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A Study to Investigate the Use of Benralizumab in Patients With Chronic Spontaneous Urticaria Who Are Symptomatic Despite the Use of Antihistamines (ARROYO) (ARROYO)

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ClinicalTrials.gov Identifier: NCT04612725
Recruitment Status : Recruiting
First Posted : November 3, 2020
Last Update Posted : February 10, 2021
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Chronic Spontaneous Urticaria Biological: Benralizumab Biological: Placebo and Benralizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 2b Multinational, Randomised, Double-blind, Parallel- Group, 24-week Placebo-controlled Study With 28-week Extension to Investigate the Use of Benralizumab in Patients With Chronic Spontaneous Urticaria Who Are Symptomatic Despite the Use of Antihistamines (ARROYO)
Actual Study Start Date : October 27, 2020
Estimated Primary Completion Date : March 2, 2022
Estimated Study Completion Date : November 9, 2022

Resource links provided by the National Library of Medicine


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

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

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

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

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




Primary Outcome Measures :
  1. Change from baseline in weekly Itch Severity Score (ISS7) at Week 12 [ Time Frame: Week 12 ]
    Change from baseline in weekly Itch Severity Score (ISS7) at Week 12 between benralizumab and placebo. The minimum ISS7 is 0 and the maximum is 21, being 21 the most severe score. The baseline ISS7 will be the sum of the ISS during the 7 days prior to day of randomisation. The ISS7 at Week 12 will be the sum of the daily ISS during the previous 7 days.


Secondary Outcome Measures :
  1. Change from baseline in Urticaria Activity Score (UAS7) at Week 12 [ Time Frame: Week 12 for all patients ]
  2. Change from baseline in Urticaria Activity Score (UAS7) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ]
  3. Proportion of responders Urticaria Activity Score (UAS7≤6) at Week 12 [ Time Frame: Week 12 for all patients ]
  4. Change from baseline in weekly hives severity score (HSS7) at Week 12 [ Time Frame: Week 12 for all patients ]
    The minimum HSS7 is 0 and the maximum is 21. The baseline HSS7 will be the sum of the HSS during the 7 days prior to day of randomisation. The HSS7 at Week 12 will be the sum of the daily HSS during the previous 7 days.

  5. Time to ≥ 5 point decrease (clinically relevant decrease) in Itch Severity Score (ISS7) [ Time Frame: Week 12 for all patients ]
  6. Proportion of participants with complete Urticaria Activity Score (UAS7) response (Urticaria Activity Score =0) at Week 12 [ Time Frame: Week 12 for all patients ]
  7. Measures of angioedema activity at Week 12 in patients with angioedema at baseline [ Time Frame: Week 12 for all patients ]

    The Urticaria Patient Daily Diary includes a daily yes/no question asking whether the participant experienced angioedema during the past 24 hours. If yes, the participant is asked a follow-up question about how they treated the swelling:

    0 = Did nothing

    1. = Took some prescription or non-prescription medication,
    2. = Called my doctor, nurse or nurse practitioner,
    3. = Went to see my doctor, nurse or nurse practitioner,
    4. = Went to the emergency room at the hospital,
    5. = Was hospitalized. The percentage of angioedema free days will be calculated over the past 7 days.

  8. Change from baseline in Urticaria Control Test (UCT) at Week 12 [ Time Frame: Week 12 for all patients ]
    The minimum and maximum UCT scores are 0 and 16, with 16 points indicating complete disease control. The UCT score will be calculated when all four questions are answered, otherwise the UCT will be missing. A UCT score of <12 shows poorly controlled urticaria, a UCT score of ≥12 presents well controlled urticaria.

  9. Change from baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 [ Time Frame: Week baseline, weeks 12 & 24 for all patients ]
    The minimum possible score is defined as 0 and the maximum possible score is defined as 100. Higher scores indicate worse Quality of Life.

  10. Change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 [ Time Frame: Week baseline, weeks 12 & 24 for all patients ]
    The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

  11. Serum benralizumab concentration and anti-drug antibodies (ADA). [ Time Frame: Week 60 for all patients ]
  12. Change from baseline in weekly Itch Severity Score (ISS7) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ]
    Change from baseline in weekly Itch Severity Score (ISS7) at Week 24 between benralizumab and placebo. The minimum ISS7 is 0 and the maximum is 21, being 21 the most severe score. The baseline ISS7 will be the sum of the ISS during the 7 days prior to day of randomisation. The ISS7 at Week 24 will be the sum of the daily ISS during the previous 7 days.

  13. Proportion of responders (Urticaria Activity Score UAS7≤6) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ]
  14. Change from baseline in weekly hives severity score (HSS7) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ]
    The minimum HSS7 is 0 and the maximum is 21. The baseline HSS7 will be the sum of the HSS during the 7 days prior to day of randomisation. The HSS7 at Week 24 will be the sum of the daily HSS during the previous 7 days.

  15. Proportion of participants with complete Urticaria Activity Score (UAS7) response (UAS7 =0) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ]
  16. Measures of angioedema activity at Week 24 in patients with angioedema at baseline [ Time Frame: Week 24 relative to baseline for all patients ]

    The Urticaria Patient Daily Diary includes a daily yes/no question asking whether the participant experienced angioedema during the past 24 hours. If yes, the participant is asked a follow-up question about how they treated the swelling:

    0 = Did nothing

    1. = Took some prescription or non-prescription medication,
    2. = Called my doctor, nurse or nurse practitioner,
    3. = Went to see my doctor, nurse or nurse practitioner,
    4. = Went to the emergency room at the hospital,
    5. = Was hospitalized. The percentage of angioedema free days will be calculated over the past 7 days.

  17. Change from baseline in Urticaria Control Test (UCT) at Week 24 [ Time Frame: Week 24 relative to baseline for all patients ]
    The minimum and maximum UCT scores are 0 and 16, with 16 points indicating complete disease control. The UCT score will be calculated when all four questions are answered, otherwise the UCT will be missing. A UCT score of <12 shows poorly controlled urticaria, a UCT score of ≥12 presents well controlled urticaria.

  18. Change from baseline in Itch Severity Score (ISS7) at Week 52 [ Time Frame: Week 52 relative to baseline for all patients ]
    Change from baseline in ISS7 at Week 52Itch Severity Score (ISS7) at Week 52 between benralizumab and placebo. The minimum ISS7 is 0 and the maximum is 21, being 21 the most severe score. The baseline ISS7 will be the sum of the ISS during the 7 days prior to day of randomisation. The ISS7 at Week 52 will be the sum of the daily ISS during the previous 7 days.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Informed Consent/Age/Gender

  1. Provision of the signed and dated written informed consent of the participant prior to any mandatory study-specific procedures, sampling, and analyses.
  2. Adult participants≥18 years of age at the time of signing the Informed Consent Form (ICF).

    Type of Participants and Disease

  3. Physician-confirmed diagnosis of CSU (also known as chronic idiopathic urticaria) for at least 6 months prior to screening (Visit 1).
  4. Presence of pruritus and wheals for at least 6 consecutive weeks prior to screening (Visit 1), despite receiving standard of care, which may include second generation H1 antihistamines (at approved or up to 4-times approved doses) as monotherapy or in combination with LTRAs and/or H2 blockers.
  5. Symptomatic during run-in, defined by the following:

    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. Women of childbearing potential (WOCBP) 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 WOCBP study participant and that the vasectomised partner has received medical assessment of the surgical success).
  10. Women not of childbearing potential are defined as women who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Women 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. Women<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 WOCBP.
    2. Women≥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. Doses administered daily or every other day for 5 or more consecutive days of systemic or topical corticosteroids, hydroxychloroquine, methotrexate, cyclosporine, cyclophosphamide, or (IV) immunoglobulin within 30 days before day -14.
  11. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, oral corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained.Short-term treatmentsincluding systemicsteroids for CSU related angioedema may be an exceptionand cases should be discussed with sponsor/study physician.

