A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist

Study Overview
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Brief Summary
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The purpose of this study is to continue to characterize the safety profile of benralizumab administration and monitor the pharmacodynamic activity of the drug in those asthma patients who remain on treatment for at least 16 weeks and not more than 40 weeks in the predecessor study D3250C00021 (BORA, NCT02258542).

Detailed Description
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This is an open-label safety extension study designed to evaluate the safety and tolerability of a fixed 30 mg dose of benralizumab administered subcutaneously (SC) in severe asthma patients on inhaled corticosteroid and long-acting β2 agonist (ICS-LABA) therapy with or without chronic oral corticosteroids (OCS) and/or other asthma controllers. All patients will receive active drug on the same dosing regimen they received in BORA (NCT02258542). In order to protect the blind of BORA, patients will remain blinded to treatment regimen allocation until they have completed all end of treatment (EOT) assessments in BORA and signed informed consent for participation in this study, after which treatment allocation will be unblinded to both the investigator and the patient.

Official Title
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A Multicenter, Open-label, Safety Extension Study With Benralizumab (MEDI-563) for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist (MELTEMI)

Conditions
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Asthma

Intervention / Treatment
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* Biological: Benralizumab
* Biological: Benralizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent for study participation must be obtained prior to any study related procedures being performed and according to international guidelines and/or applicable European Union guidelines. Female and male patients who have completed at least 16 and not more than 40 weeks in Study D3250C00021. Women of childbearing potential (WOCBP) must agree to use an effective form of birth control throughout the study duration and for 16 weeks after the last dose of Investigational Product (IP) For WOCBP only: Have a negative urine pregnancy test prior to administration of IP at Visit 1. All male patients who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of IP until 16 weeks after their last dose. Exclusion Criteria: Any disorder including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, 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 study or their interpretations Impede the patient's ability to complete the entire duration of study A helminth parasitic infection diagnosed during a predecessor study that has either required hospitalization, has not been treated, has been incompletely treated or has failed to respond to standard of care therapy Any clinically significant change in physical examination, vital signs, ECG, hematology, clinical chemistry, or urinalysis during the predecessor study 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 interfere with the patient's ability to complete the entire duration of the study Current malignancy or malignancy that developed during the predecessor study (subjects that had basal cell carcinoma, localized squamous cell carcinoma of the skin which was resected for cure, or in situ carcinoma of the cervix that has been treated/cured will not be excluded). Receipt of live attenuated vaccines within 30 days prior to initiation of treatment in this study, during the treatment period, and for 16 weeks (5 half-lives) after the last dose of the IP Receipt of immunoglobulin or blood products within 30 days prior to Visit 1 Planned major surgical procedures during the conduct of the study Previous participation in the present study Concurrent enrolment in another drug-related interventional clinical trial AstraZeneca staff involved in the planning and/or conduct of the study Employees of the study center or any other individuals involved with the conduct of the study or immediate family members of such individuals Patients with important protocol deviations in the predecessor study at the discretion of the Sponsor Patients with ongoing serious adverse events (SAEs) from the prior study should not be enrolled into the this extension study until the SAE has resolved

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Benralizumab Arm A<br>Benralizumab administered subcutaneously every 4 weeks | Biological: Benralizumab<br>* Benralizumab administered subcutaneously every 4 weeks<br>|
| Other: Benralizumab Arm B<br>Benralizumab administered subcutaneously every 8 weeks | Biological: Benralizumab<br>* Benralizumab administered subcutaneously every 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Basophils, Full Analysis Set | Change from baseline in hematologic lab parameter of Basophils. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Leukocytes, Full Analysis Set | Change from baseline in hematologic lab parameter of Leukocytes. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Lymphocytes, Full Analysis Set | Change from baseline in hematologic lab parameter of Lymphocytes. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Neutrophils, Full Analysis Set | Change from baseline in hematologic lab parameter of Neutrophils. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Monocytes, Full Analysis Set | Change from baseline in hematologic lab parameter of Monocytes. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Platelets, Full Analysis Set | Change from baseline in hematologic lab parameter of Platelets. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Hematocrit, Full Analysis Set | Change from baseline in hematologic lab parameter of Hematocrit. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Erythrocytes, Full Analysis Set | Change from baseline in hematologic lab parameter of Erythrocytes. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Hemoglobin, Full Analysis Set | Change from baseline in hematologic lab parameter of Hemoglobin. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Alanine Aminotransferase (ALT), Full Analysis Set | Change from baseline in chemistry test ALT. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Aspartate Aminotransferase (AST), Full Analysis Set | Change from baseline in chemistry test AST. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Change From Baseline in Bilirubin, Full Analysis Set | Change from baseline in chemistry test Bilirubin. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Asthma Exacerbations During Study Period | Asthma exacerbation is defined by a worsening of asthma requiring the use of systemic corticosteroids for at least 3 days, and/or an in patient hospitalization, and/or an emergency department or urgent care visit | From week 0 to week 184 in study treatment period and through the follow up period (12 weeks from day of last dose). Number and percentage of participants with asthma exacerbation during this period is presented. | 
| Number of Participants Who Had Health Care Encounter (ie, Hospitalization, Emergency Department Visits, Urgent Care Visits, and All Other Outpatient Visits Due to Asthma) During Study Period | Hospitalizations, Emergency department (ED) visits, urgent care visits and all other outpatient visits due to asthma | From week 0 to week 184 in study treatment period and through the follow up period (12 weeks from day of last dose). Number and percentage of participants with health care encounters during this period is presented. | 
| Change of Blood Eosinophils Count | Change from Baseline to End of Treatment in blood eosinophils count. | From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented. | 
| Number of Participants With Anti-drug Antibodies (ADA) Responses During the Study | Assessments for the presence of ADA and neutralizing antibody (nAb) throughout study | From week 0 to week 184 in study treatment period and plus 12 weeks follow up period | 
| Duration of Exposure | Duration of exposure | From week 0 to week 184 in study treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases