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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04605094
Recruitment Status : Recruiting
First Posted : October 27, 2020
Last Update Posted : September 9, 2021
Sponsor:
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Atopic Dermatitis Biological: Benralizumab Biological: Placebo / Benralizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2 Multinational, Randomized, Double-blind, Parallel-group, 16-week Placebo-controlled Study With a 36-Week Extension to Investigate the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis Despite Treatment With Topical Medications (The HILLIER Study)
Actual Study Start Date : November 12, 2020
Estimated Primary Completion Date : February 17, 2022
Estimated Study Completion Date : December 22, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: Benralizumab Biological: Benralizumab
Benralizumab by subcutaneous injection until Week 16, and then benralizumab by subcutaneous injection during the extension period.
Other Name: Benralizumab, Benra, Fasenra

Experimental: Placebo / Benralizumab Biological: Placebo / Benralizumab
Placebo by subcutaneous injection until Week 16, then benralizumab by subcutaneous injection until Week 52.
Other Name: Benralizumab, Benra, Fasenra




Primary Outcome Measures :
  1. Proportion of patients with an IGA 0/1 and a decrease in IGA of ≥ 2 points at Week 16 relative to baseline [ Time Frame: Week 16 for all patients ]
    Scale Title: Investigator Global Assessment Score (IGA) Minimum Value: 0 - Clear Maximum Value: 4 - Severe High score means a worse outcome


Secondary Outcome Measures :
  1. Proportion of patients with skin clearance (EASI-75) [ Time Frame: Week 16 for all patients ]

    Scale Title: Eczema Area and Severity Index (EASI)

    Area Score:

    Minimum Value: 0 - No active eczema in this region Maximum Value: 6 - The entire region is affected by eczema

    Severity Score:

    Minimum Value: 0 - None Maximum Value: 3 - Severe High score means a worse outcome


  2. Serum benralizumab concentration and anti-drug antibodies (ADA) [ Time Frame: Week 16 for all patients ]
  3. Proportion of patients with skin clearance (EASI-90) [ Time Frame: Week 16 for all patients ]

    Scale Title: Eczema Area and Severity Index (EASI)

    Area Score:

    Minimum Value: 0 - No active eczema in this region Maximum Value: 6 - The entire region is affected by eczema

    Severity Score:

    Minimum Value: 0 - None Maximum Value: 3 - Severe High score means a worse outcome


  4. Proportion of patients with an improvement of ≥ 4 or more points in peak pruritus weekly score [ Time Frame: Week 16 for all patients ]
    Scale Title: Peak Pruritus Rating Scale Minimum Value: 0 - No itch Maximum Value: 10 - Worst itch imaginable High score means a worse outcome

  5. Change from baseline in DLQI and CDLQI [ Time Frame: Week 16 for all patients ]

    Scale Title: Dermatology Life Quality Index Minimum Value - Not at all/Not relevant Maximum Value - Very much

    Scale Title: Children's Dermatology Life Quality Index Minimum Value - Not at all Maximum Value - Very much High score means a worse outcome




Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 130 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04605094


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Iqvia Pty Ltd
Investigators
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Principal Investigator: Emma Guttman, MD, PhD MOUNT SINAI HOSPITAL
Additional Information:
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04605094    
Other Study ID Numbers: D3256C00001
First Posted: October 27, 2020    Key Record Dates
Last Update Posted: September 9, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting Materials: Study Protocol
Statistical Analysis Plan (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.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Moderate to severe atopic dermatitis
pruritus
skin lesion
Additional relevant MeSH terms:
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Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents