Study to Evaluate Efficacy and Safety of Benralizumab in Reducing Oral Corticosteroid Use in Adult Patients With Severe Asthma

Phase 3

Completed

Conditions: Asthma

Interventions: Biological: Benralizumab

Registration Number: NCT03557307

Lead Sponsor: AstraZeneca

Brief Summary: This is a study designed to evaluate efficacy and safety of Benralizumab in reducing the Oral Corticosteroid (OCS) use in adult patients with severe asthma who are receiving OCS with or without additional asthma controller medications.

Detailed Description: This is an open-label, multicenter study designed to evaluate efficacy and safety of reducing daily oral corticosteroid (OCS) use after initiation of 30 mg dose of benralizumab administered subcutaneously (SC) in patients with severe eosinophilic asthma receiving high-dose inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) and OCS with or without additional asthma controller(s).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 598

Inclusion Criteria

Peripheral blood eosinophil count of ≥150 cells/μL assessed by central lab at Visit 1 or ≥ 300 cells/μL in the past 12 months
History of physician diagnosed asthma requiring continuous treatment with high dose ICS (high-dose ICS is budesonide/formoterol HFA ≥640/18 per day or equivalent, fluticasone propionate DPI > 500/day or equivalent, or authorized generics for these products) plus LABA for at least 6 months prior to Visit 1. The ICS and LABA can be contained within a combination product or given by separate inhalers. The ICS can also be given via nebulized solution for inhalation.
Chronic oral corticosteroid therapy equivalent to a daily dose of at least 5 mg of prednisone, for at least 3 continuous months directly preceding Visit 1.
Patient should be on a stable OCS dose for at least 4 weeks prior to Visit 1.
Non-smokers, current smokers or former smokers with a smoking history of < or =20 pack-years at Visit 1

Exclusion Criteria

Clinically important pulmonary disease other than asthma or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts
Known history of allergy or reaction to the study drug formulation
History of anaphylaxis to any biologic therapy
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
Asthma exacerbation requiring use of systemic corticosteroids, or an increase in maintenance dose of OCS, or acute upper/lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to Visit 2 (first benralizumab dose)
A history of known immunodeficiency disorder including history of a positive human immunodeficiency virus (HIV) test
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥3 times the upper limit of normal (ULN) confirmed at Visit 1.
Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained
Coincident primary adrenal failure (Addison's disease) or irreversible secondary hypoadrenalism due to another independent cause (e.g. pituitary tumour or its treatment)
Co-existent inflammatory conditions for which chronic OCS doses are part of their maintenance treatment such as Giant Cell Arteritis, Polymyalgia Rheumatica
Exclusion from genetic research may be for any of the exclusion criteria specified in the main study or allogeneic bone marrow transplant, Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample collection
Current night-shift workers

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Benralizumab	Benralizumab	Benralizumab subcutaneous injection

Primary Outcome Measures

Name	Time	Method
Patients Who Achieve 100% Reduction in Daily OCS Dose	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)	Patients who achieve 100% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Patients Who Achieve 100% Reduction or a Daily OCS Dose of <=5mg	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)	Patients who achieve 100% reduction or a daily OCS dose of \<=5mg, if reason for no further OCS reduction is Adrenal Insufficiency, that are sustained over at least 4 weeks without worsening of asthma

Secondary Outcome Measures

Name	Time	Method
Patients Who Achieve a Daily OCS of ≤5mg	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)	Patients who achieve a daily OCS dose of ≤5 mg (regardless of reason for no further OCS reduction), that are sustained over at least 4 weeks without worsening of asthma
Patients Who Achieve a ≥90%, ≥75%, and ≥50% Reduction in Daily OCS Dose	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)	Patients who achieve a ≥90%, ≥75%, and ≥50% reduction in daily OCS dose that are sustained over at least 4 weeks without worsening of asthma
Change From Baseline in Average Daily OCS Dose (mg)	Baseline to end of OCS reduction phase, an average of approximately 200 days (The duration of the OCS reduction phase may vary based on asthma exacerbations, asthma worsening, HPA integrity , or other safety issues altering the OCS titration schedule.)	Change from baseline in average daily OCS dose (mg) from start of OCS reduction to end of the OCS reduction phase