmark	2400
73	Research Site	Køge		Denmark	4600
74	Research Site	Næstved		Denmark	4700
75	Research Site	Odense C		Denmark	5000
76	Research Site	Vejle		Denmark	7100
77	Research Site	Aschaffenburg		Germany	63739
78	Research Site	Berlin		Germany	13353
79	Research Site	Dreieich		Germany	63303
80	Research Site	Dresden		Germany	01307
81	Research Site	Düsseldorf		Germany	40225
82	Research Site	Göttingen		Germany	37073
83	Research Site	Heidelberg		Germany	69120
84	Research Site	Lübeck		Germany	23538
85	Research Site	Münster		Germany	48149
86	Research Site	Wiesbaden		Germany	65183
87	Research Site	Budapest		Hungary	1083
88	Research Site	Budapest		Hungary	1106
89	Research Site	Debrecen		Hungary	4032
90	Research Site	Eger		Hungary	3300
91	Research Site	Nyíregyháza		Hungary	4400
92	Research Site	Pécs		Hungary	7621
93	Research Site	Veszprém		Hungary	8200
94	Research Site	Nadarzyn		Poland	05-830
95	Research Site	Strzelce Opolskie		Poland	47-100
96	Research Site	Warszawa		Poland	02-547
97	Research Site	Wrocław		Poland	50-220
98	Research Site	Wrocław		Poland	53-301
99	Research Site	Łódź		Poland	90-153

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Claus Bachert, Prof. dr. h.c., University Hospital Ghent, de Pintelaan 185, 9000 Ghent, Belgium

Study Documents (Full-Text)

• Study Protocol - Aug 5, 2020
• Statistical Analysis Plan - Aug 19, 2020

More Information

Additional Information:

• The redacted CSP.
• The redacted SAP.

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT03401229
• Other Study ID Numbers: D3252C00001; 2017-003675-61; NCT03627286
• First Posted: Jan 17, 2018
• Last Update Posted: Oct 12, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by AstraZeneca: Polyps; Nasal polyps; Nasal polyposis; Nose diseases; Respiratory tract diseases; Otorhinolaryngologic diseases; Benralizumab; Mometasone furoate
• Additional relevant MeSH terms: Colorectal Neoplasms; Nasopharyngeal Neoplasms; Nasal Polyps; Mometasone Furoate; Benralizumab

Study Results

Participant Flow

Recruitment Details	413 participants were randomized to receive treatment in study D3250C00001 (OSTRO) with benralizumab 30 mg or placebo. Of the 413 patients randomized, 410 (99.3%) received treatment with study drug. 207 (50.5%) patients received benralizumab 30 mg and 203 (49.5%) patients received placebo
Pre-assignment Detail	In OSTRO, at the first visit, ie, the enrollment visit 1, patients were evaluated regarding the protocol mandated inclusion and exclusion criteria. After enrolment, eligible patients entered a 5-week screening/run in period on a stable dose of study provided Mometasone Furoate Nasal Spray (MFNS).

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Period Title: Overall Study
STARTED	207	203
COMPLETED	167	166
NOT COMPLETED	40	37

Baseline Characteristics

Arm/Group Title	Benra 30 mg	Placebo	Total
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Total of all reporting groups
Overall Participants	207	203	410
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	50.1 (12.38)	50.2 (13.91)	50.2 (13.14)
Sex: Female, Male (Count of Participants)
Female	65 31.4%	82 40.4%	147 35.9%
Male	142 68.6%	121 59.6%	263 64.1%
Race/Ethnicity, Customized (Number) [Number]
White	197 95.2%	190 93.6%	387 94.4%
Black or African American	4 1.9%	8 3.9%	12 2.9%
American Indian or Alaska Native	0 0%	1 0.5%	1 0.2%
Native Hawaiian or Other Pacific Islander	1 0.5%	0 0%	1 0.2%
Asian	3 1.4%	1 0.5%	4 1%
Other	2 1%	3 1.5%	5 1.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Total NPS at Week 40
Description	Change from baseline in total nasal polyps score (NPS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The total NPS was the sum of the right and left nostril scores and maximum total NPS is 8, as evaluated by nasal endoscopy and the left and right score were based on central read with scale from 0 to 4 where higher score reflects heavier bilateral nasal polyp burden. Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	187	187
Mean (Standard Deviation) [Score on a scale]	-0.36 (1.66)	0.17 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	The primary analysis compared the changes from baseline of benralizumab with placebo. H0: The change from baseline in total NPS and/or the change from baseline in NBS are similar between benralizumab and placebo. H1: Both of the change from baseline in total NPS and the change from baseline in NBS are different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	To account for multiplicity, a pre-specified testing strategy was followed to control the overall type I error rate. Both of the co-primary endpoints were tested at 0.01 (two-sided).
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.570
	Confidence Interval	(2-Sided) 95%; -0.852 to -0.289
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in NBS at Week 40
Description	Change from baseline in nasal blockage score (NBS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The NBS was captured by an item in NPSD. Patients were asked to rate the severity of their worst nasal blockage over the past 24 hours using the following response options: 0-none; 1-mild; 2-moderate; 3-severe. The NBS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	181
Mean (Standard Deviation) [Score on a scale]	-0.68 (1.02)	-0.41 (0.89)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	The primary analysis compared the changes from baseline of benralizumab with placebo. H0: The change from baseline in total NPS and/or the change from baseline in NBS are similar between benralizumab and placebo. H1: Both of the change from baseline in total NPS and the change from baseline in NBS are different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0048
	Comments	To account for multiplicity, a pre-specified testing strategy was followed to control the overall type I error rate. Both of the co-primary endpoints were tested at 0.01 (two-sided).
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.270
	Confidence Interval	(2-Sided) 95%; -0.458 to -0.083
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in SNOT-22 at Week 40
Description	Change from baseline in SinoNasal outcome test (SNOT-22) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The SNOT-22 is a condition specific health-related quality of life assessment which captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal conditions. The total score is the sum of item scores and has a range from 0 to 110 (higher scores indicate poorer outcomes). Baseline was the last valid value on or prior to the date of randomization. Data collected after NP surgery and/or SCS_NP were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	193	190
Mean (Standard Deviation) [Score on a scale]	-15.2 (30.47)	-10.7 (31.64)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline of benralizumab with placebo. H0: The change from baseline in SNOT-22 total score is similar between benralizumab and placebo. H1: The change from baseline in SNOT-22 total score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0821
	Comments	Since both primary endpoints were significant at significant level of 0.01 level, this endpoint was tested at significant level of 0.05.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-5.212
	Confidence Interval	(2-Sided) 95%; -11.087 to 0.664
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Time to First NP Surgery and/or SCS Use for NP to Week 56
Description	The cumulative percentage and the corresponding 95% CI are based on the Kaplan-Meier estimates. Patients can have more than 1 rescue category during the study, and the first rescue per patient is considered. The time to first nasal polyposis (NP) surgery and/or systemic corticosteroids (SCS) use for NP up to week 56 was calculated based on the earliest occurrence of NP surgery and/or SCS use for NP and was calculated as follows: Time to first NP surgery and/or SCS use for NP = Earlier of (Start date of first NP surgery, Start date of first SCS use for NP) - date of randomization + 1. For patients who did not experience any surgery or SCS use for NP, the time to event was censored at earlier of (date of their week 56 visit, date of discontinuation).
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Number of patients analyzed is number of patients who had NP surgery and/or SCS use.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Number (95% Confidence Interval) [months]	35.5	46.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the rate of incidence of first NP surgery and/or SCS use for NP between benralizumab and placebo. H0: The rate is similar between benralizumab and placebo. H1: the rate is different between benralizumab and placebo. Hazard ratio is benralizumab vs placebo and HR less than 1 indicates longer time to event
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0660
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal because test for change from baseline in SNOT-22 at week 40 was not statistically significant.
	Method	Regression, Cox
	Comments	A Cox proportional hazards model including covariates treatment group, region (US/Non-US) and baseline comorbid asthma status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Time to the First NP Surgery up to Week 56
Description	The cumulative percentage and the corresponding 95% CI are based on the Kaplan-Meier estimates. Patients can have more than 1 rescue category during the study, and the first rescue per patient is considered. The time to first nasal polyposis (NP) surgery up to week 56 was calculated based on the earliest occurrence of NP surgery and was calculated as follows: Time to first NP surgery=Start date of first NP surgery - date of randomization + 1. For patients who did not experience any surgery, the time to event was censored at earlier of (date of their week 56 visit, date of discontinuation).
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Number of patients analyzed is number of patients who had NP surgery.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Number (95% Confidence Interval) [months]	16.6	19.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	The endpoint compared the rate of incidence of first NP surgery between benralizumab and placebo. H0: The rate is similar between benralizumab and placebo. H1: the rate is different between benralizumab and placebo. Hazard ratio (HR) is benralizumab vs placebo and HR less than 1 indicates longer time to event
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5008
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal.
	Method	Regression, Cox
	Comments	A Cox proportional hazards model including covariates treatment group, region (US/Non-US) and baseline comorbid asthma status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in DSS at Week 40
Description	Change from baseline in difficulty with sense of smell (DSS) at week 40 was defined as the endpoint value at week 40 minus the baseline value. The DSS is captured by an item in the NPSD. Severity of worst difficulty with sense of smell over the past 24 hours was rated with response options: 0-none; 1-mild; 2-moderate; 3-severe. The DSS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids use for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	181
Mean (Standard Deviation) [Score on a scale]	-0.34 (0.74)	-0.16 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline DSS score of benralizumab with placebo. H0: The change from baseline in DSS score is similar between benralizumab and placebo. H1: The change from baseline in DSS score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0029
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.218
	Confidence Interval	(2-Sided) 95%; -0.361 to -0.074
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in NPS at Week 56
Description	Change from baseline in total nasal polyps score (NPS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The total NPS is the sum of the right and left nostril scores, as evaluated by nasal endoscopy and the left and right score are based on central read with scale from 0 to 4 where higher score reflects heavier bilateral nasal polyp burden. Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	161	171
Mean (Standard Deviation) [Score on a scale]	-0.22 (1.76)	0.18 (1.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline of benralizumab with placebo. H0: The change from baseline in NPS is similar between benralizumab and placebo. H1: The change from baseline in NPS is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0054
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.475
	Confidence Interval	(2-Sided) 95%; -0.810 to -0.141
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in NBS at Week 56
Description	Change from baseline in nasal blockage score (NBS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The NBS is captured by an item in the NPSD. Patients were asked to rate the severity of their worst nasal blockage over the past 24 hours using the following response options: 0-none; 1-mild; 2-moderate; 3-severe. The NBS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	179	175
Mean (Standard Deviation) [Score on a scale]	-0.68 (1.03)	-0.38 (0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline of benralizumab with placebo. H0: The change from baseline in NBS is similar between benralizumab and placebo. H1: The change from baseline in NBS is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0032
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.287
	Confidence Interval	(2-Sided) 95%; -0.477 to -0.096
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in SNOT-22 at Week 56
Description	Change from baseline in SinoNasal outcome test (SNOT-22) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The SNOT-22 is a condition specific health-related quality of life assessment which captures patient-reported physical problems, functional limitations, and emotional consequences of sinonasal conditions. The total score is range from 0 to 110 (higher scores indicate poorer outcomes). Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	190	184
Mean (Standard Deviation) [Score on a scale]	-15.1 (33.55)	-7.9 (33.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline of benralizumab with placebo. H0: The change from baseline in SNOT-22 total score is similar between benralizumab and placebo. H1: The change from baseline in SNOT-22 total score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0188
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-7.492
	Confidence Interval	(2-Sided) 95%; -13.741 to -1.243
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in DSS at Week 56
Description	Change from baseline in difficulty with sense of smell (DSS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The DSS is captured by an item in the NPSD with response options: 0-none; 1-mild; 2-moderate; 3-severe to rate the severity of their worst difficulty with sense of smell over past 24 hours. The DSS and the changes from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	179	175
Mean (Standard Deviation) [Score on a scale]	-0.39 (0.79)	-0.21 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline DSS score of benralizumab with placebo. H0: The change from baseline in DSS score is similar between benralizumab and placebo. H1: The change from baseline in DSS score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0023
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.237
	Confidence Interval	(2-Sided) 95%; -0.389 to -0.084
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in LMS at EOT/IPD
Description	Change from baseline in Computed tomography (CT) Lund Mackay Score (LMS) at end of treatment (EOT)/investigational product discontinuation (IPD) was defined as the endpoint value at EOT/IPD minus the baseline value. The LMS evaluates the patency using a 0-2 scale (0-normal; 1-partial opacification; and 2-total opacification) of each sinus (maxillary, anterior ethmoid, posterior ethmoid, sphenoid, frontal sinus on each side). The osteomeatal complex is graded as 0- not occluded or 2-occluded. The total CT score is the sum of the scores from all the sinus and ranges from 0 to 24. The minimum is 0 and higher score indicates worse outcome. The analysis used the data collected after systemic corticosteroids for nasal polyposis (SCS_NP). A composite strategy was used for NP surgery. If a patient had NP surgery before EOT/IPD CT scan, the data was censored after the time of the first NP surgery and the worst possible value (WP) was imputed in its place.
Time Frame	Baseline to EOT/IPD, up to 56 weeks

Outcome Measure Data

Analysis Population Description

CT analysis set and patients with a baseline CT who are rescued by SCS_NP by week 56

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	81	84
Mean (Standard Deviation) [Score on a scale]	-0.93 (5.06)	-0.20 (4.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline LMS score of benralizumab with placebo. H0: The change from baseline in LMS score is similar between benralizumab and placebo. H1: The change from baseline in LMS score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2375
	Comments	Based on pre-specified testing strategy, this endpoint was not tested for statistical significance and the p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following WP (WP for NP surgery), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.856
	Confidence Interval	(2-Sided) 95%; -2.281 to 0.570
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Percentage of Subjects With NP Surgery
Description	The percentage of patients who had nasal polyposis (NP) surgery or systemic corticosteroids use for nasal polyposis (SCS_NP) surgery up to week 56 was summarized and analyzed using the Cochran-Mantel-Haenszel test stratified by region (US vs non-US) and baseline comorbid asthma status (yes vs no).
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Count of Participants [Participants]	33 15.9%	37 18.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the proportion of subjects with NP surgery between benralizumab and placebo. H0: The proportion is similar between benralizumab and placebo. H1: The proportion is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5419
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	Cochran-Mantel-Haenszel
	Comments	The odds ratio estimate was obtained from the Cochran-Mantel-Haenszel test controlling for region (US/non-US) and baseline comorbid asthma status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.51 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Percentage of Subjects With SCS_NP
Description	The percentage of patients who had systemic corticosteroids (SCS) use for nasal polyposis (NP) surgery up to week 56 was summarized and analyzed using the Cochran-Mantel-Haenszel test stratified by region (US vs non-US) and baseline comorbid asthma status (yes vs no).
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Count of Participants [Participants]	52 25.1%	66 32.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the proportion of subjects with SCS_NP between benralizumab and placebo. H0: The proportion is similar between benralizumab and placebo. H1: The proportion is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0913
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	Cochran-Mantel-Haenszel
	Comments	The odds ratio estimate was obtained from the Cochran-Mantel-Haenszel test controlling for region (US/non-US) and baseline comorbid asthma status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Subjects With NP Surgery or SCS_NP
Description	The percentage of patients who had nasal polyposis (NP) surgery or systemic corticosteroids use for nasal polyposis (SCS_NP) surgery up to week 56 was summarized and analyzed using the Cochran-Mantel-Haenszel test stratified by region (US vs non-US) and baseline comorbid asthma status (yes vs no).
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Count of Participants [Participants]	72 34.8%	91 44.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the proportion of subjects with NP surgery or SCS_NP between benralizumab and placebo. H0: The proportion is similar between benralizumab and placebo. H1: The proportion is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0362
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	Cochran-Mantel-Haenszel
	Comments	The odds ratio estimate was obtained from the Cochran-Mantel-Haenszel test controlling for region (US/non-US) and baseline comorbid asthma status.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.44 to 0.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Time to First SCS_NP up to Week 56
Description	The cumulative percentage and the corresponding 95% CI are based on the Kaplan-Meier estimates. Patients can have more than 1 rescue category during the study, and the first rescue per patient is considered. The time to first systemic corticosteroids for use for nasal polyposis (SCS_NP) up to week 56 was calculated based on the earliest occurrence of SCS_ NP and was calculated as follows: Time to first SCS_NP = Earlier of (Start date of first SCS use for NP) - date of randomization + 1. For patients who did not experience any SCS use for NP, the time to event was censored at earlier of (date of their week 56 visit, date of discontinuation). The time to first SCS use for NP surgery was analyzed using a Cox proportional hazard model with treatment arm, region (US vs non-US) and baseline comorbid asthma status (yes vs no) as covariates. A hazard ratio less than 1 indicates a lower rate of incidence for subjects on benra.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Number (95% Confidence Interval) [months]	25.7	33.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	The endpoint compared the rate of incidence of SCS_NP use between benralizumab and placebo. H0: The rate is similar between benralizumab and placebo. H1: the rate is different between benralizumab and placebo. Hazard ratio (HR) is benralizumab vs placebo and HR less than 1 indicates longer time to event
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1505
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	Regression, Cox
	Comments	A Cox proportional hazards model including covariates treatment group, region (US/Non-US) and baseline comorbid asthma status.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Total Number of Courses of SCS for NP
Description	The total number of courses of systemic corticosteroids (SCS) use for nasal polyposis (NP) was summarized using descriptive statistics.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Mean (Standard Deviation) [number of courses]	1.7 (0.93)	1.6 (0.89)

17. Secondary Outcome

Title	Total SCS_NP Dose (a) Used (mg)
Description	The total systemic corticosteroids (SCS) for nasal polyposis (NP) dose used (mg) was summarized using descriptive statistics.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Mean (Standard Deviation) [milligrams]	1083.2 (4044.29)	435.2 (441.57)

18. Secondary Outcome

Title	Total Duration of SCS_NP (Days)
Description	The total duration of systemic corticosteroids (SCS) for nasal polyposis (NP) in days was summarized using descriptive statistics.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Mean (Standard Deviation) [days]	17.6 (12.45)	20.1 (34.68)

19. Secondary Outcome

Title	Annual SCS_NP Use Rate Comparison by Period, Negative Binomial Model
Description	Annual systemic corticosteroids for nasal polyposis (SCS_NP) use rate =365.25×total number of courses of SCS_NP /total duration of follow-up within the treatment group (days). The estimated annual event rates, absolute differences, rate ratio and the corresponding confidence interval were based on a negative binomial model including covariates treatment group, region (US/non-US) and prior use of SCS_NP with total number of courses of SCS_NP as the outcome and the log of each subject's corresponding follow-up time up to week 56 as an offset variable in the model to adjust for subject's having different exposure times during which the events occur.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	207	203
Mean (95% Confidence Interval) [number of courses for each patient]	0.40	0.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	The endpoint compared the rate of SCS_NP use between benralizumab and placebo. H0: The rate is similar between benralizumab and placebo. H1: the rate is different between benralizumab and placebo. Rate ratio is benralizumab vs placebo and Rate ratio less than 1 indicates less likely of SCS_NP use.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2189
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	Negative Bionomial Model
	Comments	Model included treatment, US/non-US and prior use of SCS_NP with total number of courses of SCS_NP as outcome and log of follow-up time as an offset
Method of Estimation	Estimation Parameter	Rate Ratio
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Change From Baseline in TSS at Week 40
Description	Change from baseline in total symptom score (TSS) at week 40 was defined as the endpoint at week 40 minus baseline value. The TSS is defined as sum of first 8 NPSD components. Severity of each nasal symptoms over the past 24 hours is rated using response options: 0-none; 1-mild; 2-moderate; 3-severe. The TSS and the change from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily TSS responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming MAR were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	181
Mean (Standard Deviation) [Score on a scale]	-3.20 (6.90)	-1.38 (6.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline score between benralizumab and placebo. H0: The change from baseline score is similar between benralizumab and placebo. H1: The change from baseline score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0036
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-1.854
	Confidence Interval	(2-Sided) 95%; -3.101 to -0.608
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Change From Baseline in Difficulty With Sleeping Due to Nasal Symptoms at Week 40
Description	Change from baseline in difficulty with sleeping due to nasal symptoms score at week 40 was defined as the endpoint at week 40 minus baseline value. The score was captured by an item in NPSD. The severity of difficulty with sleeping due to nasal symptoms over past 24 hours was rated using options: 0-none; 1-mild; 2-moderate; 3-severe. The score and change from baseline were summarized every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	181
Mean (Standard Deviation) [Score on a scale]	-0.39 (1.06)	-0.19 (1.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline score between benralizumab and placebo. H0: The change from baseline score is similar between benralizumab and placebo. H1: The change from baseline score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0941
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.166
	Confidence Interval	(2-Sided) 95%; -0.360 to 0.028
	Parameter Dispersion	Type: Value:
	Estimation Comments

22. Secondary Outcome

Title	Change From Baseline in Difficulty With Daily Activities Due to Nasal Symptoms at Week 40
Description	Change from baseline in difficulty with daily activities due to nasal symptoms score at week 40 was defined as the endpoint at week 40 minus baseline value. The score was captured by an item in NPSD. The severity of difficulty with daily activities due to nasal symptoms over the past 24 hours was rated using options: 0-none; 1-mild; 2-moderate; 3-severe. The score and change from baseline were summarized every two weeks (bi-weekly). Baseline was average of daily responses from Day -13 to Day 1. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming MAR were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	181
Mean (Standard Deviation) [Score on a scale]	-0.35 (1.04)	-0.11 (0.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline score between benralizumab and placebo. H0: The change from baseline score is similar between benralizumab and placebo. H1: The change from baseline score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0246
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.213
	Confidence Interval	(2-Sided) 95%; -0.399 to -0.027
	Parameter Dispersion	Type: Value:
	Estimation Comments

23. Secondary Outcome

Title	Change From Baseline in UPSIT Score in Males at Week 40
Description	Change from baseline in University of Pennsylvania Smell Identification Test (UPSIT) score at week 40 was defined as the endpoint value at week 40 minus the baseline value. The UPSIT is quantitative test of olfactory function. Scores were based on number of correctly identified odors (score range 0 to 40). Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	109	89
Mean (Standard Deviation) [Score on a scale]	-0.20 (10.29)	0.09 (8.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline score between benralizumab and placebo. H0: The change from baseline score is similar between benralizumab and placebo. H1: The change from baseline score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5833
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.672
	Confidence Interval	(2-Sided) 95%; -1.730 to 3.074
	Parameter Dispersion	Type: Value:
	Estimation Comments

24. Secondary Outcome

Title	Change From Baseline in UPSIT Score in Females at Week 40
Description	Change from baseline in University of Pennsylvania Smell Identification Test (UPSIT) score at week 40 was defined as the endpoint value at week 40 minus the baseline value. The UPSIT is quantitative test of olfactory function. Scores are based on number of correctly identified odors (score range 0 to 40). Baseline was the last valid value on or prior to the date of randomization. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for nasal polyposis (SCS_NP) were set to missing. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied. In ANCOVA, a hybrid method of the WP after NP surgery, WOCF after SCS_NP and multiple imputation (MI) assuming missing at random were used to build the complete imputation datasets for the analysis.
Time Frame	Baseline to week 40

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	53	74
Mean (Standard Deviation) [Score on a scale]	1.66 (8.86)	-1.32 (7.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline score between benralizumab and placebo. H0: The change from baseline score is similar between benralizumab and placebo. H1: The change from baseline score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0619
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	ANCOVA
	Comments	ANCOVA following hybrid WP/WOCF and MI (assuming MAR), adjusting for treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	2.684
	Confidence Interval	(2-Sided) 95%; -0.134 to 5.502
	Parameter Dispersion	Type: Value:
	Estimation Comments

25. Secondary Outcome

Title	Change From Baseline in Sinus Severity Score at EOT/IPD
Description	Change from baseline in sinus severity score at end of treatment (EOT)/investigational product discontinuation (IPD) was defined as the endpoint value at EOT/IPD minus the baseline value. Quantitative assessment of sinus CT image data was used to derive an objective measure of sinus disease burden called sinus severity score. The sinus severity score is defined as (sinus mucosal volume)/(sinus mucosal volume + sinus air volume)×100. A composite strategy was used for NP surgery. If a patient had NP surgery before EOT/IPD CT scan, the data was censored after the time of the first NP surgery and the worst possible value (WP) was imputed in its place. In calculation of summary statistics (mean and standard deviation), the WP for NP surgery rescued subjects was applied. In ANCOVA, following WP (WP for NP surgery rescued subjects), model included treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status.
Time Frame	Baseline to EOT/IPD, up to 56 weeks

Outcome Measure Data

Analysis Population Description

CT analysis set and patients with a baseline CT who are rescued by SCS_NP by week 56. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	86	84
Mean (Standard Deviation) [Score on a scale]	-3.48 (24.24)	0.79 (17.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Benra 30 mg, Placebo
	Comments	This endpoint compared the changes from baseline score between benralizumab and placebo. H0: The change from baseline score is similar between benralizumab and placebo. H1: The change from baseline score is different between benralizumab and placebo.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1020
	Comments	This endpoint was not a part of the pre-specified testing strategy and was not tested for statistical significance. The p-value was considered nominal.
	Method	ANCOVA
	Comments	Following WP (WP for NP surgery rescued subjects), model included treatment, baseline score, region (US/Non-US) and baseline comorbid asthma status
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-5.057
	Confidence Interval	(2-Sided) 95%; -11.129 to 1.015
	Parameter Dispersion	Type: Value:
	Estimation Comments

26. Secondary Outcome

Title	Change From Baseline in SF-36v2 Physical Component Summary at Week 56
Description	Change from baseline in SF-36v2 physical component summary (PCS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. PCS score is computed from 8 subscale scores to give a broader metric of physical health-related quality of life. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	-1.557 (17.7075)	-3.185 (17.4189)

27. Secondary Outcome

Title	Change From Baseline in SF-36v2 Mental Component Summary at Week 56
Description	Change from baseline in SF-36v2 mental component summary (MCS) at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. MCS score is computed from 8 subscale scores to give a broader metric of mental health-related quality of life. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	-2.263 (18.4094)	-4.182 (19.3697)

28. Secondary Outcome

Title	Change From Baseline in SF-36v2 Physical Functioning at Week 56
Description	Change from baseline in SF-36v2 physical functioning score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Physical functioning is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	0.080 (14.8681)	-0.911 (14.6581)

29. Secondary Outcome

Title	Change From Baseline in SF-36v2 Role Limitations Due to Physical Health at Week 56
Description	Change from baseline in SF-36v2 role limitations due to physical health score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Role limitations due to physical health is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	1.576 (13.4610)	0.025 (13.3886)

30. Secondary Outcome

Title	Change From Baseline in SF-36v2 Bodily Pain at Week 56
Description	Change from baseline in SF-36v2 bodily pain score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Bodily pain is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	0.982 (15.0935)	-1.066 (15.3689)

31. Secondary Outcome

Title	Change From Baseline in SF-36v2 General Health Perceptions at Week 56
Description	Change from baseline in SF-36v2 general health perceptions score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. General health perceptions is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing are excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	0.445 (14.2295)	-1.064 (13.6387)

32. Secondary Outcome

Title	Change From Baseline in SF-36v2 Vitality at Week 56
Description	Change from baseline in SF-36v2 vitality score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Vitality is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	1.913 (12.9999)	-0.594 (13.5861)

33. Secondary Outcome

Title	Change From Baseline in SF-36v2 Social Functioning at Week 56
Description	Change from baseline in SF-36v2 social functioning score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 are used to compute an 8-domain profile of functional health and well-being scores. Social functioning is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	0.262 (15.1786)	-1.247 (15.9512)

34. Secondary Outcome

Title	Change From Baseline in SF-36v2 Role Limitations Due to Emotional Problems at Week 56
Description	Change from baseline in SF-36v2 role limitations due to emotional problems score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Role limitations due to emotional problems is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	-0.492 (17.1261)	-1.825 (16.6618)

35. Secondary Outcome

Title	Change From Baseline in SF-36v2 Mental Health at Week 56
Description	Change from baseline in SF-36v2 mental health score at week 56 was defined as the endpoint value at week 56 minus the baseline value. The Short Form 36-item Health survey (SF-36v2) is a 36-item, self-report survey of functional health and wellbeing, with 4-week recall period. Responses to SF-36v2 were used to compute an 8-domain profile of functional health and well-being scores. Mental health is one of the 8-domain profile. Data collected after nasal polyposis (NP) surgery and/or systemic corticosteroids for NP (SCS_NP) were set to missing. Non-rescued patients whose post-baseline observations were all missing were excluded from this analysis. In calculation of summary statistics (mean and standard deviation), the worst-possible (WP) after NP surgery and worst-observation carried forward (WOCF) after SCS_NP were applied.
Time Frame	Baseline to week 56

Outcome Measure Data

Analysis Population Description

Full analysis set: All patients randomized and receiving any IP are included in the full analysis set (FAS), irrespective of their protocol adherence and continued participation in the study. Patients are analyzed according to their randomized treatment. Patients who had not been rescued and whose post-baseline observation was missing at the timepoint of interest are excluded from this analysis.

Arm/Group Title	Benra 30 mg	Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.	Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
Measure Participants	191	185
Mean (Standard Deviation) [Score on a scale]	-1.506 (16.5930)	-3.308 (17.2382)

Adverse Events

Time Frame	From first dose of study drug until end of study, up to 603 days.
Adverse Event Reporting Description	For analysis of Adverse Events Safety analysis set is used. Safety analysis set : All randomized participants who received at least one dose of study drug.
Arm/Group Title	Benra 30 mg		Placebo
Arm/Group Description	Benra administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.		Placebo administered every 4 weeks for the first 3 doses - Weeks 0, 4 and 8 and every 8 weeks thereafter - Weeks 16, 24, 32, 40 and 48.
All Cause Mortality
	Benra 30 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/207 (0%)		0/203 (0%)
Serious Adverse Events
	Benra 30 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/207 (12.1%)		19/203 (9.4%)
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia	1/207 (0.5%)	1	0/203 (0%)	0
Haemolytic uraemic syndrome	1/207 (0.5%)	1	0/203 (0%)	0
Lymphadenopathy	0/207 (0%)	0	1/203 (0.5%)	1
Cardiac disorders
Acute myocardial infarction	1/207 (0.5%)	1	0/203 (0%)	0
Arrhythmia	0/207 (0%)	0	1/203 (0.5%)	1
Pericarditis	2/207 (1%)	3	0/203 (0%)	0
Ear and labyrinth disorders
Deafness neurosensory	1/207 (0.5%)	1	0/203 (0%)	0
Eye disorders
Rhegmatogenous retinal detachment	0/207 (0%)	0	1/203 (0.5%)	1
Gastrointestinal disorders
Abdominal pain upper	1/207 (0.5%)	1	0/203 (0%)	0
Coeliac disease	1/207 (0.5%)	1	0/203 (0%)	0
Gastritis	2/207 (1%)	2	0/203 (0%)	0
Oesophageal spasm	1/207 (0.5%)	1	0/203 (0%)	0
Pancreatitis acute	1/207 (0.5%)	1	0/203 (0%)	0
Reflux gastritis	1/207 (0.5%)	1	0/203 (0%)	0
Hepatobiliary disorders
Cholecystitis acute	1/207 (0.5%)	1	0/203 (0%)	0
Infections and infestations
Appendicitis perforated	0/207 (0%)	0	1/203 (0.5%)	1
Bronchitis bacterial	1/207 (0.5%)	1	0/203 (0%)	0
Herpes simplex	1/207 (0.5%)	1	0/203 (0%)	0
Influenza	0/207 (0%)	0	1/203 (0.5%)	1
Pneumonia	0/207 (0%)	0	1/203 (0.5%)	1
Pneumonia influenzal	1/207 (0.5%)	1	0/203 (0%)	0
Pneumonia streptococcal	1/207 (0.5%)	1	0/203 (0%)	0
Sinusitis	0/207 (0%)	0	1/203 (0.5%)	1
Injury, poisoning and procedural complications
Compression fracture	0/207 (0%)	0	1/203 (0.5%)	1
Craniocerebral injury	0/207 (0%)	0	1/203 (0.5%)	1
Foot fracture	0/207 (0%)	0	1/203 (0.5%)	1
Ligament rupture	0/207 (0%)	0	1/203 (0.5%)	1
Thoracic vertebral fracture	0/207 (0%)	0	1/203 (0.5%)	1
Metabolism and nutrition disorders
Type 2 diabetes mellitus	0/207 (0%)	0	1/203 (0.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/207 (0.5%)	1	0/203 (0%)	0
Osteoarthritis	1/207 (0.5%)	1	0/203 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of appendix	1/207 (0.5%)	1	0/203 (0%)	0
Lymphoma	0/207 (0%)	0	1/203 (0.5%)	1
Mucoepidermoid carcinoma of salivary gland	1/207 (0.5%)	1	0/203 (0%)	0
Uterine leiomyoma	0/207 (0%)	0	1/203 (0.5%)	1
Nervous system disorders
Cerebrospinal fistula	1/207 (0.5%)	1	0/203 (0%)	0
Ischaemic stroke	1/207 (0.5%)	1	0/203 (0%)	0
Seizure	1/207 (0.5%)	1	0/203 (0%)	0
Psychiatric disorders
Bipolar I disorder	1/207 (0.5%)	1	0/203 (0%)	0
Depression	0/207 (0%)	0	1/203 (0.5%)	1
Suicide attempt	0/207 (0%)	0	1/203 (0.5%)	1
Renal and urinary disorders
Hydronephrosis	1/207 (0.5%)	1	0/203 (0%)	0
Reproductive system and breast disorders
Prostatitis	1/207 (0.5%)	1	0/203 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	1/207 (0.5%)	1	1/203 (0.5%)	1
Epistaxis	1/207 (0.5%)	1	0/203 (0%)	0
Laryngeal leukoplakia	0/207 (0%)	0	1/203 (0.5%)	1
Skin and subcutaneous tissue disorders
Dermatitis contact	0/207 (0%)	0	1/203 (0.5%)	1
Vascular disorders
Deep vein thrombosis	0/207 (0%)	0	1/203 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Benra 30 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/207 (30.9%)		83/203 (40.9%)
Infections and infestations
Nasopharyngitis	37/207 (17.9%)	57	43/203 (21.2%)	54
Viral upper respiratory tract infection	7/207 (3.4%)	9	14/203 (6.9%)	15
Nervous system disorders
Headache	7/207 (3.4%)	9	16/203 (7.9%)	18
Respiratory, thoracic and mediastinal disorders
Asthma	21/207 (10.1%)	30	30/203 (14.8%)	54

Limitations/Caveats

During COVID-19 pandemic, for ongoing patients, patient dosing, scheduled visits, and nasal endoscopies are inevitable impacted. Week 40 was made as the primary timepoint to mitigate the impact of COVID disruptions on the primary endpoint.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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