A Safety Extension Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Asthmatic Adults and Adolescents on Inhaled Corticosteroid Plus LABA

Phase 3

Completed

Conditions: Asthma

Interventions: Biological: Benralizumab

Registration Number: NCT02258542

Lead Sponsor: AstraZeneca

Brief Summary: The purpose of this study is to characterize the safety profile of benralizumab administration in asthma patients who have completed one of the three predecessor studies: D3250C00017, D3250C00018 or D3250C00020.

Detailed Description: After a minimum of 1200 patients have been enrolled in this study, subsequent patients (up to a maximum of 2200 total for the study), who complete a minimum of 16 weeks, and no more than 40 weeks, in this study, will be given the option to transition to an open-label safety extension study, Study D3250C00037 (MELTEMI).

Adolescent patients, patients from Japan and South Korea, and any patient who chooses not to enter Study D3250C00037 will remain in this study through IPD or EOT and FU.

At the time of the first interim analysis in Japanese patients, the study regimen for all patients will become unblinded to AstraZeneca for data analysis purposes. Study conduct and blinding at the site and patient level will remain unchanged.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2133

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Benralizumab Arm A	Benralizumab	Benralizumab administered subcutaneously
Benralizumab Arm B	Benralizumab	Benralizumab administered subcutaneously

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Basophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of Basophils.
Change From Baseline in Lymphocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of Lymphocytes.
Change From Baseline in Basophils, Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in hematologic lab parameter of Basophils.
Change From Baseline in Leukocytes, Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in hematologic lab parameter of Leukocytes.
Change From Baseline in Leukocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of Leukocytes.
Change From Baseline in Lymphocytes, Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in hematologic lab parameter of Lymphocytes.
Change From Baseline in Neutrophils, Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in hematologic lab parameter of Neutrophils.
Change From Baseline in Neutrophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of Neutrophils.
Change From Baseline in Eosinophils, Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in hematologic lab parameter of Eosinophils.
Change From Baseline in Eosinophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of Eosinophils.
Change From Baseline in Alanine Aminotransferase (ALT), Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in chemistry tests ALT.
Change From Baseline in ALT, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of ALT.
Change From Baseline in Aspartate Aminotransferase (AST), Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in chemistry tests AST.
Change From Baseline in AST, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of AST.
Change From Baseline in Bilirubin, Full Analysis Set, Excluding MELTEMI Patients	Week 56	Change from baseline in chemistry test Bilirubin.
Change From Baseline in Bilirubin, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline in hematologic lab parameter of Bilirubin.

Secondary Outcome Measures

Name	Time	Method
Number of Overall Patients With Asthma Exacerbations During Study Period	From week 0 to week 56 in study treatment period and through the follow up period (16 weeks from day of last dose)	Annual asthma exacerbation rate, where an 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
Number of Overall Patients With Asthma Exacerbations During Study Period, Adolescents Only (SIROCCO/CALIMA)	From week 0 to week 108 in study treatment period and through the follow up period (16 weeks from day of last dose)	Annual asthma exacerbation rate, where an 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
Change From Baseline in Pre-bronchodilator FEV1 (L)	Week 56	Change from baseline to Week 56 in Pre-bronchodilator Forced expiratory volume in 1 second (FEV1).
Change From Baseline in Pre-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline to Week 108 in Pre-bronchodilator Forced expiratory volume in 1 second (FEV1).
Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ)	Week 56	The WPAI (+CIQ) is a 10-item questionnaire that assesses productivity and activity impairment over the previous week. The questionnaire includes hours missed from work/school due to asthma, degree health affected productivity while at work/school, as well as the degree to which health affected regular activities other than work or school. The questionnaire related to the previous 7 days. Classroom productivity loss is calculated with sum of hours missed for classes due to health problem and hours that affected due to health problem in classes, divided by sum of hours missed due to health problem and hours actually attended classes, presented by percentage.
Change From Baseline in Post-bronchodilator FEV1 (L)	Week 56	Change from baseline to Week 56 in Post-bronchodilator Forced expiratory volume in 1 second (FEV1).
Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients	Week 56	Asthma Control Questionnaire 6 (ACQ-6) contains 1 bronchodilator use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score was the mean of the responses.
Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients, Adolescents Only (SIROCCO/CALIMA)	Week 108	Asthma Control Questionnaire 6 (ACQ-6) contains 1 bronchodilator use question and 5 symptom questions. Questions were weighted equally and scored from 0 (totally controlled) to 6 (severely uncontrolled). The mean ACQ-6 score was the mean of the responses.
Change From Baseline in Total Score of Asthma Related and General Health-related Quality of Life Questionnaire (AQLQ(S)+12)	Week 56	Standardised Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) comprises 4 separate domains (symptoms, activity limitations, emotional function, and environmental stimuli). It contains 32 questions on a 7 point scale ranging from 7 (no impairment) to 1 (severe impairment); total score is an average of all questions. An increase in score indicates improvement.
Change From Baseline in Total Score of Asthma Related and General Health-related Quality of Life Questionnaire (AQLQ(S)+12), Adolescents Only (SIROCCO/CALIMA)	Week 108	Standardised Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ(S)+12) comprises 4 separate domains (symptoms, activity limitations, emotional function, and environmental stimuli). It contains 32 questions on a 7 point scale ranging from 7 (no impairment) to 1 (severe impairment); total score is an average of all questions. An increase in score indicates improvement.
Change From Baseline in EQ-5D-5L Visual Analog Scale, Adolescents Only (SIROCCO/CALIMA)	Week 108	The questionnaire included a VAS, where the patient was asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state; thus, an increase in VAS score indicated improvement.
Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA)	Week 108	The WPAI+CIQ is a 10-item questionnaire that assesses productivity and activity impairment over the previous week. The questionnaire includes hours missed from work/school due to asthma, degree health affected productivity while at work/school, as well as the degree to which health affected regular activities other than work or school. The questionnaire related to the previous 7 days. Work productivity loss is calculated with sum of hours missed at work due to health problem and hours that affected due to health problem at work, divided by sum of hours missed due to health problem and hours actually worked, presented by percentage.
Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ), Adolescents Only (SIROCCO/CALIMA)	Week 108	The WPAI (+CIQ) is a 10-item questionnaire that assesses productivity and activity impairment over the previous week. The questionnaire includes hours missed from work/school due to asthma, degree health affected productivity while at work/school, as well as the degree to which health affected regular activities other than work or school. The questionnaire related to the previous 7 days. Classroom productivity loss is calculated with sum of hours missed for classes due to health problem and hours that affected due to health problem in classes, divided by sum of hours missed due to health problem and hours actually attended classes, presented by percentage.
Number of Patients Who Had Health Care Encounter (ie, Hospitalization, Emergency Department Visits, Urgent Care Visits, and All Other Outpatient Visits Due to Asthma) During Study Period	From week 0 to week 68 in study treatment period and through the follow up period (16 weeks from day of last dose)	Hospitalizations, Emergency department (ED) visits, urgent care visits and all other outpatient visits due to asthma
Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study	Week 0 and Week 56	Endpoint: Pharmacokinetic (PK) parameters
Number of Patients With Anti-drug Antibodies (ADA) Responses During the Study, Adolescents Only (SIROCCO/CALIMA)	From week 0 to week 108 study treatment period (adults) and plus 16 weeks the follow up period; From week 0 to week 108-week in study treatment period (adolescents) and plus 16 weeks the follow up period	Assessments for the presence of ADA and nAb throughout study
Change From Baseline in Post-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA)	Week 108	Change from baseline to Week 108 in Post-bronchodilator Forced expiratory volume in 1 second (FEV1).
Change of Blood Eosinophil Levels' Measurement in Overall Patients	Week 56	Change from baseline to Week 56 in Blood eosinophils
Change of Blood Eosinophil Levels' Measurement in Adolescents Patients (SIROCCO/CALIMA).	Week 108	Change from baseline to Week 108 in Blood eosinophils.
Change From Baseline in EQ-5D-5L Visual Analog Scale	Week 56	The questionnaire included a visual analog scale (VAS) score, where the patient was asked to rate current health status on a scale of 0 to 100, with 0 being the worst imaginable health state; thus, an increase in VAS score indicated improvement.
Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI)	Week 68	The WPAI+CIQ is a 10-item questionnaire that assesses productivity and activity impairment over the previous week. The questionnaire includes hours missed from work/school due to asthma, degree health affected productivity while at work/school, as well as the degree to which health affected regular activities other than work or school. The questionnaire related to the previous 7 days. Work productivity loss is calculated with sum of hours missed at work due to health problem and hours that affected due to health problem at work, divided by sum of hours missed due to health problem and hours actually worked, presented by percentage.
Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI)	Week 68	The WPAI+CIQ is a 10-item questionnaire that assesses productivity and activity impairment over the previous week. The questionnaire includes hours missed from work/school due to asthma, degree health affected productivity while at work/school, as well as the degree to which health affected regular activities other than work or school. The questionnaire related to the previous 7 days. The WPAI+CIQ outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Number of Patients With Anti-drug Antibodies (ADA) Responses During the Study	From week 0 to week 56 in study treatment period (adults) and plus 16 weeks the follow up period; From week 0 to week 108-week in study treatment period (adolescents) and plus 16 weeks the follow up period	Assessments for the presence of ADA and neutralizing antibody (nAb) throughout study
Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA)	Week 108	The WPAI+CIQ is a 10-item questionnaire that assesses productivity and activity impairment over the previous week. The questionnaire includes hours missed from work/school due to asthma, degree health affected productivity while at work/school, as well as the degree to which health affected regular activities other than work or school. The questionnaire related to the previous 7 days. The WPAI+CIQ outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity.
Number of Patients Who Had Health Care Encounter (ie, Hospitalization, Emergency Department Visits, Urgent Care Visits, and All Other Outpatient Visits Due to Asthma) During Study Period, Adolescents Only (SIROCCO/CALIMA)	Baseline and Week 108	Hospitalizations, ED visits, urgent care visits and all other outpatient visits due to asthma
Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study, Adolescents Only (SIROCCO/CALIMA)	Baseline and Week 108	Endpoint: Pharmacokinetic (PK) parameters