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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-000169-17 | EudraCT Number |
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Study did not meet primary endpoint
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| Name | Class |
|---|---|
| IQVIA Pty Ltd | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Benralizumab Arm 1 | Experimental | 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) |
|
| Benralizumab Arm 2 | Experimental | 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) |
|
| Benralizumab Arm 3 | Experimental | 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) |
|
| Benralizumab Arm 4 | Experimental | 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) |
|
| Placebo and Benralizumab | Experimental | Placebo regimen A until Week 24, benralizumab Dose B regiment A until Week 36, and Dose B regimen B until Week 52 (n=40). |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benralizumab | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Day -1) and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Informed Consent/Age/Gender
Provision of the signed and dated written informed consent of the participant prior to any mandatory study-specific procedures, sampling, and analyses.
Adult participants≥18 years of age at the time of signing the Informed Consent Form (ICF).
Type of Participants and Disease
Physician-confirmed diagnosis of CSU (also known as chronic idiopathic urticaria) for at least 6 months prior to screening (Visit 1).
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.
Symptomatic during run-in, defined by the following:
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.
Participants must complete daily PRO assessments and meet the following compliance criteria:
Compliance with the locally-approved dose of antihistamine, maintained at randomisation.
Reproduction
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:
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:
Exclusion Criteria:
Medical Conditions
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]).
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.).
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.
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.
History of anaphylaxis to any biologic therapy or vaccine.
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.
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.
Current active liver disease:
A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test. Prior/concomitant Therapy
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.
Known history of allergy or reaction to any component of the IP formulation Other
Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
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.
Receipt of live attenuated vaccines 30 days prior to the date of randomisation
Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
Previously received benralizumab (MEDI-563, FASENRA)
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
Planned elective major surgical procedures during the conduct of the study
Previous randomization in the present study
Concurrent enrollment in another clinical trial
AstraZeneca staff involved in the planning and/or conduct of the study
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.
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| Name | Affiliation | Role |
|---|---|---|
| Sabine Altrichter, MD | Charite Universitaetsmedizin Berlin - Campus Charite Mitte | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Scottsdale | Arizona | 85260 | United States | ||
| Research Site |
Not provided
| Label | URL |
|---|---|
| ARROYO Patient Brochure | View source |
| ARROYO Patient Flyer | View source |
Not provided
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | May 31, 2021 | Oct 10, 2023 |
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|
| Placebo and Benralizumab | Biological | 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. |
|
|
| Baseline (Day -1) and Weeks 12 and 24 |
| 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. | Baseline (Day -1) and Week 24 |
| 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. | Weeks 12 and 24 |
| 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. | Baseline (Day -1) and Weeks 12 and 24 |
| 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. | From Baseline (Day -1) up to Week 24 |
| 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. | Weeks 12 and 24 |
| 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. | Weeks 12 and 24 |
| 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. | Baseline (Day -1) and Weeks 12 and 24 |
| 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. | Baseline (Day -1) and Weeks 12 and 24 |
| 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. | Baseline (Day -1) and Weeks 12 and 24 |
| Serum Concentration of Benralizumab | Blood samples were collected to determine the serum concentration of benralizumab. | Pre-dose on Weeks 4, 12 and 24 |
| 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). | Pre-dose on Weeks 12 and 24 |
| Los Angeles |
| California |
| 90025 |
| United States |
| Research Site | Mission Viejo | California | 92691 | United States |
| Research Site | Newport Beach | California | 92663 | United States |
| Research Site | Miami | Florida | 33173 | United States |
| Research Site | Tampa | Florida | 33606 | United States |
| Research Site | Columbus | Georgia | 31904 | United States |
| Research Site | Ypsilanti | Michigan | 48197 | United States |
| Research Site | Cincinnati | Ohio | 45229 | United States |
| Research Site | Cincinnati | Ohio | 45236 | United States |
| Research Site | Norman | Oklahoma | 73071 | United States |
| Research Site | Austin | Texas | 78745 | United States |
| Research Site | Haskovo | 6300 | Bulgaria |
| Research Site | Pleven | 5800 | Bulgaria |
| Research Site | Rousse | 7013 | Bulgaria |
| Research Site | Sofia | 1000 | Bulgaria |
| Research Site | Sofia | 1463 | Bulgaria |
| Research Site | Sofia | 1606 | Bulgaria |
| Research Site | Sofia | 1680 | Bulgaria |
| Research Site | Berlin | 10117 | Germany |
| Research Site | Dresden | 01307 | Germany |
| Research Site | Leipzig | 04103 | Germany |
| Research Site | Hiroshima | 734-8551 | Japan |
| Research Site | Kamimashikigun, | 861-3106 | Japan |
| Research Site | Kawasaki-shi | 211-0063 | Japan |
| Research Site | Kobe | 650-0017 | Japan |
| Research Site | Sakaishi | 593-8324 | Japan |
| Research Site | Gdansk | 80-546 | Poland |
| Research Site | Krakow | 30-033 | Poland |
| Research Site | Poznan | 60-214 | Poland |
| Research Site | Warsaw | 02-507 | Poland |
| Research Site | Wroclaw | 50-449 | Poland |
| Research Site | Seoul | 03722 | South Korea |
| Research Site | Seoul | 06973 | South Korea |
| Research Site | Seoul | 6591 | South Korea |
| Research Site | Alicante | 03010 | Spain |
| Research Site | Barcelona | 8003 | Spain |
| Research Site | Córdoba | 14004 | Spain |
| Research Site | Madrid | 28040 | Spain |
| Research Site | Manises | 46940 | Spain |
| Redacted CSR synopsis | View source |
| 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
| Completed the Treatment Period |
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| Entered Extension Period |
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| COMPLETED |
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| NOT COMPLETED |
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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.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline (Day -1) and Week 12 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline (Day -1) and Weeks 12 and 24 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline (Day -1) and Week 24 |
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| 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. | 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. | Posted | Number | percentage of participants | Weeks 12 and 24 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline (Day -1) and Weeks 12 and 24 |
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| 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. | 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. | Posted | Median | 95% Confidence Interval | weeks | From Baseline (Day -1) up to Week 24 |
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| 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. | 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. | Posted | Number | percentage of participants | Weeks 12 and 24 |
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| 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. | 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. | Posted | Mean | Standard Deviation | percentage of days | Weeks 12 and 24 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline (Day -1) and Weeks 12 and 24 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline (Day -1) and Weeks 12 and 24 |
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| 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. | 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. | Posted | Least Squares Mean | 95% Confidence Interval | units on a scale | Baseline (Day -1) and Weeks 12 and 24 |
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| Secondary | Serum Concentration of Benralizumab | Blood samples were collected to determine the serum concentration of benralizumab. | 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. | Posted | Mean | Standard Deviation | nanogram per milliliter (ng/mL) | Pre-dose on Weeks 4, 12 and 24 |
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| 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). | 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. | Posted | Count of Participants | Participants | Pre-dose on Weeks 12 and 24 |
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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.
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 59 | 3 | 59 | 14 | 59 |
| EG001 | 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. | 0 | 56 | 1 | 56 | 13 | 56 |
| EG002 | Double-blind Period: Placebo | Participants were randomized to receive placebo matching with benralizumab Q4W until Week 24 in the double-blind treatment period. | 0 | 40 | 0 | 40 | 10 | 40 |
| EG003 | Extension Period: Benralizumab 30 mg Q4W | Participants were randomized to receive benralizumab 30 mg SC injection Q4W in the extension period until Week 52. | 0 | 49 | 0 | 49 | 16 | 49 |
| EG004 | Extension Period: Benralizumab 30 mg Q8W | Participants were randomized to receive benralizumab 30 mg SC injection Q8W in the extension period until Week 52. | 0 | 54 | 3 | 54 | 12 | 54 |
| EG005 | 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. | 0 | 37 | 1 | 37 | 11 | 37 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ureterolithiasis | Renal and urinary disorders | MedDRA 25.0 | Systematic Assessment |
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| Biliary colic | Hepatobiliary disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Hypersensitivity | Immune system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Subarachnoid haemorrhage | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 25.0 | Systematic Assessment |
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| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Meniscus injury | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
| |
| Bladder cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 25.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 25.0 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 25.0 | Systematic Assessment |
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| Ligament sprain | Injury, poisoning and procedural complications | MedDRA 25.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 25.0 | Systematic Assessment |
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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.
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca | 1-877-240-9479 | information.center@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 16, 2020 | Oct 10, 2023 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D000080223 | Chronic Urticaria |
| D011537 | Pruritus |
| D014581 | Urticaria |
| ID | Term |
|---|---|
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012877 | Skin Manifestations |
| D012816 | Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C571386 | benralizumab |
Not provided
Not provided
Not provided
| >=35 to <=55 years |
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| >55 years |
|
| Male |
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| Asian |
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| Black or African American |
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| Not reported |
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| Not Hispanic or Latino |
|
| Mixed-effect model for repeated measures |
| 0.1244 |
Change from baseline in ISS7 at Week 12= Treatment + baseline ISS7 + region (Europe, North America, Asia) + visit + treatment by visit. |
| LS mean difference |
| -1.79 |
| 2-Sided |
| 95 |
| -4.09 |
| 0.50 |
| Superiority |
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. |
| OG002 | 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. |
|
|
|
| OG002 |
| 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. |
|
|
|
|
|
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| OG002 | 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. |
|
|
|
|
|
|
|
|
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. |
|
|
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. |
|
|
|
| OG002 | 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. |
|
|
|
| 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. |
| OG002 | 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. |
|
|
|
|
|
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.
| OG002 | 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. |
|
|