A Study to Evaluate the Onset of Effect and Time Course of Change in Lung Function With Benralizumab in Severe, Uncontrolled Asthma Patients With Eosinophilic Inflammation

Exclusion Criteria

• •1. Clinically important pulmonary disease other than asthma (eg, active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (eg, allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome)
• •2. Life-threatening asthma defined as episodes requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episodes within the 12 months prior to Visit 1.
• •3. Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
• •4. An upper respiratory tract infection or an asthma exacerbation that required treatment with systemic corticosteroids or an increase in regular maintenance dose of OCS during the screening/run-in period prior to randomization Visit 4
• •5. Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could:
• •* Affect the safety of the patient throughout the study
• •* Influence the findings of the studies or their interpretations
• •* Impede the patient's ability to complete the entire duration of study
• •6. Known history of allergy or reaction to any component of the investigational product formulation
• •7. History of anaphylaxis to any biologic therapy
• •8. History of Guillain-Barré syndrome
• •9. 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
• •10. Any clinically significant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening period, which in the opinion of the Investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient's ability to complete entire duration of the study
• •11. Any clinically significant cardiac disease or any electrocardiogram (ECG) abnormality obtained during the screening/run-in period, which in the opinion of the Investigator may put the patient at risk or interfere with study assessments
• •12. History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained
• •13. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Patients with a history of hepatitis B vaccination without history of hepatitis B are allowed to enroll
• •14. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test
• •15. Current smokers or former smokers with a smoking history of ≥10 pack years. A former smoker is defined as a patient who quit smoking at least 6 months prior to Visit 1
• •16. Current malignancy, or history of malignancy, except for:
• •* Patients 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 patient is in remission and curative therapy was completed at least 12 months prior to the date informed consent was obtained.
• •* Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
• •17. Use of immunosuppressive medication (including but not limited to: oral corticosteroids \[for reasons other than asthma\], methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroids or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent
• •18. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥1.5 times the upper limit of normal (ULN) confirmed during screening period
• •19. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
• •20. Receipt of any marketed (eg, omalizumab, mepolizumab etc.) or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer
• •21. Receipt of live attenuated vaccines 30 days prior to the date of randomization
• •22. Receipt of any investigational medication within 30 days or 5 half-lives prior to randomization, whichever is longer
• •23. Previously received benralizumab (MEDI-563)
• •24. Planned surgical procedures during the conduct of the study
• •25. Currently breastfeeding or lactating women
• •26. Previous randomization in the present study
• •27. Concurrent enrolment in another interventional or post-authorization safety study (PASS).
• •28. AstraZeneca staff involved in the planning and/or conduct of the study
• •29. Employees of the study center or any other individuals involved with the conduct of the study or immediate family members of such individuals
• •1\. Greater than/equal to 20% change in mean Pre BD FEV1 value at randomization Visit 4 from the mean pre BD FEV1 calculated from the pre BD FEV1 recorded at Visit 2 and Visit 3