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NCT04612725: ARROYO

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

Terminated Phase 2 Results posted Last updated 13 March 2024
What this trial tests

Phase 2 trial testing Benralizumab in Chronic Spontaneous Urticaria in 159 participants. Terminated before completion.

Timeline
27 October 2020
Primary endpoint
13 October 2022
28 March 2023

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment159
Start date27 October 2020
Primary completion13 October 2022
Estimated completion28 March 2023
Sites40 locations across Japan, Germany, Poland, South Korea, Bulgaria, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 130, any sex, with Chronic Spontaneous Urticaria. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Least Square (LS) Mean Change From Baseline in Itch Severity Score Over 7 Days (ISS7) at Week 12 Primary · 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.

GroupValue95% CI
Benralizumab 30 mg-7.50-8.94 – -6.05
Benralizumab 60 mg-8.28-9.76 – -6.80
Placebo-6.49-8.24 – -4.74
LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24 Secondary · Baseline (Day -1) and Weeks 12 and 24

The UPDD was completed twice daily (morning and evening) to capture key measures of urticaria disease activity including the UAS7. Participants were asked to document the number of hives they experienced on a scale ranging from 0 to 3 (where 0= none, 1= mild \[1 - 6 hives/12 hour\], 2= moderate \[7 - 12 hives/12 hour\] and 3= intense \[(\> 12 hives/12 hour\]). The UAS7 is the sum of UAS for the previous 7 days, that is, the sum of ISS7 and HSS7. The UAS7 represents urticaria severity on a scale from 0 (minimum) to 42 (maximum). Higher scores indicate greater severity of urticaria symptoms. Bas

Week 12
GroupValue95% CI
Benralizumab 30 mg-14.48-17.58 – -11.38
Benralizumab 60 mg-16.77-19.94 – -13.59
Placebo-12.41-16.17 – -8.65
Week 24
GroupValue95% CI
Benralizumab 30 mg-17.99-21.29 – -14.68
Benralizumab 60 mg-19.17-22.51 – -15.83
Placebo-15.43-19.43 – -11.44
LS Mean Change From Baseline in ISS7 at Week 24 Secondary · Baseline (Day -1) and Week 24

The UPDD was completed twice daily (morning and evening) to capture key measures of urticaria disease activity including the ISS. The ISS represents severity on a scale ranging from 0 to 3 (where 0= none, 1= mild, 2= moderate and 3= severe). The ISS7 is the sum of ISS for the previous 7 days. The ISS7 represents itch severity on a scale ranging from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of itch. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.

GroupValue95% CI
Benralizumab 30 mg-9.19-10.77 – -7.61
Benralizumab 60 mg-9.33-10.93 – -7.73
Placebo-7.57-9.48 – -5.66
Percentage of Responders at Weeks 12 and 24 Secondary · 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.

Week 12
GroupValue95% CI
Benralizumab 30 mg22.0
Benralizumab 60 mg21.4
Placebo10.0
Week 24
GroupValue95% CI
Benralizumab 30 mg28.8
Benralizumab 60 mg37.5
Placebo27.5
LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24 Secondary · Baseline (Day -1) and Weeks 12 and 24

The UPDD was completed twice daily (morning and evening) to capture key measures of urticaria disease activity including the HSS7. Participants were asked to document the number of hives they experienced on a scale ranging from 0 to 3 (where 0= none, 1= mild \[1 - 6 hives/12 hour\], 2= moderate \[7 - 12 hives/12 hour\] and 3= intense \[(\> 12 hives/12 hour\]). The HSS7 is the sum of hives severity score for the previous 7 days. The HSS7 represents hives severity on a scale from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of hives. Baseline was defined as the sum of th

Week 12
GroupValue95% CI
Benralizumab 30 mg-7.03-8.84 – -5.22
Benralizumab 60 mg-8.47-10.32 – -6.62
Placebo-5.87-8.06 – -3.68
Week 24
GroupValue95% CI
Benralizumab 30 mg-8.88-10.76 – -7.00
Benralizumab 60 mg-9.81-11.71 – -7.91
Placebo-7.82-10.09 – -5.54
Time to >=5-Point Decrease in ISS7 Secondary · From Baseline (Day -1) up to Week 24

The time to \>=5-point decrease (clinically relevant decrease) in ISS7 was reported. The ISS7 is the sum of ISS for the previous 7 days. The ISS7 represents itch severity on a scale ranging from 0 (minimum) to 21 (maximum). Higher scores indicate greater intensity of itch.

GroupValue95% CI
Benralizumab 30 mg3.02.0 – 5.0
Benralizumab 60 mg2.02.0 – 3.0
Placebo8.03.0 – 11.0
Percentage of Participants With Complete UAS7 Response at Weeks 12 and 24 Secondary · 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.

Week 12
GroupValue95% CI
Benralizumab 30 mg11.9
Benralizumab 60 mg7.1
Placebo10.0
Week 24
GroupValue95% CI
Benralizumab 30 mg16.9
Benralizumab 60 mg21.4
Placebo20.0
Mean Percentage of Angioedema-Free Days Over the Past 7 Days at Weeks 12 and 24 Secondary · 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.

Week 12
GroupValue95% CI
Benralizumab 30 mg77.50± 35.990
Benralizumab 60 mg85.63± 32.435
Placebo81.93± 34.548
Week 24
GroupValue95% CI
Benralizumab 30 mg78.50± 36.992
Benralizumab 60 mg91.33± 27.032
Placebo86.79± 31.798
LS Mean Change From Baseline in Urticaria Control Test (UCT) at Weeks 12 and 24 Secondary · Baseline (Day -1) and Weeks 12 and 24

Urticaria disease control was assessed by the UCT using the electronic participant-reported outcome device. The UCT has a retrospective approach using a recall period of 4 weeks and responses on 5-point Likert scales with score ranging from 0 to 4 for each question. Subsequently, the scores for all 4 questions were summed up. The UCT scale range from 0 (minimum) to 16 (maximum). Higher scores indicate better disease control.

Week 12
GroupValue95% CI
Benralizumab 30 mg4.743.71 – 5.76
Benralizumab 60 mg6.115.05 – 7.17
Placebo5.023.78 – 6.26
Week 24
GroupValue95% CI
Benralizumab 30 mg5.244.04 – 6.45
Benralizumab 60 mg6.875.65 – 8.09
Placebo5.884.44 – 7.32
LS Mean Change From Baseline in Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) at Weeks 12 and 24 Secondary · Baseline (Day -1) and Weeks 12 and 24

The CU-Q2oL is a 23-item assessment of CSU-specific health-related quality of life. Participants were asked to rate their CSU symptoms and the impact of their symptoms over the last 2 weeks on several domains: pruritus, swelling, impact on life activities, sleep problems, limits, and looks. The questions were scored as 1= not at all, 2= a little, 3= moderately, 4= very much, 5= extremely. The scores were transformed into percentages of the maximum possible score. The CU-Q2oL scale range from 0 (minimum) to 100 (maximum). Higher scores indicate greater impact of urticaria on health-related qual

Week 12
GroupValue95% CI
Benralizumab 30 mg-16.47-20.10 – -12.84
Benralizumab 60 mg-20.34-24.09 – -16.60
Placebo-18.10-22.46 – -13.74
Week 24
GroupValue95% CI
Benralizumab 30 mg-17.60-21.81 – -13.40
Benralizumab 60 mg-22.11-26.38 – -17.84
Placebo-19.07-24.09 – -14.05
LS Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Weeks 12 and 24 Secondary · Baseline (Day -1) and Weeks 12 and 24

The DLQI is a 10-item assessment of dermatology-specific health-related quality of life. Participants were asked to rate their symptoms and the impact of their symptoms over the last week on several domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. The questions (except question 7) were scored on a 4-point Likert scale: 0= not at all, 1= a little, 2= a lot, 3= very much. Scoring question 7, the first part asked: 'Over the last week, has your skin prevented you from working or studying?' Scoring was for response of 0= not relevant

Week 12
GroupValue95% CI
Benralizumab 30 mg-7.58-9.18 – -5.98
Benralizumab 60 mg-9.31-10.96 – -7.66
Placebo-8.06-9.98 – -6.14
Week 24
GroupValue95% CI
Benralizumab 30 mg-8.13-9.84 – -6.42
Benralizumab 60 mg-10.25-11.98 – -8.51
Placebo-9.37-11.41 – -7.33
Serum Concentration of Benralizumab Secondary · Pre-dose on Weeks 4, 12 and 24

Blood samples were collected to determine the serum concentration of benralizumab.

Week 4
GroupValue95% CI
Benralizumab 30 mg990.515± 448.6799
Benralizumab 60 mg2167.606± 991.7509
Week 12
GroupValue95% CI
Benralizumab 30 mg1321.373± 740.5070
Benralizumab 60 mg3145.352± 1577.6726
Week 24
GroupValue95% CI
Benralizumab 30 mg1372.806± 883.5830
Benralizumab 60 mg1638.810± 946.9466
PlaceboNA± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Treatment-emergent adverse events (TEAEs) are reported from the first dose administration up to 30days after the last dose of study drug, a maximum of approximately 57 weeks.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Double-blind Period: Benralizumab 30 mg Q4W
Serious: 3/59 (5%)
Deaths: 0/59
Double-blind Period: Benralizumab 60 mg Q4W
Serious: 1/56 (2%)
Deaths: 0/56
Double-blind Period: Placebo
Serious: 0/40 (0%)
Deaths: 0/40
Extension Period: Benralizumab 30 mg Q4W
Serious: 0/49 (0%)
Deaths: 0/49
Extension Period: Benralizumab 30 mg Q8W
Serious: 3/54 (6%)
Deaths: 0/54
Extension Period: Placebo to Benralizumab
Serious: 1/37 (3%)
Deaths: 0/37

Serious adverse events (8 terms)

ReactionSystemDouble-blind Period: Benra…Double-blind Period: Benra…Double-blind Period: PlaceboExtension Period: Benraliz…Extension Period: Benraliz…Extension Period: Placebo …
UreterolithiasisRenal and urinary disorders
Biliary colicHepatobiliary disorders
HypersensitivityImmune system disorders
Subarachnoid haemorrhageNervous system disorders
AsthmaRespiratory, thoracic and mediastinal disorders
UrticariaSkin and subcutaneous tissue disorders
Meniscus injuryInjury, poisoning and procedural complications
Bladder cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Other adverse events (8 terms — click to expand)

ReactionSystemDouble-blind Period: Benra…Double-blind Period: Benra…Double-blind Period: PlaceboExtension Period: Benraliz…Extension Period: Benraliz…Extension Period: Placebo …
COVID-19Infections and infestations
NasopharyngitisInfections and infestations
HeadacheNervous system disorders
SinusitisInfections and infestations
Ligament sprainInjury, poisoning and procedural complications
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Ureterolithiasis, Biliary colic, Hypersensitivity, Subarachnoid haemorrhage, Asthma, Urticaria, Meniscus injury, Bladder cancer.

Data from ClinicalTrials.gov NCT04612725 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Current and Emerging Therapies for Chronic Spontaneous Urticaria: A Narrative Review.
    Yosipovitch G, Biazus Soares G, Mahmoud O. · · 2023 · cited 20× · PMID 37386330 · DOI 10.1007/s13555-023-00972-6
  2. Advances in Biologic Therapies for Allergic Diseases: Current Trends, Emerging Agents, and Future Perspectives.
    Alska E, Łaszczych D, Napiórkowska-Baran K, Szymczak B, et al · · 2025 · cited 13× · PMID 40004611 · DOI 10.3390/jcm14041079
  3. Use of biologics in chronic spontaneous urticaria - beyond omalizumab therapy?
    Metz M, Maurer M. · · 2021 · cited 13× · PMID 33615122 · DOI 10.5414/alx02204e
  4. Therapies for Chronic Spontaneous Urticaria: Present and Future Developments.
    Asero R, Calzari P, Vaienti S, Cugno M. · · 2024 · cited 10× · PMID 39598410 · DOI 10.3390/ph17111499
  5. Monoclonal Antibodies in Treating Chronic Spontaneous Urticaria: New Drugs for an Old Disease.
    Manti S, Giallongo A, Papale M, Parisi GF, et al · · 2022 · cited 7× · PMID 35956071 · DOI 10.3390/jcm11154453
  6. The Role of Benralizumab in Eosinophilic Immune Dysfunctions: A Case Report-Based Literature Review.
    Gomes M, Mendes A, Ferreira F, Branco J, et al · · 2023 · cited 3× · PMID 37138643 · DOI 10.1155/2023/8832242
  7. Biologics for Non-Cancer Dermatological Diseases: Analysis on China's Clinical Trial Registration Trend From 2016 to 2020.
    Zhu B, Liu Y, Li J, Ni Q, et al · · 2022 · cited 2× · PMID 35529441 · DOI 10.3389/fphar.2022.817065
  8. Comparing novel treatments in chronic spontaneous urticaria: A critical appraisal of Bruton's tyrosine kinase inhibitors versus anti-cytokine biologics in clinical trials.
    Diamanti A, Tontini C, Bulfone-Paus S. · · 2025 · cited 1× · PMID 40148228 · DOI 10.1002/clt2.70053

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