    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 17 Previously received benralizumab (MEDI-563, FASENRA)
  16. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
  17. Previously received benralizumab (MEDI-563, FASENRA)
  18. 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
  19. Planned major surgical procedures during the conduct of the study
  20. Previous randomisationin the present study
  21. Concurrent enrollment in another clinical trial
  22. AstraZeneca staff involved in the planning and/or conduct of the study
  23. For women only: Currently pregnant, breastfeeding, or lactating women (a) A serum pregnancy test will be done for WOCBP at Visit 1 and a urine pregnancy test must be performed for WOCBP 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04612725


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, Arizona
Research Site Recruiting
Scottsdale, Arizona, United States, 85260
United States, California
Research Site Not yet recruiting
Los Angeles, California, United States, 90025
Research Site Not yet recruiting
Mission Viejo, California, United States, 92691
Research Site Recruiting
Newport Beach, California, United States, 92663
Research Site Not yet recruiting
Westminster, California, United States, 92683
United States, Florida
Research Site Recruiting
Miami, Florida, United States, 33173
Research Site Recruiting
Tampa, Florida, United States, 33606
United States, Georgia
Research Site Recruiting
Columbus, Georgia, United States, 31904
United States, Michigan
Research Site Recruiting
Ypsilanti, Michigan, United States, 48197
United States, Ohio
Research Site Not yet recruiting
Cincinnati, Ohio, United States, 45229
Research Site Recruiting
Cincinnati, Ohio, United States, 45231
United States, Oklahoma
Research Site Recruiting
Norman, Oklahoma, United States, 73071
United States, Texas
Research Site Not yet recruiting
Austin, Texas, United States, 78745
Bulgaria
Research Site Not yet recruiting
Haskovo, Bulgaria, 6300
Research Site Not yet recruiting
Pleven, Bulgaria, 5800
Research Site Not yet recruiting
Ruse, Bulgaria, 7013
Research Site Not yet recruiting
Sofia, Bulgaria, 1000
Research Site Not yet recruiting
Sofia, Bulgaria, 1463
Research Site Not yet recruiting
Sofia, Bulgaria, 1606
Research Site Not yet recruiting
Sofia, Bulgaria, 1680
Germany
Research Site Not yet recruiting
Berlin, Germany, 10117
Research Site Not yet recruiting
Berlin, Germany, 10789
Research Site Not yet recruiting
Dresden, Germany, 01307
Research Site Not yet recruiting
Leipzig, Germany, 04103
Japan
Research Site Not yet recruiting
Hiroshima-shi, Japan, 734-8551
Research Site Recruiting
Kamimashiki-gun, Japan, 861-3101
Research Site Recruiting
Kawasaki-shi, Japan, 211-0063
Research Site Recruiting
Kobe-shi, Japan, 650-0017
Research Site Recruiting
Sakai-shi, Japan, 593-8324
Korea, Republic of
Research Site Not yet recruiting
Gwangju, Korea, Republic of, 501-757
Research Site Not yet recruiting
Seongnam-si, Korea, Republic of, 13620
Research Site Not yet recruiting
Seoul, Korea, Republic of, 03722
Research Site Not yet recruiting
Seoul, Korea, Republic of, 06973
Research Site Not yet recruiting
Seoul, Korea, Republic of, 6591
Poland
Research Site Not yet recruiting
Gdańsk, Poland, 80-546
Research Site Not yet recruiting
Krakow, Poland, 30-033
Research Site Not yet recruiting
Poznan, Poland, 60-529
Research Site Not yet recruiting
Warszawa, Poland, 02-507
Research Site Not yet recruiting
Wrocław, Poland, 50-449
Spain
Research Site Not yet recruiting
Alicante, Spain, 03010
Research Site Not yet recruiting
Barcelona, Spain, 08036
Research Site Not yet recruiting
Barcelona, Spain, 8003
Research Site Not yet recruiting
Cordoba, Spain, 14004
Research Site Not yet recruiting
Madrid, Spain, 28040
Research Site Not yet recruiting
Manises, Spain, 46940
Sponsors and Collaborators
AstraZeneca
Iqvia Pty Ltd
Investigators
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Principal Investigator: Sabine Altrichter, MD Charite Universitaetsmedizin Berlin - Campus Charite Mitte
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04612725    
Other Study ID Numbers: D3259C00001
First Posted: November 3, 2020    Key Record Dates
Last Update Posted: February 10, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: 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
Access Criteria: 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
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
chronic spontaneous urticaria,
skin lesion,
pruritus and wheals
Additional relevant MeSH terms:
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Urticaria
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents