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

NCT04612725 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: D3259C000012020-000169-17
• Study Type: interventional
• Target: 159
• Locations: 7 countries
• Sites: 40

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.

Conditions

Chronic Spontaneous Urticaria

Keywords

chronic spontaneous urticaria,; skin lesion,; pruritus and wheals

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• LS Mean Change From Baseline in Urticaria Activity Score Over 7 Days (UAS7) at Weeks 12 and 24

  Baseline (Day -1) and Weeks 12 and 24

• LS Mean Change From Baseline in ISS7 at Week 24

  Baseline (Day -1) and Week 24

• Percentage of Responders at Weeks 12 and 24

  Weeks 12 and 24

• LS Mean Change From Baseline in Hives Severity Score Over 7 Days (HSS7) at Weeks 12 and 24

  Baseline (Day -1) and Weeks 12 and 24

• Time to >=5-Point Decrease in ISS7

  From Baseline (Day -1) up to Week 24

Study Arms (5)

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)

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)

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)

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)

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).

Biological: Placebo and Benralizumab

Interventions

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.

Also known as: Benralizumab, Benra, Fasenra

Benralizumab Arm 1; Benralizumab Arm 2; Benralizumab Arm 3; Benralizumab Arm 4

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.

Also known as: Benralizumab, Benra, Fasenra

Placebo and Benralizumab

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Iqvia Pty Ltd: collaborator

Study Sites (40)

Research Site

Scottsdale, Arizona, 85260, United States

Location

Research Site

Los Angeles, California, 90025, United States

Location

Research Site

Mission Viejo, California, 92691, United States

Location

Research Site

Newport Beach, California, 92663, United States

Location

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Miami, Florida, 33173, United States

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Research Site

Tampa, Florida, 33606, United States

Location

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Columbus, Georgia, 31904, United States

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Research Site

Ypsilanti, Michigan, 48197, United States

Location

Research Site

Cincinnati, Ohio, 45229, United States

Location

Research Site

Cincinnati, Ohio, 45236, United States

Location

Research Site

Norman, Oklahoma, 73071, United States

Location

Research Site

Austin, Texas, 78745, United States

Location

Research Site

Haskovo, 6300, Bulgaria

Location

Research Site

Pleven, 5800, Bulgaria

Location

Research Site

Rousse, 7013, Bulgaria

Location

Research Site

Sofia, 1000, Bulgaria

Location

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Sofia, 1463, Bulgaria

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Sofia, 1606, Bulgaria

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Sofia, 1680, Bulgaria

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Berlin, 10117, Germany

Location

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Dresden, 01307, Germany

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Leipzig, 04103, Germany

Location

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Hiroshima, 734-8551, Japan

Location

Research Site

Kamimashikigun,, 861-3106, Japan

Location

Research Site

Kawasaki-shi, 211-0063, Japan

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Kobe, 650-0017, Japan

Location

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Sakaishi, 593-8324, Japan

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Gdansk, 80-546, Poland

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Krakow, 30-033, Poland

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Poznan, 60-214, Poland

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Warsaw, 02-507, Poland

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Wroclaw, 50-449, Poland

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Research Site

Seoul, 03722, South Korea

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Research Site

Seoul, 06973, South Korea

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Research Site

Seoul, 6591, South Korea

Location

Research Site

Alicante, 03010, Spain

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Barcelona, 8003, Spain

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Research Site

Córdoba, 14004, Spain

Location

Research Site

Madrid, 28040, Spain

Location

Research Site

Manises, 46940, Spain

Location

Related Links

• ARROYO Patient Brochure
• ARROYO Patient Flyer
• Redacted CSR synopsis

MeSH Terms

Conditions

Chronic Urticaria; Pruritus; Urticaria

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Manifestations; Signs and Symptoms

Limitations and Caveats

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.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Sabine Altrichter, MD

  Charite Universitaetsmedizin Berlin - Campus Charite Mitte

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: November 3, 2020
• Study Start: October 27, 2020
• Primary Completion: October 13, 2022
• Study Completion: March 28, 2023
• Last Updated: March 13, 2024
• Results First Posted: March 13, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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

Locations

US (12); BU (7); JP (5); KR (3); PL (5); ES (5); DE (3)