Chronic Spontaneous UrticariaPhase 2ARROYONCT04612725
A Study to Investigate the Use of Benralizumab in Patients With Chronic Spontaneous Urticaria Who Are Symptomatic Despite the Use of Antihistamines (ARROYO)
A Phase 2 study testing Benralizumab in people with Chronic Spontaneous Urticaria, run by AstraZeneca at 40 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Chronic Spontaneous Urticaria
- What is being tested?
- Benralizumab
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 159 participants
- Where
- 40 sitesin 7 countries
- Study dates
- 27 Oct 2020to 28 Mar 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Symptomatic during run-in, defined by the following:
- UAS7 total score of ≥ 16 with an ISS7 of ≥ 8, during the 7 days prior to randomisation (Visit 2)
- In-clinic UAS total score of ≥ 4 on at least one of the screening days.
- 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:
- Complete at least 80% of daily PRO assessments between Visit 1 and Visit 2 and
- Complete at least 6 of 7 daily PRO assessments in the 7 days prior to Visit 2.
- 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:
- Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal.
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable.
- Intrauterine device.
- Intrauterine hormone-releasing system.
- Bilateral tubal occlusion or ligation.
- 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).
- 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).
- 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:
- 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.
- 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.
Who cannot join
- 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.
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- 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:
- 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.
- 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.
- 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.
Trial locations and contacts
40 sites in 7 countries.
40 sites in 7 countries
United States12 sites
Research Site
Austin, Texas, 78745
Research Site
Cincinnati, Ohio, 45229
Research Site
Cincinnati, Ohio, 45236
Research Site
Columbus, Georgia, 31904
Research Site
Los Angeles, California, 90025
Research Site
Miami, Florida, 33173
Research Site
Mission Viejo, California, 92691
Research Site
Newport Beach, California, 92663
Research Site
Norman, Oklahoma, 73071
Research Site
Scottsdale, Arizona, 85260
Research Site
Tampa, Florida, 33606
Research Site
Ypsilanti, Michigan, 48197
Bulgaria7 sites
Research Site
Haskovo, 6300
Research Site
Pleven, 5800
Research Site
Rousse, 7013
Research Site
Sofia, 1000
Research Site
Sofia, 1463
Research Site
Sofia, 1606
Research Site
Sofia, 1680
Japan5 sites
Research Site
Hiroshima, 734-8551
Research Site
Kamimashikigun,, 861-3106
Research Site
Kawasaki-shi, 211-0063
Research Site
Kobe, 650-0017
Research Site
Sakaishi, 593-8324
Poland5 sites
Research Site
Gdansk, 80-546
Research Site
Krakow, 30-033
Research Site
Poznan, 60-214
Research Site
Warsaw, 02-507
Research Site
Wroclaw, 50-449
Spain5 sites
Research Site
Alicante, 03010
Research Site
Barcelona, 8003
Research Site
Córdoba, 14004
Research Site
Madrid, 28040
Research Site
Manises, 46940
Germany3 sites
Research Site
Berlin, 10117
Research Site
Dresden, 01307
Research Site
Leipzig, 04103
South Korea3 sites
Research Site
Seoul, 03722
Research Site
Seoul, 06973
Research Site
Seoul, 6591
About this study
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)
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.
Read the 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.
- Conditions
- Chronic Spontaneous Urticaria
- Being tested
- Benralizumab, Placebo and Benralizumab
- Keywords
- chronic spontaneous urticaria,, skin lesion,, pruritus and wheals
- Medical subject headings
- Chronic Urticaria, Pruritus, Urticaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BenralizumabBiological
Also called Benralizumab, Benra, Fasenra
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.
Placebo and BenralizumabBiological
Also called Benralizumab, Benra, Fasenra
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Biological: Benralizumab |
| 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) Receives: Biological: Benralizumab |
| 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) Receives: Biological: Benralizumab |
| 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) Receives: Biological: Benralizumab |
| 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). Receives: Biological: Placebo and Benralizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline (Day -1) and Week 12
Secondary outcomes (12)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline (Day -1) and Weeks 12 and 24
Serum Concentration of Benralizumab
Blood samples were collected to determine the serum concentration of benralizumab.
Measured: 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).
Measured: Pre-dose on Weeks 12 and 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Nov 2020
- Study start27 Oct 2020
- Primary completion13 Oct 2022
- Study completion28 Mar 2023
Why it stopped: Study did not meet primary endpoint
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Spontaneous UrticariaStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 159 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Responsible party
- Sponsor
- Investigators
- Sabine Altrichter, MD, Principal investigator, Charite Universitaetsmedizin Berlin - Campus Charite Mitte
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04612725
- Sponsor's protocol ID
- D3259C00001
- Other IDs
- 2020-000169-17
- Acronym
- ARROYO
- Status last verified
- Mar 2024
- First submitted
- 18 Sep 2020
- Last updated
- 13 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04612725
- Acronym / sponsor ID
- ARROYO / D3259C00001
- Conditions
- Chronic Spontaneous Urticaria
- Keywords
- chronic spontaneous urticaria,, skin lesion,, pruritus and wheals
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study did not meet primary endpoint
- Enrolment
- 159 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- IQVIA Pty Ltd
- Study start
- 27 Oct 2020 (actual)
- Primary completion
- 13 Oct 2022 (actual)
- Study completion
- 28 Mar 2023 (actual)
- First posted
- 3 Nov 2020 (actual)
- Results
- Posted 13 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Benralizumab Arm 1 | Experimental | Biological: BenralizumabBenralizumab 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 | Biological: BenralizumabBenralizumab 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 | Biological: BenralizumabBenralizumab 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 | Biological: BenralizumabBenralizumab 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 | Biological: Placebo and BenralizumabPlacebo regimen A until Week 24, benralizumab Dose B regiment A until Week 36, and Dose B regimen B until Week 52 (n=40). |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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).
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BenralizumabAlso: Benralizumab, Benra, Fasenra2 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. | Biological | Benralizumab Arm 1, Benralizumab Arm 2, Benralizumab Arm 3, Benralizumab Arm 4 |
| Placebo and BenralizumabAlso: Benralizumab, Benra, Fasenra2 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. | Biological | Placebo and Benralizumab |
Primary outcome
Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12
Time frame: Baseline (Day -1) and Week 12
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.
12 secondary outcomes
LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24
Time frame: Baseline (Day -1) and Weeks 12 and 24
LS Mean Change From Baseline in ISS7 at Week 24
Time frame: Baseline (Day -1) and Week 24
Percentage of Responders at Weeks 12 and 24
Time frame: Weeks 12 and 24
LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24
Time frame: Baseline (Day -1) and Weeks 12 and 24
Time to >=5-Point Decrease in ISS7
Time frame: From Baseline (Day -1) up to Week 24
Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24
Time frame: Weeks 12 and 24
Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24
Time frame: Weeks 12 and 24
LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24
Time frame: Baseline (Day -1) and Weeks 12 and 24
LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24
Time frame: Baseline (Day -1) and Weeks 12 and 24
LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24
Time frame: Baseline (Day -1) and Weeks 12 and 24
Serum Concentration of Benralizumab
Time frame: Pre-dose on Weeks 4, 12 and 24
Number of Participants With Anti-Drug Antibody (ADA) Response to Benralizumab
Time frame: Pre-dose on Weeks 12 and 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- ARROYO Patient BrochureLink provided by the sponsor.
- ARROYO Patient FlyerLink provided by the sponsor.
- Redacted CSR synopsisLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sabine Altrichter, MD principal investigator
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
40 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Benralizumab in people with Chronic Spontaneous Urticaria, run by AstraZeneca at 40 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 40 sites in United States, Bulgaria, Japan, Poland, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 (time frame: Baseline (Day -1) and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024; AzTrials last refreshed its copy on 8 Nov 2026.