A study to investigate the use of benralizumab in patients with Chronic Spontaneous Urticaria Who are Symptomatic Despite the Use of Antihistamines (ARROYO) - ARROYO

Study identifier:D3259C00001

ClinicalTrials.gov identifier:NCT04612725

EudraCT identifier:2020-000169-17

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase 2b Multinational, Randomised, Double-blind, Parallel- group, 24-week Placebo-controlled Study with 28-week Extension to Investigate the Use of Benralizumab in Patients with Chronic Spontaneous Urticaria Who are Symptomatic Despite the Use of Antihistamines (ARROYO)

Medical condition

Chronic Spontaneous Urticaria

Phase

Phase 2

Healthy volunteers

Study drug

Sex

All

Actual Enrollment

159

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 27 Oct 2020

Primary Completion Date: 13 Oct 2022

Study Completion Date: 28 Mar 2023

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

IQVIA

Inclusion and exclusion criteria

Inclusion Criteria

Informed Consent/Age/Gender
1. Provision of the signed and dated written informed consent of the participant prior to any mandatory study-specific procedures, sampling, and analyses.
2. Adult participants≥18 years of age at the time of signing the Informed Consent Form (ICF).
Type of Participants and Disease
3. Physician-confirmed diagnosis of CSU (also known as chronic idiopathic urticaria) for at least 6 months prior to screening (Visit 1).
4. Presence of pruritus and wheals for at least 6 consecutive weeks prior to screening (Visit 1), despite receiving standard of care, which may include second generation H1 antihistamines (at approved or up to 4-times approved doses) as monotherapy or in combination with LTRAs and/or H2 blockers.
5. Symptomatic during run-in, defined by the following:
(a) UAS7 total score of ≥ 16 with an ISS7 of ≥ 8, during the 7 days prior to randomisation (Visit 2)
(b) In-clinic UAS total score of ≥ 4 on at least one of the screening days.
6. Willing to use a second-generation H1 antihistamine at the approved dose and as monotherapy from the screening visit (Visit 1) until the end of the study.
7. Participants must complete daily PRO assessments and meet the following compliance criteria:
(a) Complete at least 80% of daily PRO assessments between Visit 1 and Visit 2 and
(b) Complete at least 6 of 7 daily PRO assessments in the 7 days prior to Visit 2.
8. Compliance with the locally-approved dose of antihistamine, maintained at randomisation.
Reproduction
9. Females of childbearing potential (FOCBP) must agree to use a highly effective method of birth control (confirmed by the Investigator) from randomisation, throughout the study duration, and within12 weeks after last dose of IP and have a negative serum pregnancy test result on Visit 1. Highly effective methods of birth control include:
(a) Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal.
(b) Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable.
(c) Intrauterine device.
(d) Intrauterine hormone-releasing system.
(e) Bilateral tubal occlusion or ligation.
(f) Sexual abstinence, ie, refraining from heterosexual intercourse (the reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant).
(g) Vasectomised sexual partner (provided that partner is the sole sexual partner of the FOCBP study participant and that the vasectomised partner has received medical assessment of the surgical success).
10. Females not of childbearing potential are defined as Females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Females will be considered postmenopausal if they have been amenorrhoeic for≥12 months prior to the planned date of randomisation without an alternative medical cause. The following age-specific requirements apply:
(a) Females<50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle-stimulating hormone (FSH) levels in the postmenopausal range. Until FSH is documented to be within menopausal range, the participant should be treated as a FOCBP.
(b) Females≥50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria

Medical Conditions
1. Participants with predominant inducible urticaria, ie, urticaria that is predominantly due to a clearly defined stimulus (eg, pressure [dermographism], delayed pressure, cold, heat, sunlight, vibration, water, physical exercise, or increased body temperature [cholinergic]).
2. Participants with diseases, other than chronic urticaria, with urticaria or angioedema symptoms such as urticaria vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1-inhibitor deficiency). Additionally, any other skin disease associated with chronic itching and/or skin lesions that, in the investigators opinion, might influence the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.).
3. Current malignancy, or history of malignancy, with the exception of: (a) Participants who have had basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided that the participant is in remission and curative therapy was completed at least 12 months prior to the date informed consent, was obtained. (b) Participants who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to the date informed consent, was obtained.
4. 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 and could: (a) Affect the safety of the participant throughout the study (b) Influence the findings of the studies or their interpretations (c) Impede the participant’s ability to complete the entire duration of study.
5. History of anaphylaxis to any biologic therapy or vaccine.
6. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with,or has failed to respond to standard of care therapy.
7. Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period which, in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant’s ability to complete entire duration of the study.
8. Current active liver disease:
(a) Chronic stable hepatitis B andC (including positive testing for hepatitis B surface antigen [HBsAg] or hepatitis C antibody), or other stable chronic liver disease are acceptable if participant otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis.
(b) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level≥3 times the upper limit of normal (ULN), confirmed by repeated testing during the run-in period. Transient increase of AST/ALT level that resolves by the time of randomisationis acceptable if in the Investigator’s opinion the participant does not have an active liver disease and meets other eligibility criteria.
9. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test. Prior/concomitant Therapy
10. Use of immunosuppressive medication, including, but not limited to: methotrexate, cyclosporine, azathioprine, topical and systemic corticosteroids within 4 weeks or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
11. Known history of allergy or reaction to any component of the IP formulation
Other
12. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
13. Receipt of any marketed (eg, omalizumab) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
14. Receipt of live attenuated vaccines 30 days prior to the date of randomisation
15. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
16. Previously received benralizumab (MEDI-563, FASENRA)
17. Change to allergen immunotherapy or new allergen immunotherapy within 30 days prior to the date of informed consent and anticipated changes in immunotherapy throughout the study
18. Planned elective major surgical procedures during the conduct of the study
19. Previous randomization in the present study
20. Concurrent enrollment in another clinical trial
21. AstraZeneca staff involved in the planning and/or conduct of the study
22. For Females only: Currently pregnant, breastfeeding, or lactating Females (a) A serum pregnancy test will be done for FOCBP at Visit 1 and a urine pregnancy test must be performed for FOCBP at each treatment visit prior to IP administration. A positive urine test result must be confirmed with a serum pregnancy test. If serum test is positive, the participant should be excluded.

Location

Research Site

Cincinnati, OH, United States, 45236

Location

Research Site

Cincinnati, OH, United States, 45229

Location

Research Site

Tampa, FL, United States, 33606

Location

Research Site

Los Angeles, CA, United States, 90025

Location

Research Site

Scottsdale, AZ, United States, 85260

Location

Research Site

Austin, TX, United States, 78745

Location

Research Site

Mission Viejo, CA, United States, 92691

Location

Research Site

Berlin, Germany, 10117

Arms	Assigned Interventions
Experimental: Benralizumab Arm 1 Benralizumab Dose A regimen A until Week 12, Dose B regimen A until Week 24, and Dose B regimen B during the extension period until Week 52 (n=30)	Biological/Vaccine: Benralizumab 2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period. Other Name: Benralizumab, Benra, Fasenra
Experimental: Benralizumab Arm 2 Benralizumab Dose A regimen A until Week 12, Dose B regimen A until Week 24,and Dose B regimen A during the extension period until Week 52 (n=30)	Biological/Vaccine: Benralizumab 2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period. Other Name: Benralizumab, Benra, Fasenra
Experimental: Benralizumab Arm 3 Benralizumab Dose B regimen A until Week 12, Dose B regimen A until Week 24, and Dose B regimen B during the extension period until Week 52 (n=30)	Biological/Vaccine: Benralizumab 2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period. Other Name: Benralizumab, Benra, Fasenra
Experimental: Benralizumab Arm 4 Benralizumab Dose B regimen A until Week 12, Dose B regimen A until Week 24, and Dose B regimen A during the extension period until Week 52 (n=30)	Biological/Vaccine: Benralizumab 2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period. Other Name: Benralizumab, Benra, Fasenra
Experimental: Placebo and Benralizumab Placebo regimen A until Week 24, benralizumab Dose B regiment A until Week 36, and Dose B regimen B until Week 52 (n=40).	Biological/Vaccine: Placebo and Benralizumab 2 induction doses of benralizumab (dose A and B) compared to placebo, and a comparison of maintenance dosing regimens (B vs A) in the 28-week extension period. Other Name: Benralizumab, Benra, Fasenra

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This Phase 2b, randomized, double-blind study was conducted in participants with chronic spontaneous urticaria (CSU) who were symptomatic despite the use of antihistamines at 46 study centers in Bulgaria, Germany, Japan, Korea, Poland, Spain, and United States of America between 27 October 2020 and 28 March 2023. The study was terminated early by the sponsor as primary results did not support the continued development of benralizumab for the indication of CSU.

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

This Phase 2b, randomized, double-blind study was conducted in participants with chronic spontaneous urticaria (CSU) who were symptomatic despite the use of antihistamines at 46 study centers in Bulgaria, Germany, Japan, Korea, Poland, Spain, and United States of America between 27 October 2020 and 28 March 2023. The study was terminated early by the sponsor as primary results did not support the continued development of benralizumab for the indication of CSU.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study had a run-in period (10 days to 4 weeks), followed by a double-blind treatment period (24 weeks) and extension period (28 weeks). A total of 155 participants were randomized and treated in this study.

Reporting Groups

	Description
Double-blind then extension period: Benralizumab 30 mg Q4W	Participants were randomized to receive benralizumab 30 milligram (mg) subcutaneous (SC) injection every 4 weeks (Q4W) until Week 24 in the double-blind treatment period and then 30 mg Q4W during the extension period until Week 52.
Double-blind then extension period: Benralizumab 30 mg Q8W	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg every 8 weeks (Q8W) during the extension period until Week 52.
Double-blind then extension period: Benralizumab 60 mg Q4W	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W during the extension period until Week 52.
Double-blind then extension period: Benralizumab 60 mg Q8W	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q8W during the extension period until Week 52.
Double-blind then extension period: Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Participant Flow: Overall Study

	Double-blind then extension period: Benralizumab 30 mg Q4W	Double-blind then extension period: Benralizumab 30 mg Q8W	Double-blind then extension period: Benralizumab 60 mg Q4W	Double-blind then extension period: Benralizumab 60 mg Q8W	Double-blind then extension period: Placebo
STARTED	30	29	28	28	40
Completed the treatment period	26	27	25	28	37
Entered extension period	24	26	25	28	37
COMPLETED	16	21	20	23	24
NOT COMPLETED	14	8	8	5	16
Adverse Event	1	3	1	0	1
Lost to Follow-up	0	1	0	0	0
Physician Decision	2	0	0	0	0
Study terminated by sponsor	3	1	2	4	5
Withdrawal by Subject	8	3	5	1	9
Unspecified	0	0	0	0	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

The full analysis set (FAS) included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Baseline Measures

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo	Total
Number of Participants [units: Participants]	59	56	40	155
Age, Customized [units: participants]
<35 years	11	15	8	34
>=35 to <=55 years	32	25	22	79
>55 years	16	16	10	42
Sex: Female, Male [units: participants]
Female	44	45	25	114
Male	15	11	15	41
Race/Ethnicity, Customized [units: participants]
White	46	42	30	118
Asian	12	12	8	32
Black or African American	1	2	0	3
Not reported	0	0	2	2
Race/Ethnicity, Customized [units: participants]
Hispanic or Latino	2	4	4	10
Not Hispanic or Latino	57	52	36	145

Outcome Measures

1. Primary Outcome Measure: Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 [ Time Frame: Baseline (Day -1) and Week 12 ]

Measure Type	Primary
Measure Name	Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12
Measure Description	The urticaria participant daily diary (UPDD) was completed twice daily (morning and evening) to capture key measures of urticaria disease activity including the itch severity score (ISS). The ISS represents severity on a scale ranging from 0 to 3 (where 0= none, 1= mild, 2= moderate and 3= severe). The ISS7 is the sum of ISS for the previous 7 days. The ISS7 represents itch severity on a scale ranging from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of itch. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time Frame	Baseline (Day -1) and Week 12
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	55	52	37
Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 [units: units on a scale] Least Squares Mean (95% Confidence Interval)	-7.50 (-8.94 to -6.05)	-8.28 (-9.76 to -6.80)	-6.49 (-8.24 to -4.74)

Statistical Analysis 1 for Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.3824
Other^[5]	-1.01
95% Confidence Interval	( -3.28 to 1.26 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in ISS7 at Week 12= Treatment + baseline ISS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.1244
Other^[5]	-1.79
95% Confidence Interval	( -4.09 to 0.50 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in ISS7 at Week 12= Treatment + baseline ISS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

2. Secondary Outcome Measure: LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 [ Time Frame: Baseline (Day -1) and Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24
Measure Description	The UPDD was completed twice daily (morning and evening) to capture key measures of urticaria disease activity including the UAS7. Participants were asked to document the number of hives they experienced on a scale ranging from 0 to 3 (where 0= none, 1= mild [1 – 6 hives/12 hour], 2= moderate [7 – 12 hives/12 hour] and 3= intense [(> 12 hives/12 hour]). The UAS7 is the sum of UAS for the previous 7 days, that is, the sum of ISS7 and HSS7. The UAS7 represents urticaria severity on a scale from 0 (minimum) to 42 (maximum). Higher scores indicate greater severity of urticaria symptoms. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time Frame	Baseline (Day -1) and Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study. Participants with data at baseline and each time point were analyzed. The overall number analyzed included those with data at baseline and at least 1 of the reported time points.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	55	53	37
LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 [units: units on a scale] Least Squares Mean (95% Confidence Interval)
Week 12	-14.48 (-17.58 to -11.38)	-16.77 (-19.94 to -13.59)	-12.41 (-16.17 to -8.65)
Week 24	-17.99 (-21.29 to -14.68)	-19.17 (-22.51 to -15.83)	-15.43 (-19.43 to -11.44)

Statistical Analysis 1 for LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.4016
Other^[5]	-2.07
95% Confidence Interval	( -6.95 to 2.80 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UAS7 at Week 12= Treatment + baseline UAS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.0819
Other^[5]	-4.36
95% Confidence Interval	( -9.28 to 0.56 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UAS7 at Week 12= Treatment + baseline UAS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.3314
Other^[5]	-2.56
95% Confidence Interval	( -7.74 to 2.63 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UAS7 at Week 24= Treatment + baseline UAS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.1582
Other^[5]	-3.74
95% Confidence Interval	( -8.95 to 1.47 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UAS7 at Week 24= Treatment + baseline UAS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: LS Mean Change From Baseline in ISS7 at Week 24 [ Time Frame: Baseline (Day -1) and Week 24 ]

Measure Type	Secondary
Measure Name	LS Mean Change From Baseline in ISS7 at Week 24
Measure Description	The UPDD was completed twice daily (morning and evening) to capture key measures of urticaria disease activity including the ISS. The ISS represents severity on a scale ranging from 0 to 3 (where 0= none, 1= mild, 2= moderate and 3= severe). The ISS7 is the sum of ISS for the previous 7 days. The ISS7 represents itch severity on a scale ranging from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of itch. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time Frame	Baseline (Day -1) and Week 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	52	53	36
LS Mean Change From Baseline in ISS7 at Week 24 [units: units on a scale] Least Squares Mean (95% Confidence Interval)	-9.19 (-10.77 to -7.61)	-9.33 (-10.93 to -7.73)	-7.57 (-9.48 to -5.66)

Statistical Analysis 1 for LS Mean Change From Baseline in ISS7 at Week 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.1995
Other^[5]	-1.62
95% Confidence Interval	( -4.10 to 0.86 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in ISS7 at Week 24= Treatment + baseline ISS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for LS Mean Change From Baseline in ISS7 at Week 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.1654
Other^[5]	-1.76
95% Confidence Interval	( -4.25 to 0.73 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in ISS7 at Week 24= Treatment + baseline ISS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Percentage of Responders at Weeks 12 and 24 [ Time Frame: Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	Percentage of Responders at Weeks 12 and 24
Measure Description	Responder was defined as a participant whose condition was considered clinically well controlled with UAS7 <=6 at specific time points. The UAS7 is the sum of UAS for the previous 7 days, that is, the sum of ISS7 and HSS7. The UAS7 represents urticaria severity on a scale from 0 (minimum) to 42 (maximum). Higher scores indicate greater severity of urticaria symptoms.
Time Frame	Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	59	56	40
Percentage of Responders at Weeks 12 and 24 [units: percentage of participants]
Week 12	22.0	21.4	10.0
Week 24	28.8	37.5	27.5

Statistical Analysis 1 for Percentage of Responders at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.1373
Other^[5]	11.72
95% Confidence Interval	( -2.37 to 25.82 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 12: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Percentage of Responders at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.1697
Other^[5]	10.73
95% Confidence Interval	( -3.42 to 24.88 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 12: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Percentage of Responders at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.9105
Other^[5]	1.03
95% Confidence Interval	( -16.90 to 18.96 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Percentage of Responders at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.3389
Other^[5]	9.27
95% Confidence Interval	( -9.37 to 27.90 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 [ Time Frame: Baseline (Day -1) and Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24
Measure Description	The UPDD was completed twice daily (morning and evening) to capture key measures of urticaria disease activity including the HSS7. Participants were asked to document the number of hives they experienced on a scale ranging from 0 to 3 (where 0= none, 1= mild [1 – 6 hives/12 hour], 2= moderate [7 – 12 hives/12 hour] and 3= intense [(> 12 hives/12 hour]). The HSS7 is the sum of hives severity score for the previous 7 days. The HSS7 represents hives severity on a scale from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of hives. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time Frame	Baseline (Day -1) and Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	55	53	37
LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 [units: units on a scale] Least Squares Mean (95% Confidence Interval)
Week 12	-7.03 (-8.84 to -5.22)	-8.47 (-10.32 to -6.62)	-5.87 (-8.06 to -3.68)
Week 24	-8.88 (-10.76 to -7.00)	-9.81 (-11.71 to -7.91)	-7.82 (-10.09 to -5.54)

Statistical Analysis 1 for LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.4203
Other^[5]	-1.16
95% Confidence Interval	( -4.00 to 1.68 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in HSS7 at Week 12= Treatment + baseline HSS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.0754
Other^[5]	-2.60
95% Confidence Interval	( -5.46 to 0.27 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in HSS7 at Week 12= Treatment + baseline HSS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.4772
Other^[5]	-1.06
95% Confidence Interval	( -4.01 to 1.89 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in HSS7 at Week 24= Treatment + baseline HSS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.1851
Other^[5]	-2.00
95% Confidence Interval	( -4.96 to 0.97 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in HSS7 at Week 24= Treatment + baseline HSS7 + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Time to >=5-Point Decrease in ISS7 [ Time Frame: From Baseline (Day -1) up to Week 24 ]

Measure Type	Secondary
Measure Name	Time to >=5-Point Decrease in ISS7
Measure Description	The time to >=5-point decrease (clinically relevant decrease) in ISS7 was reported. The ISS7 is the sum of ISS for the previous 7 days. The ISS7 represents itch severity on a scale ranging from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of itch.
Time Frame	From Baseline (Day -1) up to Week 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study. Only participants with at least 1 >=5-point decrease in ISS7 are analyzed.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	48	50	33
Time to >=5-Point Decrease in ISS7 [units: weeks] Median (95% Confidence Interval)	3.0 (2.0 to 5.0)	2.0 (2.0 to 3.0)	8.0 (3.0 to 11.0)

No statistical analysis provided for Time to >=5-Point Decrease in ISS7

7. Secondary Outcome Measure: Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 [ Time Frame: Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24
Measure Description	Complete response was defined as participants with UAS7= 0 at specific time points. The UAS7 is the sum of UAS for the previous 7 days, that is, the sum of ISS7 and HSS7. The UAS7 represents urticaria severity on a scale from 0 (minimum) to 42 (maximum). Higher scores indicate greater severity of urticaria symptoms.
Time Frame	Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	59	56	40
Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 [units: percentage of participants]
Week 12	11.9	7.1	10.0
Week 24	16.9	21.4	20.0

Statistical Analysis 1 for Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.9678

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 12: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.

Statistical Analysis 2 for Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.3689

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 12: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.

Statistical Analysis 3 for Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.6624
Other^[5]	-3.43
95% Confidence Interval	( -18.96 to 12.11 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Regression, Logistic
P-Value^[4]	0.9726
Other^[5]	0.28
95% Confidence Interval	( -15.84 to 16.40 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Week 24: Estimates included treatment group, region (Europe, North America, Asia) and baseline UAS7.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 [ Time Frame: Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24
Measure Description	The UPDD included a daily yes/no question asking whether the participant experienced angioedema during the past 24 hours. If yes, the participant was asked a follow-up question about how they treated the swelling. The percentage of angioedema-free days was calculated over the past 7 days by (number of angioedema-free days/number of non-missing responses) x 100.
Time Frame	Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study. Only participants with angioedema at baseline or history of angioedema are analyzed.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	36	28	22
Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 [units: percentage of days] Mean (Standard Deviation)
Week 12	77.50 (35.990)	85.63 (32.435)	81.93 (34.548)
Week 24	78.50 (36.992)	91.33 (27.032)	86.79 (31.798)

No statistical analysis provided for Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24

9. Secondary Outcome Measure: LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 [ Time Frame: Baseline (Day -1) and Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24
Measure Description	Urticaria disease control was assessed by the UCT using the electronic participant-reported outcome device. The UCT has a retrospective approach using a recall period of 4 weeks and responses on 5-point Likert scales with score ranging from 0 to 4 for each question. Subsequently, the scores for all 4 questions were summed up. The UCT scale range from 0 (minimum) to 16 (maximum). Higher scores indicate better disease control.
Time Frame	Baseline (Day -1) and Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	55	52	38
LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 [units: units on a scale] Least Squares Mean (95% Confidence Interval)
Week 12	4.74 (3.71 to 5.76)	6.11 (5.05 to 7.17)	5.02 (3.78 to 6.26)
Week 24	5.24 (4.04 to 6.45)	6.87 (5.65 to 8.09)	5.88 (4.44 to 7.32)

Statistical Analysis 1 for LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.7256
Other^[5]	-0.29
95% Confidence Interval	( -1.90 to 1.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UCT at Week 12= Treatment + baseline UCT + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.1890
Other^[5]	1.09
95% Confidence Interval	( -0.54 to 2.72 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UCT at Week 12= Treatment + baseline UCT + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.5048
Other^[5]	-0.63
95% Confidence Interval	( -2.51 to 1.24 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UCT at Week 24= Treatment + baseline UCT + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.2991
Other^[5]	0.99
95% Confidence Interval	( -0.89 to 2.88 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in UCT at Week 24= Treatment + baseline UCT + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

10. Secondary Outcome Measure: LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 [ Time Frame: Baseline (Day -1) and Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24
Measure Description	The CU-Q2oL is a 23-item assessment of CSU-specific health-related quality of life. Participants were asked to rate their CSU symptoms and the impact of their symptoms over the last 2 weeks on several domains: pruritus, swelling, impact on life activities, sleep problems, limits, and looks. The questions were scored as 1= not at all, 2= a little, 3= moderately, 4= very much, 5= extremely. The scores were transformed into percentages of the maximum possible score. The CU-Q2oL scale range from 0 (minimum) to 100 (maximum). Higher scores indicate greater impact of urticaria on health-related quality of life.
Time Frame	Baseline (Day -1) and Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	55	52	38
LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 [units: units on a scale] Least Squares Mean (95% Confidence Interval)
Week 12	-16.47 (-20.10 to -12.84)	-20.34 (-24.09 to -16.60)	-18.10 (-22.46 to -13.74)
Week 24	-17.60 (-21.81 to -13.40)	-22.11 (-26.38 to -17.84)	-19.07 (-24.09 to -14.05)

Statistical Analysis 1 for LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.5704
Other^[5]	1.63
95% Confidence Interval	( -4.05 to 7.32 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in CU-Q2oL at Week 12= Treatment + baseline CU-Q2oL + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.4416
Other^[5]	-2.24
95% Confidence Interval	( -7.98 to 3.50 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in CU-Q2oL at Week 12= Treatment + baseline CU-Q2oL + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.6591
Other^[5]	1.47
95% Confidence Interval	( -5.09 to 8.02 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in CU-Q2oL at Week 24= Treatment + baseline CU-Q2oL + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.3624
Other^[5]	-3.04
95% Confidence Interval	( -9.62 to 3.54 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in CU-Q2oL at Week 24= Treatment + baseline CU-Q2oL + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

11. Secondary Outcome Measure: LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 [ Time Frame: Baseline (Day -1) and Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24
Measure Description	The DLQI is a 10-item assessment of dermatology-specific health-related quality of life. Participants were asked to rate their symptoms and the impact of their symptoms over the last week on several domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The questions (except question 7) were scored on a 4-point Likert scale: 0= not at all, 1= a little, 2= a lot, 3= very much. Scoring question 7, the first part asked: 'Over the last week, has your skin prevented you from working or studying?' Scoring was for response of 0= not relevant and 3= yes. If response was 'no', a further question was asked: 'How much has your skin been a problem at work or studying', and scored as: 0= not at all, 1= a little, 2= a lot. The DLQI was calculated by summing the score of each question. The DLQI scale range from 0 (minimum) to 30 (maximum). Higher scores indicate greater impact on participant’s life.
Time Frame	Baseline (Day -1) and Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The FAS included all randomized participants who received at least 1 dose of study drug, irrespective of their protocol adherence and continued participation in the study.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	55	52	38
LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 [units: units on a scale] Least Squares Mean (95% Confidence Interval)
Week 12	-7.58 (-9.18 to -5.98)	-9.31 (-10.96 to -7.66)	-8.06 (-9.98 to -6.14)
Week 24	-8.13 (-9.84 to -6.42)	-10.25 (-11.98 to -8.51)	-9.37 (-11.41 to -7.33)

Statistical Analysis 1 for LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.7037
Other^[5]	0.48
95% Confidence Interval	( -2.02 to 2.98 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in DLQI at Week 12= Treatment + baseline DLQI + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.3320
Other^[5]	-1.25
95% Confidence Interval	( -3.78 to 1.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in DLQI at Week 12= Treatment + baseline DLQI + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24

Groups^[1]	Benralizumab 30 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.3590
Other^[5]	1.24
95% Confidence Interval	( -1.42 to 3.90 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in DLQI at Week 24= Treatment + baseline DLQI + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 4 for LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24

Groups^[1]	Benralizumab 60 mg, Placebo
Method^[3]	Other [Mixed-effect model for repeated measures]
P-Value^[4]	0.5175
Other^[5]	-0.88
95% Confidence Interval	( -3.56 to 1.80 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Change from baseline in DLQI at Week 24= Treatment + baseline DLQI + region (Europe, North America, Asia) + visit + treatment by visit.
[5]	Other relevant estimation information:
	No text entered.

