Efficacy and Safety Study of the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis
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| ClinicalTrials.gov Identifier: NCT04605094 |
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Recruitment Status :
Terminated
(The study did not meet the primary endpoint.)
First Posted : October 27, 2020
Last Update Posted : January 5, 2023
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Sponsor:
AstraZeneca
Collaborator:
Iqvia Pty Ltd
Information provided by (Responsible Party):
AstraZeneca
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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 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 194 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 |
| Actual Primary Completion Date : | April 25, 2022 |
| Actual Study Completion Date : | September 13, 2022 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Atopic dermatitis
MedlinePlus related topics:
Eczema
Drug Information available for:
Benralizumab
| 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 :
- 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 :
- 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
- 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
- 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
- Safety [ Time Frame: up to week 16 ]Frequency of AEs, SAEs, deaths and AE's leading to discontinuation of investigational product.
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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:
- 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 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)
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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.
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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.
Exclusion Criteria:
- 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
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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.
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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
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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.
- A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test Prior/concomitant Therapy
- 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
- 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)
- Regular use (2 visits per week) of a tanning booth/parlor or phototherapy for AD within 4 weeks prior to the randomization visit
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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
- Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
- 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
- Receipt of live attenuated vaccines 30 days prior to first dose of IP
- Receipt of any investigational nonbiologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer
- Previously received benralizumab (MEDI-563, FASENRA)
- 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
- Planned elective major surgical procedures during the conduct of the study
- Previous randomization in the present study
- Concurrent enrollment in another clinical trial
- AstraZeneca staff involved in the planning and/or conduct of the study
- 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
Locations
Show 51 study locations
Sponsors and Collaborators
AstraZeneca
Iqvia Pty Ltd
Investigators
| Principal Investigator: | Emma Guttman, MD, PhD | MOUNT SINAI HOSPITAL |
Additional Information:
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT04605094 |
| Other Study ID Numbers: |
D3256C00001 |
| First Posted: | October 27, 2020 Key Record Dates |
| Last Update Posted: | January 5, 2023 |
| Last Verified: | December 2022 |
| 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 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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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 |