Chronic Spontaneous Urticaria
Conditions
Keywords
chronic spontaneous urticaria,, skin lesion,, pruritus and wheals
Brief summary
The purpose of this study is to investigate the use of benralizumab is effective in the treatment of chronic spontaneous urticaria (CSU) who are symptomatic despite the use of antihistamines.
Detailed description
The aim of this study is to investigate the use of benralizumab as treatment for patients with chronic spontaneous urticaria (CSU) who are symptomatic despite the use of antihistamines. It is proposed that benralizumab will deplete eosinophils and basophils from affected skin, improve symptoms of CSU, and improve CSU-related quality of life. This Phase 2b study is designed to evaluate induction and maintenance dosing regimens.
Interventions
BIOLOGICALBenralizumab
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.
BIOLOGICALPlacebo 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.
Sponsors
Iqvia Pty Ltd
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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: 1. UAS7 total score of ≥ 16 with an ISS7 of ≥ 8, during the 7 days prior to randomisation (Visit 2) 2. 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: 1. Complete at least 80% of daily PRO assessments between Visit 1 and Visit 2 and 2. 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: 1. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal. 2. Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable. 3. Intrauterine device. 4. Intrauterine hormone-releasing system. 5. Bilateral tubal occlusion or ligation. 6. 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). 7. 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: 1. 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. 2. 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: 1. 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. 2. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 | Baseline (Day -1) and Week 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LS Mean Change From Baseline in ISS7 at Week 24 | Baseline (Day -1) and Week 24 | 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. |
| Percentage of Responders at Weeks 12 and 24 | Weeks 12 and 24 | 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. |
| LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 | Baseline (Day -1) and Weeks 12 and 24 | 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 to >=5-Point Decrease in ISS7 | From Baseline (Day -1) up to Week 24 | 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. |
| Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 | Weeks 12 and 24 | 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. |
| LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 | Baseline (Day -1) and Weeks 12 and 24 | 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. |
| LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 | Baseline (Day -1) and Weeks 12 and 24 | 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. |
| LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 | Baseline (Day -1) and Weeks 12 and 24 | 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. |
| LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 | Baseline (Day -1) and Weeks 12 and 24 | 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. |
| Serum Concentration of Benralizumab | Pre-dose on Weeks 4, 12 and 24 | Blood samples were collected to determine the serum concentration of benralizumab. |
| Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | Pre-dose on Weeks 12 and 24 | 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). |
| Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 | Weeks 12 and 24 | 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. |
Countries
Bulgaria, Germany, Japan, Poland, South Korea, Spain, United States
Participant flow
Recruitment details
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
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 59 |
| 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. | 56 |
| 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. | 40 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 3 | 1 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Physician Decision | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 3 | 1 | 2 | 4 | 5 |
| Overall Study | Withdrawal by Subject | 8 | 3 | 5 | 1 | 9 |
Baseline characteristics
| Characteristic | Benralizumab 30 mg | Benralizumab 60 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Customized >=35 to <=55 years | 32 Participants | 25 Participants | 22 Participants | 79 Participants |
| Age, Customized <35 years | 11 Participants | 15 Participants | 8 Participants | 34 Participants |
| Age, Customized >55 years | 16 Participants | 16 Participants | 10 Participants | 42 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 12 Participants | 8 Participants | 32 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 2 Participants | 4 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 57 Participants | 52 Participants | 36 Participants | 145 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 46 Participants | 42 Participants | 30 Participants | 118 Participants |
| Sex: Female, Male Female | 44 Participants | 45 Participants | 25 Participants | 114 Participants |
| Sex: Female, Male Male | 15 Participants | 11 Participants | 15 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 56 | 0 / 40 | 0 / 49 | 0 / 54 | 0 / 37 |
| other Total, other adverse events | 14 / 59 | 13 / 56 | 10 / 40 | 16 / 49 | 12 / 54 | 11 / 37 |
| serious Total, serious adverse events | 3 / 59 | 1 / 56 | 0 / 40 | 0 / 49 | 3 / 54 | 1 / 37 |
Outcome results
Primary
Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12
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
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Benralizumab 30 mg | Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 | -7.50 units on a scale |
| Benralizumab 60 mg | Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 | -8.28 units on a scale |
| Placebo | Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 | -6.49 units on a scale |
p-value: 0.382495% CI: [-3.28, 1.26]Mixed-effect model for repeated measures
p-value: 0.124495% CI: [-4.09, 0.5]Mixed-effect model for repeated measures
Secondary
LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Benralizumab 30 mg | LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 | Week 12 | -16.47 units on a scale |
| Benralizumab 30 mg | LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 | Week 24 | -17.60 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 | Week 12 | -20.34 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 | Week 24 | -22.11 units on a scale |
| Placebo | LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 | Week 12 | -18.10 units on a scale |
| Placebo | LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 | Week 24 | -19.07 units on a scale |
p-value: 0.570495% CI: [-4.05, 7.32]Mixed-effect model for repeated measures
p-value: 0.441695% CI: [-7.98, 3.5]Mixed-effect model for repeated measures
p-value: 0.659195% CI: [-5.09, 8.02]Mixed-effect model for repeated measures
p-value: 0.362495% CI: [-9.62, 3.54]Mixed-effect model for repeated measures
Secondary
LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Benralizumab 30 mg | LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 | Week 12 | -7.58 units on a scale |
| Benralizumab 30 mg | LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 | Week 24 | -8.13 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 | Week 12 | -9.31 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 | Week 24 | -10.25 units on a scale |
| Placebo | LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 | Week 12 | -8.06 units on a scale |
| Placebo | LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 | Week 24 | -9.37 units on a scale |
p-value: 0.703795% CI: [-2.02, 2.98]Mixed-effect model for repeated measures
p-value: 0.33295% CI: [-3.78, 1.29]Mixed-effect model for repeated measures
p-value: 0.35995% CI: [-1.42, 3.9]Mixed-effect model for repeated measures
p-value: 0.517595% CI: [-3.56, 1.8]Mixed-effect model for repeated measures
Secondary
LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Benralizumab 30 mg | LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 | Week 12 | -7.03 units on a scale |
| Benralizumab 30 mg | LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 | Week 24 | -8.88 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 | Week 12 | -8.47 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 | Week 24 | -9.81 units on a scale |
| Placebo | LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 | Week 12 | -5.87 units on a scale |
| Placebo | LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 | Week 24 | -7.82 units on a scale |
p-value: 0.420395% CI: [-4, 1.68]Mixed-effect model for repeated measures
p-value: 0.075495% CI: [-5.46, 0.27]Mixed-effect model for repeated measures
p-value: 0.477295% CI: [-4.01, 1.89]Mixed-effect model for repeated measures
p-value: 0.185195% CI: [-4.96, 0.97]Mixed-effect model for repeated measures
Secondary
LS Mean Change From Baseline in ISS7 at Week 24
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
Population: 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.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Benralizumab 30 mg | LS Mean Change From Baseline in ISS7 at Week 24 | -9.19 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in ISS7 at Week 24 | -9.33 units on a scale |
| Placebo | LS Mean Change From Baseline in ISS7 at Week 24 | -7.57 units on a scale |
p-value: 0.199595% CI: [-4.1, 0.86]Mixed-effect model for repeated measures
p-value: 0.165495% CI: [-4.25, 0.73]Mixed-effect model for repeated measures
Secondary
LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Benralizumab 30 mg | LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 | Week 12 | -14.48 units on a scale |
| Benralizumab 30 mg | LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 | Week 24 | -17.99 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 | Week 12 | -16.77 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 | Week 24 | -19.17 units on a scale |
| Placebo | LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 | Week 12 | -12.41 units on a scale |
| Placebo | LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 | Week 24 | -15.43 units on a scale |
p-value: 0.401695% CI: [-6.95, 2.8]Mixed-effect model for repeated measures
p-value: 0.081995% CI: [-9.28, 0.56]Mixed-effect model for repeated measures
p-value: 0.331495% CI: [-7.74, 2.63]Mixed-effect model for repeated measures
p-value: 0.158295% CI: [-8.95, 1.47]Mixed-effect model for repeated measures
Secondary
LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Benralizumab 30 mg | LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 | Week 12 | 4.74 units on a scale |
| Benralizumab 30 mg | LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 | Week 24 | 5.24 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 | Week 12 | 6.11 units on a scale |
| Benralizumab 60 mg | LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 | Week 24 | 6.87 units on a scale |
| Placebo | LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 | Week 12 | 5.02 units on a scale |
| Placebo | LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 | Week 24 | 5.88 units on a scale |
p-value: 0.725695% CI: [-1.9, 1.32]Mixed-effect model for repeated measures
p-value: 0.18995% CI: [-0.54, 2.72]Mixed-effect model for repeated measures
p-value: 0.504895% CI: [-2.51, 1.24]Mixed-effect model for repeated measures
p-value: 0.299195% CI: [-0.89, 2.88]Mixed-effect model for repeated measures
Secondary
Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30 mg | Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 | Week 24 | 78.50 percentage of days | Standard Deviation 36.992 |
| Benralizumab 30 mg | Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 | Week 12 | 77.50 percentage of days | Standard Deviation 35.99 |
| Benralizumab 60 mg | Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 | Week 12 | 85.63 percentage of days | Standard Deviation 32.435 |
| Benralizumab 60 mg | Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 | Week 24 | 91.33 percentage of days | Standard Deviation 27.032 |
| Placebo | Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 | Week 12 | 81.93 percentage of days | Standard Deviation 34.548 |
| Placebo | Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 | Week 24 | 86.79 percentage of days | Standard Deviation 31.798 |
Secondary
Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab
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
Population: 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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA positive with maximum titre <= median of maximum titres | 10 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | Baseline and at least 1 post-baseline positive | 3 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA persistently positive | 10 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA incidence | 15 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA positive with maximum titre > median of maximum titres | 8 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA negative (both baseline and post-baseline negative) | 37 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA prevalence | 18 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA transiently positive | 5 Participants |
| Benralizumab 30 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | Only baseline positive | 1 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | Baseline and at least 1 post-baseline positive | 4 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA prevalence | 13 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA negative (both baseline and post-baseline negative) | 41 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | Only baseline positive | 1 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA incidence | 10 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA persistently positive | 4 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA transiently positive | 5 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA positive with maximum titre > median of maximum titres | 5 Participants |
| Benralizumab 60 mg | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA positive with maximum titre <= median of maximum titres | 8 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA negative (both baseline and post-baseline negative) | 33 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | Only baseline positive | 0 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA transiently positive | 0 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA prevalence | 4 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA positive with maximum titre <= median of maximum titres | 3 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA incidence | 4 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | Baseline and at least 1 post-baseline positive | 0 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA positive with maximum titre > median of maximum titres | 1 Participants |
| Placebo | Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab | ADA persistently positive | 4 Participants |
Secondary
Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg | Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 | Week 12 | 11.9 percentage of participants |
| Benralizumab 30 mg | Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 | Week 24 | 16.9 percentage of participants |
| Benralizumab 60 mg | Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 | Week 12 | 7.1 percentage of participants |
| Benralizumab 60 mg | Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 | Week 24 | 21.4 percentage of participants |
| Placebo | Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 | Week 12 | 10.0 percentage of participants |
| Placebo | Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 | Week 24 | 20.0 percentage of participants |
p-value: 0.9678Regression, Logistic
p-value: 0.3689Regression, Logistic
p-value: 0.662495% CI: [-18.96, 12.11]Regression, Logistic
p-value: 0.972695% CI: [-15.84, 16.4]Regression, Logistic
Secondary
Percentage of Responders at Weeks 12 and 24
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
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benralizumab 30 mg | Percentage of Responders at Weeks 12 and 24 | Week 12 | 22.0 percentage of participants |
| Benralizumab 30 mg | Percentage of Responders at Weeks 12 and 24 | Week 24 | 28.8 percentage of participants |
| Benralizumab 60 mg | Percentage of Responders at Weeks 12 and 24 | Week 12 | 21.4 percentage of participants |
| Benralizumab 60 mg | Percentage of Responders at Weeks 12 and 24 | Week 24 | 37.5 percentage of participants |
| Placebo | Percentage of Responders at Weeks 12 and 24 | Week 24 | 27.5 percentage of participants |
| Placebo | Percentage of Responders at Weeks 12 and 24 | Week 12 | 10.0 percentage of participants |
p-value: 0.137395% CI: [-2.37, 25.82]Regression, Logistic
p-value: 0.169795% CI: [-3.42, 24.88]Regression, Logistic
p-value: 0.910595% CI: [-16.9, 18.96]Regression, Logistic
p-value: 0.338995% CI: [-9.37, 27.9]Regression, Logistic
Secondary
Serum Concentration of Benralizumab
Blood samples were collected to determine the serum concentration of benralizumab.
Time frame: Pre-dose on Weeks 4, 12 and 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benralizumab 30 mg | Serum Concentration of Benralizumab | Week 4 | 990.515 nanogram per milliliter (ng/mL) | Standard Deviation 448.6799 |
| Benralizumab 30 mg | Serum Concentration of Benralizumab | Week 24 | 1372.806 nanogram per milliliter (ng/mL) | Standard Deviation 883.583 |
| Benralizumab 30 mg | Serum Concentration of Benralizumab | Week 12 | 1321.373 nanogram per milliliter (ng/mL) | Standard Deviation 740.507 |
| Benralizumab 60 mg | Serum Concentration of Benralizumab | Week 12 | 3145.352 nanogram per milliliter (ng/mL) | Standard Deviation 1577.6726 |
| Benralizumab 60 mg | Serum Concentration of Benralizumab | Week 4 | 2167.606 nanogram per milliliter (ng/mL) | Standard Deviation 991.7509 |
| Benralizumab 60 mg | Serum Concentration of Benralizumab | Week 24 | 1638.810 nanogram per milliliter (ng/mL) | Standard Deviation 946.9466 |
| Placebo | Serum Concentration of Benralizumab | Week 24 | NA nanogram per milliliter (ng/mL) | — |
Secondary
Time to >=5-Point Decrease in ISS7
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
Population: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Benralizumab 30 mg | Time to >=5-Point Decrease in ISS7 | 3.0 weeks |
| Benralizumab 60 mg | Time to >=5-Point Decrease in ISS7 | 2.0 weeks |
| Placebo | Time to >=5-Point Decrease in ISS7 | 8.0 weeks |