A Study of the Safety and Effectiveness of Benralizumab to Treat Patients With Severe Uncontrolled Asthma.

Inclusion Criteria

• Female and male patients aged 18 to 75 years inclusively at the time of Visit 1 with a history of physician-diagnosed asthma requiring treatment with medium-to-high dose Inhaled Corticosteroids (ICS) plus asthma controller, for at least 12 months prior to Visit 1.
• Documented current treatment with high daily doses of ICS plus at least one other asthma controller for at least 3 months prior to Visit 1.
• History of at least 2 asthma exacerbations while on ICS plus another asthma controller that required treatment with systemic corticosteroids (IM, IV, or oral) in the 12 months prior to Visit 1.
• ACQ6 score ≥1.5 at Visit 1.
• Screening pre-bronchodilator (pre-BD) FEV1 of 10% when averaged over 7 continuous days during the study run-in period
• An increase in FEV1 of ≥12% and 200 mL after a therapeutic trial of systemic corticosteroid (eg, OCS), given outside of an asthma exacerbation, documented in the 12 months prior enrolment Visit 1.
• Airway hyper-responsiveness (methacholine: PC20 of <8 mg/mL, histamine: PD20 of <7.8 μmol, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 months prior to randomization Visit 4.
• Peripheral blood eosinophil count either:
• 300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2

OR

≥150 to <300 cells/μL assessed by central laboratory at either Visit 1 or Visit 2, IF ≥1 of the following 5 clinical criteria (a to e) is met:

• Using maintenance OCS (daily or every other day OCS requirement in order to maintain asthma control; maximum total daily dose 20 mg prednisone or equivalent) at screening
• History of nasal polyposis
• Age of asthma onset ≥18 years
• Three or more documented exacerbations requiring systemic corticosteroid treatment during the 12 months prior to screening
• Pre-bronchodilator forced vital capacity <65% of predicted, as assessed at Visit 2 (note that screening pre-BD FEV1 Inclusion Criterion #6 must still be satisfied)

For inclusion in the open label ANDHI IP sub study patients should meet the following criteria:

• Patients study must have completed ANDHI EOT Visit 11.
• Written informed consent must also be obtained prior to any study related procedures being performed in the open label ANDHI IP sub study.
• Patients who have received any approved or investigational targeted biologic for the treatment of asthma (e.g. commercial mepolizumab, reslizumab, benralizumab) may be included if the last dose is ≥ 2 months of Visit 13.

Exclusion Criteria

• Clinically important pulmonary disease other than asthma
• Acute upper or lower respiratory infections within 30 days prior to the date informed consent.
• 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.
• History of alcohol or drug abuse within 12 months prior to the date informed consent is obtained.
• A history of known immunodeficiency disorder.
• Current smokers or former smokers with a smoking history of ≥10 pack years.
• Previously received benralizumab (MEDI-563).
• Receipt of any investigational medication as part of a research study within approximately 5 half-lives prior to randomization.
• Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
• Receipt of live attenuated vaccines 30 days prior to the date of randomization; other types of vaccines are allowed.
• Concurrent enrolment in another interventional or post-authorization safety study

Exclusion criteria for the open label ANDHI IP sub study:

Patients should not enter the open label ANDHI IP sub study if any of the following exclusion criteria are fulfilled. Each exclusion criterion should be reviewed in all potential participants, including those who transition directly from the double-blind period and those with a delay between completing the EOT Vis