A study of the safety and effectiveness of benralizumab to treat patients with severe uncontrolled asthma. - ANDHI

Inclusion Criteria

• 1. 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.
• 2. 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.
• 3. 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.
• 4. ACQ6 score ≥1.5 at Visit 1.
• 5. Screening pre-bronchodilator (pre-BD) FEV1 of <80% predicted at Visit 2.
• 6. Excessive variability in lung function by satisfying ≥ 1 of the following criteria:
• a) Airway reversibility (FEV1 ≥12%) using a short-acting bronchodilator demonstrated at Visit 2 or Visit 3.
• b) Airway reversibility to short-acting bronchodilator (FEV1 ≥12%) documented during the 12 months prior to enrolment Visit 1.
• c) Daily diurnal peak flow variability of >10% when averaged over 7 continuous days during the study run-in period
• d) 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.
• e) 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.
• 7. 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:
• (a) 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
• (b) History of nasal polyposis
• (c) Age of asthma onset ≥18 years
• (d) Three or more documented exacerbations requiring systemic corticosteroid treatment during the 12 months prior to screening
• (e) 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:
• 1.Patients study must have completed ANDHI EOT Visit 11.
• 2.Written informed consent must also be obtained prior to any study related
• procedures being performed in the open label ANDHI IP sub study.
• 3.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.