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

NCT ID: NCT04605094

Last Updated: 2023-08-31

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 194 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-12
• Study Completion Date: 2022-09-13

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.

Detailed Description

The aim of this study is to investigate the use of benralizumab as treatment for patients with moderate to severe atopic dermatitis (AD) who remain symptomatic despite treatment with topical medications. It is proposed that benralizumab will deplete eosinophils from affected skin, improve symptoms of AD, and improve AD-related quality of life. This Phase 2 study is designed to compare the efficacy of treatment with benralizumab versus placebo and compare benralizumab maintenance dosing regimens in the extension period.

Conditions

Atopic Dermatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Benralizumab

Group Type: EXPERIMENTAL

Benralizumab

Intervention Type: BIOLOGICAL

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

Placebo / Benralizumab

Group Type: EXPERIMENTAL

Placebo / Benralizumab

Intervention Type: BIOLOGICAL

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

Interventions

Benralizumab

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

Intervention Type: BIOLOGICAL

Placebo / Benralizumab

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Benralizumab, Benra, Fasenra; Benralizumab, Benra, Fasenra

Eligibility Criteria

Inclusion Criteria

1. Physician-confirmed diagnosis of AD (according to American Academy of Dermatology Consensus Criteria) that is not adequately controlled with topical medications.

2. EASI score of ≥ 12 at screening and ≥ 16 at randomization.

3. 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.

4. Atopic dermatitis involvement of ≥ 8% body- surface area at screening and ≥ 10% body-surface area at randomization.

5. 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.

6. 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).

7. Participants that have applied a stable dose of topical emollient (moisturizer) twice daily for ≥ 7 consecutive days immediately before the randomization visit. (NOTE: See exclusion criterion 11 for limitations regarding emollients)

8. 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.

9. 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.

10. 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:

1. 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.

2. 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.

Exclusion Criteria

1. 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

2. Known active allergic or irritant contact dermatitis that, in the investigator's opinion, may interfere with the study assessments

3. Current malignancy, or history of malignancy, with the exception of:

1. 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.

2. 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, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:

1. Affect the safety of the participant throughout the study

2. Influence the findings of the studies or their interpretations

3. 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, 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

8. Current active liver disease:

1. 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.

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 randomization is 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. Participants who have received treatment for AD with TCS, topical calcineurin inhibitors (TCI), or topical phosphodiesterase-4 (PDE4) inhibitors within the 7 days prior to the randomization visit

11. Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (patients may continue using stable doses of such moisturizers if initiated before the screening visit)

12. Regular use (2 visits per week) of a tanning booth/parlor or phototherapy for AD within 4 weeks prior to the randomization visit

13. Use of immunosuppressive medication including, but not limited to: methotrexate, cyclosporine, azathioprine, systemic corticosteroids within 4 weeks or 5 half-lives prior to the date informed consent is obtained, whichever is longer.

Other

14. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained

15. Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer

16. Receipt of live attenuated vaccines 30 days prior to first dose of IP

17. Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer

18. Previously received benralizumab (MEDI-563, FASENRA)

19. 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

20. Planned elective major surgical procedures during the conduct of the study

21. Previous randomization in the present study

22. Concurrent enrollment in another clinical trial

23. AstraZeneca staff involved in the planning and/or conduct of the study

24. For females only: Currently pregnant, breastfeeding, or lactating females A serum pregnancy test will be done for FOCBP at Visit 1 and a urine pregnancy test must be performed for FOCBP at each subsequent 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Iqvia Pty Ltd

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emma Guttman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

Research Site

Los Angeles, California, United States

Research Site

Newport Beach, California, United States

Research Site

Bridgeport, Connecticut, United States

Research Site

Fort Myers, Florida, United States

Research Site

Tampa, Florida, United States

Research Site

Tampa, Florida, United States

Research Site

Ypsilanti, Michigan, United States

Research Site

Portsmouth, New Hampshire, United States

Research Site

New York, New York, United States

Research Site

Rochester, New York, United States

Research Site

Cincinnati, Ohio, United States

Research Site

Norman, Oklahoma, United States

Research Site

Sugarloaf, Pennsylvania, United States

Research Site

Kogarah, , Australia

Research Site

Parkville, , Australia

Research Site

Sippy Downs, , Australia

Research Site

Woolloongabba, , Australia

Research Site

Haskovo, , Bulgaria

Research Site

Pleven, , Bulgaria

Research Site

Sofia, , Bulgaria

Research Site

Sofia, , Bulgaria

Research Site

Brno, , Czechia

Research Site

Ostrava, , Czechia

Research Site

Ostrava-Poruba, , Czechia

Research Site

Pardubice, , Czechia

Research Site

Prague, , Czechia

Research Site

Prague, , Czechia

Research Site

Brest, , France

Research Site

Lille, , France

Research Site

Krakow, , Poland

Research Site

Lodz, , Poland

Research Site

Osielsko, , Poland

Research Site

Poznan, , Poland

Research Site

Warsaw, , Poland

Research Site

Ansan-si, , South Korea

Research Site

Daegu, , South Korea

Research Site

Gwangju, , South Korea

Research Site

Seongnam-si, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Seoul, , South Korea

Research Site

Yangsan, , South Korea

Research Site

Alicante, , Spain

Research Site

Barcelona, , Spain

Research Site

Córdoba, , Spain

Research Site

Madrid, , Spain

Research Site

Manises, , Spain

Countries

United States; Australia; Bulgaria; Czechia; France; Poland; South Korea; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

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CSR Synopsis

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Statistical Analysis Plan (SAP)

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Protocol

Other Identifiers

D3256C00001

Identifier Type: -

Identifier Source: org_study_id