Effect of Benralizumab in Atopic Dermatitis

Inclusion Criteria:

1. Male and female patients 18 through 65 years of age.

2. Women of childbearing potential (WOCBP) must not be actively seeking pregnancy, andmust use an effective form of birth control (confirmed by the Investigator).Effective forms of birth control include: true sexual abstinence, a vasectomizedsexual partner, Implanon, female sterilization by tubal occlusion, any effectiveintrauterine device (IUD)/ levonorgestrel Intrauterine system (IUS), Depo-Provera™injections, oral contraceptive, and Evra Patch™ or Nuvaring™. WOCBP must agree touse effective method of birth control, as defined above, from enrolment, throughoutthe study duration and within 16 weeks after last dose of IP. They must demonstratea negative serum pregnancy test at screening and demonstrate a negative urinepregnancy test immediately before each dose of study drug or placebo. Women not ofchildbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who arepostmenopausal. Women will be considered postmenopausal if they have beenamenorrheic for 12 months prior to the planned date of randomization without analternative medical cause. The following age-specific requirements apply:

• Women <50 years old would be considered postmenopausal if they have beenamenorrheic for 12 months or more following cessation of exogenous hormonaltreatment and follicle stimulating hormone (FSH) levels in the postmenopausalrange.

• Women ≥50 years old would be considered postmenopausal if they have beenamenorrheic for 12 months or more following cessation of all exogenous hormonaltreatment.

3. All male patients who are sexually active must agree to use an acceptable method ofcontraception (condom with or without spermicide, vasectomy) from the first dose ofinvestigational product (IP) until 16 weeks after their last dose.

4. General good health

5. Moderate to severe atopic dermatitis

6. Able to understand and give written informed consent and has signed a writteninformed consent form approved by the investigator's Research Ethics Board (REB)

The following inclusion criteria must be met for entry into the dosing phase of the study:

1. Positive skin-prick test to common aeroallergens (including cat, dust mite, grass,pollen)

2. Positive late cutaneous response to intradermal allergen challenge

Exclusion Criteria:

1. History of anaphylaxis to any biologic therapy or vaccine

2. History of clinically significant hypotensive episodes or symptoms of fainting,dizziness, or light headedness, as judged by the investigator

3. Any history or symptoms of cardiovascular disease, particularly coronary arterydisease, arrhythmias, hypertension, or congestive heart failure

4. Any history or symptoms of significant neurologic disease, including transientischemic attack (TIA), stroke, seizure disorder, or behavioral disturbances

5. Any history or symptoms of clinically significant autoimmune disease

6. Any history of clinically significant haematologic abnormality, includingcoagulopathy or any history of chronic treatment with anticoagulants (e.g. warfarin,etc) or antiplatelet agent (e.g, aspirin, etc)

7. Clinically significant abnormalities in laboratory test results at enrolment andduring the screening period (including complete blood count, coagulation, chemistrypanel and urinalysis) unless judged not significant by the investigator.

8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 timesthe upper limit of normal (ULN) confirmed during screening period

9. Being pregnant or lactating or have positive serum pregnancy test at enrolment orpositive urine pregnancy test during the study

10. Concomitant disease or condition which could interfere with the conduct of thestudy, or for which the treatment might interfere with the conduct of the study, orwhich would, in the opinion of the investigator, pose an unacceptable risk to thepatient in this study, including, but not limited to, cancer, alcoholism, drugdependency or abuse, or psychiatric disease

11. Severe concomitant illness(es) that, in the investigator's judgment, would adverselyaffect the patient's participation in the study

12. Presence of skin comorbidities that may interfere with study assessments

13. History of cancer: Patients who have had basal cell carcinoma, localized squamouscell carcinoma of the skin, or in situ carcinoma of the cervix are eligible providedthat the subject is in remission and curative therapy was completed at least 12months prior to the date informed consent. Patients who have had other malignanciesare eligible provided that the subject is in remission and curative therapy wascompleted at least 5 years prior to the date of informed consent.

14. Patient who has a scheduled in-patient surgery or hospitalization during the study.

15. History of Guillain-Barré syndrome

16. A helminth parasitic infection diagnosed within 24 weeks prior to the date informedconsent is obtained that has not been treated with, or has failed to respond tostandard of care therapy

17. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or apositive medical history for hepatitis B or C. Patients with a history of hepatitisB vaccination without history of hepatitis B are allowed to enrol

18. A history of known immunodeficiency disorder including a positive humanimmunodeficiency virus (HIV) test

19. Receipt of immunoglobulin or blood products within 30 days prior to the dateinformed consent is obtained

20. Receipt of any marketed (eg omalizumab) or investigational biologic within 4 monthsor 5 half-lives prior to randomization is obtained, whichever is longer

21. Treatment with an investigational drug within 8 weeks or within 5 half-lives (ifknown), whichever is longer, before the baseline visit

22. Any allergen immunotherapy within 4 months prior to or throughout the study.

23. Having used any of the following treatments within 4 weeks before the Day -2baseline visit, or any condition that, in the opinion of the investigator, is likelyto require such treatment(s) during study:

24. Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids,cyclosporine, mycophenolate-mofetil, interferon gamma (IFN-γ), Janus kinaseinhibitors, azathioprine, methotrexate, etc.)

25. Phototherapy for AD

26. Any cell-depleting agents including but not limited to rituximab: within 6 monthsbefore the baseline visit, or until lymphocyte count returns to normal, whichever islonger

27. Initiation of treatment of AD with prescription moisturizers or moisturizerscontaining additives such as ceramide, hyaluronic acid, urea, or filaggrindegradation products during the screening period (patients may continue using stabledoses of such moisturizers if initiated before the screening visit)

28. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeksof the baseline visit

29. Active chronic or acute infection requiring treatment with systemic antibiotics,antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before thebaseline visit, or superficial skin infections within 1 week before the baselinevisit. Note: patients may be re-screened after infection resolves

30. Known or suspected history of immunosuppression, including history of invasiveopportunistic infections (eg, histoplasmosis, listeriosis, coccidioidomycosis,pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent,recurrent, or prolonged infections, per investigator judgment

31. Planned or anticipated major surgical procedure during the patient's participationin this study

32. Receipt of live attenuated vaccines 30 days prior to the date of randomization.Receipt of inactive/killed vaccinations (eg, inactive influenza) are allowedprovided they are not administered within 1 week before/after any IP administration.

33. Patient is a member of the investigational team or his/her immediate family

34. Pregnant woman

35. Previously received benralizumab (MEDI-563)