12. Secondary Outcome Measure: Serum Concentration of Benralizumab [ Time Frame: Pre-dose on Weeks 4, 12 and 24 ]

Measure Type	Secondary
Measure Name	Serum Concentration of Benralizumab
Measure Description	Blood samples were collected to determine the serum concentration of benralizumab.
Time Frame	Pre-dose on Weeks 4, 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Pharmacokinetic (PK) analysis set included all participants who received study drug and from whom PK blood samples were assumed not to be affected by factors such as protocol violations and who had at least 1 quantifiable serum PK observation post first dose. Placebo group samples were not analyzed at Weeks 4 and 12 as they have not received benralizumab in double-blind treatment period.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	55	54	34
Serum Concentration of Benralizumab [units: nanogram per milliliter (ng/mL)] Mean (Standard Deviation)
Week 4	990.515 (448.6799)	2167.606 (991.7509)
Week 12	1321.373 (740.5070)	3145.352 (1577.6726)
Week 24	1372.806 (883.5830)	1638.810 (946.9466)	NA (NA)^[1]

No statistical analysis provided for Serum Concentration of Benralizumab

13. Secondary Outcome Measure: Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab [ Time Frame: Pre-dose on Weeks 12 and 24 ]

Measure Type	Secondary
Measure Name	Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab
Measure Description	Blood samples were measured for the presence of ADAs for benralizumab using validated assays. The ADA incidence (treatment-emergent ADA positive) was defined as ADA negative at baseline and post-baseline ADA positive, or ADA positive at baseline and boosted the pre-existing titre by > 4-fold during the study period. Persistently positive was defined as ADA negative at baseline and positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive was defined as ADA negative at baseline, having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. The median of maximum titres was calculated based on the maximum titre for each ADA positive participant within each treatment group (including both baseline and post-baseline measurements).
Time Frame	Pre-dose on Weeks 12 and 24
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Safety analysis set included all participants who received at least 1 dose of study drug. Participants with data at baseline and at least 1 post baseline sample were analyzed.

Reporting Groups

	Description
Benralizumab 30 mg	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period and then 30 mg Q4W or Q8W during the extension period until Week 52.
Benralizumab 60 mg	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period followed by 30 mg Q4W or Q8W during the extension period until Week 52.
Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period followed by benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52.

Measured Values

	Benralizumab 30 mg	Benralizumab 60 mg	Placebo
Number of Participants Analyzed [units:participants]	59	56	40
Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab [units: participants]
ADA prevalence	18	13	4
ADA negative (both baseline and post-baseline negative)	37	41	33
Only baseline positive	1	1	0
Baseline and at least 1 post-baseline positive	3	4	0
ADA incidence	15	10	4
ADA persistently positive	10	4	4
ADA transiently positive	5	5	0
ADA positive with maximum titre > median of maximum titres	8	5	1
ADA positive with maximum titre <= median of maximum titres	10	8	3

No statistical analysis provided for Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab

Serious Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) are reported from the first dose administration up to 30days after the last dose of study drug, a maximum of approximately 57 weeks.
Additional Description	The Safety analysis set included all participants who received at least 1 dose of study drug. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.

Reporting Groups

	Description
Double-blind period: Benralizumab 30 mg Q4W	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period.
Double-blind period: Benralizumab 60 mg Q4W	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period.
Double-blind period: Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period.
Extension period: Benralizumab 30 mg Q4W	Participants were randomized to receive benralizumab 30 mg SC injection Q4W in the extension period until Week 52.
Extension period: Benralizumab 30 mg Q8W	Participants were randomized to receive benralizumab 30 mg SC injection Q8W in the extension period until Week 52.
Extension period: Placebo to Benralizumab	Participants randomized to placebo in the double-blind period received benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52 in the extension period.

Serious Adverse Events

Double-blind period: Benralizumab 30 mg Q4W

Double-blind period: Benralizumab 60 mg Q4W

Double-blind period: Placebo

Extension period: Benralizumab 30 mg Q4W

Extension period: Benralizumab 30 mg Q8W

Extension period: Placebo to Benralizumab

Total, serious adverse events

# participants affected / at risk

3/59 (5.08%)

1/56 (1.79%)

0/40 (0.00%)

0/49 (0.00%)

3/54 (5.56%)

1/37 (2.70%)

Renal and urinary disorders

Ureterolithiasis¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

0/40 (0.00%)

0/49 (0.00%)

1/54 (1.85%)

0/37 (0.00%)

# events

Hepatobiliary disorders

Biliary colic¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

0/40 (0.00%)

0/49 (0.00%)

0/54 (0.00%)

0/37 (0.00%)

# events

Immune system disorders

Hypersensitivity¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

0/40 (0.00%)

0/49 (0.00%)

0/54 (0.00%)

0/37 (0.00%)

# events

Nervous system disorders

Subarachnoid haemorrhage¹,^†

# participants affected / at risk

1/59 (1.69%)

0/56 (0.00%)

0/40 (0.00%)

0/49 (0.00%)

0/54 (0.00%)

0/37 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Asthma¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

0/40 (0.00%)

0/49 (0.00%)

0/54 (0.00%)

1/37 (2.70%)

# events

Skin and subcutaneous tissue disorders

Urticaria¹,^†

# participants affected / at risk

0/59 (0.00%)

1/56 (1.79%)

0/40 (0.00%)

0/49 (0.00%)

0/54 (0.00%)

0/37 (0.00%)

# events

Injury, poisoning and procedural complications

Meniscus injury¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

0/40 (0.00%)

0/49 (0.00%)

1/54 (1.85%)

0/37 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Bladder cancer¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

0/40 (0.00%)

0/49 (0.00%)

1/54 (1.85%)

0/37 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 25.0

Other Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) are reported from the first dose administration up to 30days after the last dose of study drug, a maximum of approximately 57 weeks.
Additional Description	The Safety analysis set included all participants who received at least 1 dose of study drug. Only TEAEs that started or worsened in severity on or after first dose of study drug are reported. TEAEs occurred prior to first dose of study drug are not reported as it was pre-specified to report only TEAEs that started or worsened in severity on or after first dose of study drug.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Double-blind period: Benralizumab 30 mg Q4W	Participants were randomized to receive benralizumab 30 mg SC injection Q4W until Week 24 in the double-blind treatment period.
Double-blind period: Benralizumab 60 mg Q4W	Participants were randomized to receive benralizumab 60 mg SC injection Q4W until Week 12 and then 30 mg Q4W until Week 24 in the double-blind treatment period.
Double-blind period: Placebo	Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period.
Extension period: Benralizumab 30 mg Q4W	Participants were randomized to receive benralizumab 30 mg SC injection Q4W in the extension period until Week 52.
Extension period: Benralizumab 30 mg Q8W	Participants were randomized to receive benralizumab 30 mg SC injection Q8W in the extension period until Week 52.
Extension period: Placebo to Benralizumab	Participants randomized to placebo in the double-blind period received benralizumab 30 mg SC injection Q4W until Week 36 and then 30 mg Q8W until Week 52 in the extension period.

Other Adverse Events

Double-blind period: Benralizumab 30 mg Q4W

Double-blind period: Benralizumab 60 mg Q4W

Double-blind period: Placebo

Extension period: Benralizumab 30 mg Q4W

Extension period: Benralizumab 30 mg Q8W

Extension period: Placebo to Benralizumab

Total, other (not including serious) adverse events

# participants affected / at risk

14/59 (23.73%)

13/56 (23.21%)

10/40 (25.00%)

16/49 (32.65%)

12/54 (22.22%)

11/37 (29.73%)

Infections and infestations

COVID-19¹,^†

# participants affected / at risk

5/59 (8.47%)

5/56 (8.93%)

1/40 (2.50%)

4/49 (8.16%)

4/54 (7.41%)

5/37 (13.51%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

1/59 (1.69%)

4/56 (7.14%)

2/40 (5.00%)

5/49 (10.20%)

2/54 (3.70%)

2/37 (5.41%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/59 (5.08%)

3/56 (5.36%)

2/40 (5.00%)

2/49 (4.08%)

1/54 (1.85%)

1/37 (2.70%)

# events

Infections and infestations

Sinusitis¹,^†

# participants affected / at risk

2/59 (3.39%)

0/56 (0.00%)

1/40 (2.50%)

1/49 (2.04%)

0/54 (0.00%)

3/37 (8.11%)

# events

Injury, poisoning and procedural complications

Ligament sprain¹,^†

# participants affected / at risk

0/59 (0.00%)

0/56 (0.00%)

1/40 (2.50%)

3/49 (6.12%)

1/54 (1.85%)

0/37 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

2/59 (3.39%)

0/56 (0.00%)

2/40 (5.00%)

0/49 (0.00%)

1/54 (1.85%)

3/37 (8.11%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/59 (0.00%)

2/56 (3.57%)

1/40 (2.50%)

2/49 (4.08%)

3/54 (5.56%)

0/37 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

3/59 (5.08%)

1/56 (1.79%)

1/40 (2.50%)

1/49 (2.04%)

0/54 (0.00%)

0/37 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 25.0

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study was terminated early by the sponsor as the primary analysis results did not support the continued development of benralizumab for the indication of CSU.

Results Point of Contact

Name/Title:	Global Clinical Lead
Organization:	AstraZeneca
Phone	1-877-240-9479
E-mail:	[email protected]

Documents available

ARROYO Patient Brochure
Download
ARROYO Patient Flyer
Download
Redacted CSR synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Sabine Altrichter

Charite Universitaetsmedizin Berlin - Campus Charite Mitte

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

ARROYO Patient Brochure

ARROYO Patient Flyer

Redacted CSR synopsis

Trial Results Summaries