Clinical trial NCT04605094: Efficacy and Safety Study of the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Atopic Dermatitis
Keywords: Moderate to severe atopic dermatitis
pruritus
skin lesion
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2020-10-27
Enrollment: 194
Sex: ALL
Minimum age (years): 12
Maximum age (years): 130
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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
timeFrame: Baseline (Week 0) and at Week 16
Secondary outcomes:
measure: Percentage of Participants Who Experienced 75% Reduction From Baseline in Eczema Area and Severity Index (EASI-75) at Week 16
timeFrame: Baseline (Week 0) and at Week 16
measure: Percentage of Participants Who Experienced 90% Reduction From Baseline in Eczema Area and Severity Index (EASI-90) at Week 16
timeFrame: Baseline (Week 0) and at Week 16
measure: Percentage of Participants With an Improvement of ≥4 or More Points in Peak Pruritus Weekly Score
timeFrame: At Week 16
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Newport Beach
country: United States
facility: Research Site
state: California
city: Bridgeport
country: United States
facility: Research Site
state: Connecticut
city: Fort Myers
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Ypsilanti
country: United States
facility: Research Site
state: Michigan
city: Portsmouth
country: United States
facility: Research Site
state: New Hampshire
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Norman
country: United States
facility: Research Site
state: Oklahoma
city: Sugarloaf
country: United States
facility: Research Site
state: Pennsylvania
city: Kogarah
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Sippy Downs
country: Australia
facility: Research Site
city: Woolloongabba
country: Australia
facility: Research Site
city: Haskovo
country: Bulgaria
facility: Research Site
city: Pleven
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Brno
country: Czechia
facility: Research Site
city: Ostrava-Poruba
country: Czechia
facility: Research Site
city: Ostrava
country: Czechia
facility: Research Site
city: Pardubice
country: Czechia
facility: Research Site
city: Praha 10
country: Czechia
facility: Research Site
city: Praha
country: Czechia
facility: Research Site
city: Brest Cedex 2
country: France
facility: Research Site
city: Lille Cedex
country: France
facility: Research Site
city: Ansan-si
country: Korea, Republic of
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Gwangju
country: Korea, Republic of
facility: Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Yangsan-si
country: Korea, Republic of
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Osielsko
country: Poland
facility: Research Site
city: Poznań
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Alicante
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Manises
country: Spain
facility: Research Site
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Emma Guttman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: