Efficacy and Safety Study of the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis

NCT04605094 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: D3256C00001
• Study Type: interventional
• Target: 194
• Locations: 8 countries
• Sites: 51

Brief Summary

The purpose of the study is to compare the efficacy and safety of benralizumab versus placebo and to compare benralizumab dosing regimens during extension period.

Conditions

Atopic Dermatitis

Keywords

Moderate to severe atopic dermatitis; pruritus; skin lesion

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With an Investigator Global Assessment (IGA) 0/1 and a Decrease in IGA of ≥2 Points at Week 16 Relative to Baseline

  The IGA is an instrument used in clinical studies to rate the severity of AD globally, based on a 5-point scale ranging from 0 = clear; 1 = almost clear; 2 = mild disease; 3 = moderate disease; 4 = severe disease. The IGA used clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment. A higher score indicated greater severity. A responder at Week 16 was defined as having IGA 0/1 and a decrease in IGA of ≥2 points at Week 16 relative to baseline. Participants who withdrew from the study/required rescue therapy after Day 28 were considered as non-responders from the time these events occurred. Baseline was defined as the last recorded value on or prior to the date of randomization.

  Baseline (Week 0) and at Week 16

Secondary Outcomes (3)

• Percentage of Participants Who Experienced 75% Reduction From Baseline in Eczema Area and Severity Index (EASI-75) at Week 16

  Baseline (Week 0) and at Week 16

• Percentage of Participants Who Experienced 90% Reduction From Baseline in Eczema Area and Severity Index (EASI-90) at Week 16

  Baseline (Week 0) and at Week 16

• Percentage of Participants With an Improvement of ≥4 or More Points in Peak Pruritus Weekly Score

  At Week 16

Study Arms (2)

Benralizumab

EXPERIMENTAL

Biological: Benralizumab

Placebo / Benralizumab

EXPERIMENTAL

Biological: Placebo / Benralizumab

Interventions

Benralizumab BIOLOGICAL

Benralizumab by subcutaneous injection until Week 16, and then benralizumab by subcutaneous injection during the extension period.

Also known as: Benralizumab, Benra, Fasenra

Benralizumab

Placebo / Benralizumab BIOLOGICAL

Placebo by subcutaneous injection until Week 16, then benralizumab by subcutaneous injection until Week 52.

Also known as: Benralizumab, Benra, Fasenra

Placebo / Benralizumab

Eligibility Criteria

• Age: 12 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Physician-confirmed diagnosis of AD (according to American Academy of Dermatology Consensus Criteria) that is not adequately controlled with topical medications.
• EASI score of ≥ 12 at screening and ≥ 16 at randomization.
• IGA score of ≥ 3 (on a scale of 0 to 4, in which 3 is moderate and 4 is severe) at screening and at randomization.
• Atopic dermatitis involvement of ≥ 8% body- surface area at screening and ≥ 10% body-surface area at randomization.
• A pruritus numerical rating scale average score for maximum itch intensity of ≥ 4, based on the average of daily pruritus numerical rating scale scores for maximum itch intensity reported during the 7 days prior to randomization.
• Documented recent history (within 6 months prior to screening) of inadequate response to treatment with topical medications, or patients for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks).
• Participants must be willing and able to complete daily PRO assessments:
• Complete at least 70% of daily PRO assessments between Visit 1 and Visit 2 and
• Complete at least 5 of 7 daily PRO assessments in the 7 days prior to Visit 2.
• Females of childbearing potential (FOCBP) must agree to use a highly effective method of birth control (confirmed by the Investigator) from randomization, throughout the study duration, and within 16 weeks after last dose of IP and have a negative serum pregnancy test result on Visit 1.
• Females not of childbearing potential are defined as females who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or who are postmenopausal. Females will be considered postmenopausal if they have been amenorrheic for ≥ 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply:
• Females \< 50 years old will be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and with 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.

You may not qualify if:

• Participants with active dermatological conditions (eg, psoriasis, seborrheic dermatitis, cutaneous lymphoma) other than atopic dermatitis that, in the investigator's opinion, may interfere with the study assessments
• Known active allergic or irritant contact dermatitis that, in the investigator's opinion, may interfere with the study assessments
• Current malignancy, or history of malignancy, with the exception of:
• Participants who have had basal cell carcinoma, localized 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.
• 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, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
• Affect the safety of the participant throughout the study
• Influence the findings of the studies or their interpretations
• 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, hematology, 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 and C (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, hypoalbuminemia, esophageal 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 randomization is acceptable if in the Investigator's opinion the participant does not have an active liver disease and meets other eligibility criteria.

Sponsors & Collaborators

• AstraZeneca: lead
• Iqvia Pty Ltd: collaborator

Study Sites (51)

Research Site

Los Angeles, California, 90025, United States

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Newport Beach, California, 92663, United States

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Bridgeport, Connecticut, 06606, United States

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Fort Myers, Florida, 33912, United States

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Tampa, Florida, 33606, United States

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Tampa, Florida, 33607, United States

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Ypsilanti, Michigan, 48197, United States

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Portsmouth, New Hampshire, 03801, United States

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New York, New York, 10029, United States

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Rochester, New York, 14620, United States

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Cincinnati, Ohio, 45219, United States

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Norman, Oklahoma, 73071, United States

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Sugarloaf, Pennsylvania, 18249, United States

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Kogarah, 2217, Australia

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Parkville, 3050, Australia

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Sippy Downs, 4556, Australia

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Woolloongabba, 04102, Australia

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Haskovo, 6300, Bulgaria

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Pleven, 5800, Bulgaria

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Sofia, 1000, Bulgaria

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Sofia, 1431, Bulgaria

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Brno, 602 00, Czechia

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Ostrava, 702 00, Czechia

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Ostrava-Poruba, 708 52, Czechia

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Pardubice, 530 02, Czechia

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Prague, 100 00, Czechia

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Prague, 110 00, Czechia

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Brest, 29609, France

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Lille, 59037, France

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Krakow, 30-033, Poland

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Lodz, 90-302, Poland

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Osielsko, 86031, Poland

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Poznan, 60-214, Poland

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Warsaw, 01-262, Poland

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Ansan-si, 15355, South Korea

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Daegu, 41944, South Korea

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Gwangju, 61453, South Korea

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Seongnam-si, 13620, South Korea

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Seoul, 04763, South Korea

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Seoul, 05278, South Korea

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Seoul, 05505, South Korea

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Seoul, 06591, South Korea

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Seoul, 06973, South Korea

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Seoul, 07441, South Korea

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Seoul, 5030, South Korea

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Yangsan, 50612, South Korea

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Alicante, 03010, Spain

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Barcelona, 08041, Spain

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Córdoba, 14004, Spain

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Madrid, 28040, Spain

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Manises, 46940, Spain

Location

Related Links

• HILLIER Brochure
• HILLIER Flyer
• HILLIER Patient Brochure
• HILLIER Patient Flyer
• CSR Synopsis
• Statistical Analysis Plan (SAP)
• Protocol

MeSH Terms

Conditions

Dermatitis, Atopic; Pruritus

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Dermatitis; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

The study was terminated as the study did not support the continued development of benralizumab for the indication of AD.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Emma Guttman, MD, PhD

  MOUNT SINAI HOSPITAL

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 1, 2020
• First Posted: October 27, 2020
• Study Start: November 12, 2020
• Primary Completion: April 25, 2022
• Study Completion: September 13, 2022
• Last Updated: August 31, 2023
• Results First Posted: June 27, 2023

Record last verified: 2023-08

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 deidentified 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

ES (5); KR (12); AU (4); US (13); BU (4); CZ (6); PL (5); FR (2)