Efficacy and Safety Study of the Use of Benralizumab for Patients With Moderate to Severe Atopic Dermatitis
Condition: Atopic Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis; Eczema
Intervention: Benralizumab; Placebo / Benralizumab
Intervention description: Benralizumab by subcutaneous injection until Week 16, and then benralizumab by subcutaneous injection during the extension period.; Placebo by subcutaneous injection until Week 16, then benralizumab by subcutaneous injection until Week 52.
Intervention MeSH terms: Benralizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 194.0
Sex: All
Minimum age: 12 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Moderate to severe atopic dermatitis; pruritus; skin lesion

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.
    

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.