Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02258542
Recruitment Status : Completed
First Posted : October 7, 2014
Results First Posted : February 6, 2019
Last Update Posted : August 21, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Asthma Biological: Benralizumab Phase 3

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.

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2133 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
Official Title: A Multicentre, Double-blind, Randomized, Parallel Group, Phase 3 Safety Extension Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Asthmatic Adults and Adolescents on Inhaled Corticosteroid Plus Long-acting β2 Agonist (BORA)
Actual Study Start Date : November 19, 2014
Actual Primary Completion Date : October 18, 2017
Actual Study Completion Date : July 2, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Benralizumab Arm A
Benralizumab administered subcutaneously
 Biological: Benralizumab
Benralizumab administered subcutaneously
Experimental: Benralizumab Arm B
Benralizumab administered subcutaneously
 Biological: Benralizumab
Benralizumab administered subcutaneously


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Change From Baseline in Basophils, Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in hematologic lab parameter of Basophils.

  2. Change From Baseline in Basophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of Basophils.

  3. Change From Baseline in Leukocytes, Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in hematologic lab parameter of Leukocytes.

  4. Change From Baseline in Leukocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of Leukocytes.

  5. Change From Baseline in Lymphocytes, Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in hematologic lab parameter of Lymphocytes.

  6. Change From Baseline in Lymphocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of Lymphocytes.

  7. Change From Baseline in Neutrophils, Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in hematologic lab parameter of Neutrophils.

  8. Change From Baseline in Neutrophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of Neutrophils.

  9. Change From Baseline in Eosinophils, Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in hematologic lab parameter of Eosinophils.

  10. Change From Baseline in Eosinophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of Eosinophils.

  11. Change From Baseline in Alanine Aminotransferase (ALT), Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in chemistry tests ALT.

  12. Change From Baseline in ALT, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of ALT.

  13. Change From Baseline in Aspartate Aminotransferase (AST), Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in chemistry tests AST.

  14. Change From Baseline in AST, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of AST.

  15. Change From Baseline in Bilirubin, Full Analysis Set, Excluding MELTEMI Patients [ Time Frame: Week 56 ]
    Change from baseline in chemistry test Bilirubin.

  16. Change From Baseline in Bilirubin, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline in hematologic lab parameter of Bilirubin.


Secondary Outcome Measures :
  1. Number of Overall Patients With Asthma Exacerbations During Study Period [ Time Frame: 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

  2. Number of Overall Patients With Asthma Exacerbations During Study Period, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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

  3. Change From Baseline in Pre-bronchodilator FEV1 (L) [ Time Frame: Week 56 ]
    Change from baseline to Week 56 in Pre-bronchodilator Forced expiratory volume in 1 second (FEV1).

  4. Change From Baseline in Pre-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline to Week 108 in Pre-bronchodilator Forced expiratory volume in 1 second (FEV1).

  5. Change From Baseline in Post-bronchodilator FEV1 (L) [ Time Frame: Week 56 ]
    Change from baseline to Week 56 in Post-bronchodilator Forced expiratory volume in 1 second (FEV1).

  6. Change From Baseline in Post-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Week 108 ]
    Change from baseline to Week 108 in Post-bronchodilator Forced expiratory volume in 1 second (FEV1).

  7. Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients [ Time Frame: 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.

  8. Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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.

  9. Change From Baseline in Total Score of Asthma Related and General Health-related Quality of Life Questionnaire (AQLQ(S)+12) [ Time Frame: 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.

  10. Change From Baseline in Total Score of Asthma Related and General Health-related Quality of Life Questionnaire (AQLQ(S)+12), Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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.

  11. Change of Blood Eosinophil Levels' Measurement in Overall Patients [ Time Frame: Week 56 ]
    Change from baseline to Week 56 in Blood eosinophils

  12. Change of Blood Eosinophil Levels' Measurement in Adolescents Patients (SIROCCO/CALIMA). [ Time Frame: Week 108 ]
    Change from baseline to Week 108 in Blood eosinophils.

  13. Change From Baseline in EQ-5D-5L Visual Analog Scale [ Time Frame: 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.

  14. Change From Baseline in EQ-5D-5L Visual Analog Scale, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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.

  15. Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI) [ Time Frame: 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.

  16. Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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.

  17. Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ) [ Time Frame: 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.

  18. Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ), Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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.

  19. Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI) [ Time Frame: 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.

  20. Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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.

  21. 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 [ Time Frame: 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

  22. 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) [ Time Frame: Baseline and Week 108 ]
    Hospitalizations, ED visits, urgent care visits and all other outpatient visits due to asthma

  23. Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study [ Time Frame: Week 0 and Week 56 ]
    Endpoint: Pharmacokinetic (PK) parameters

  24. Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: Baseline and Week 108 ]
    Endpoint: Pharmacokinetic (PK) parameters

  25. Number of Patients With Anti-drug Antibodies (ADA) Responses During the Study [ Time Frame: 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

  26. Number of Patients With Anti-drug Antibodies (ADA) Responses During the Study, Adolescents Only (SIROCCO/CALIMA) [ Time Frame: 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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria

  1. Informed consent (and/or assent as applicable locally) for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent(s)/guardian(s)) and according to international guidelines and/or applicable European Union guidelines.
  2. Female and male patients who completed the double-blind treatment period in a predecessor study on benralizumab or matching placebo.
  3. Women of childbearing potential (WOCBP) must agree to use an effective form of birth control throughout the study duration and for 16 weeks after last dose of Investigational Product (IP).
  4. For WOCBP only: Have a negative urine pregnancy test prior to administration of Investigational Product (IP) at Visit 1.
  5. 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

  1. Any disorder including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, 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 studies or their interpretations
    • Impede the patient's ability to complete the entire duration of study
  2. A helminth parasitic infection diagnosed during a predecessor study that has either not been treated, has been incompletely treated or has failed to respond to standard of care therapy
  3. Any clinically significant change in physical examination, vital signs, electrocardiogram (ECG), haematology, clinical chemistry, or urinalysis during a 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
  4. Current malignancy or malignancy that developed during a 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).
  5. 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 investigational product
  6. Receipt of immunoglobulin or blood products within 30 days prior to Visit 1
  7. Planned major surgical procedures during the conduct of the study
  8. Previous participation in the present study
  9. Concurrent enrolment in another clinical trial
  10. AstraZeneca staff involved in the planning and/or conduct of the study
  11. Employees of the study centre or any other individuals involved with the conduct of the study or immediate family members of such individuals
  12. Patients with major protocol deviations in any of the predecessor studies at the discretion of the Sponsor
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02258542


Locations
Show Show 431 study locations
Sponsors and Collaborators
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: William W. Busse, M.D., Professor of Medicine Allergy, Pulmonary, and Critical Care Medicine 600 Highland Avenue; Madison, WI
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Study Protocol  [PDF] December 16, 2016
Statistical Analysis Plan  [PDF] December 11, 2017

More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02258542    
Other Study ID Numbers: D3250C00021
U1111-1162-2422 ( Other Identifier: WHO )
First Posted: October 7, 2014    Key Record Dates
Results First Posted: February 6, 2019
Last Update Posted: August 21, 2019
Last Verified: July 2019
Keywords provided by AstraZeneca:
Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases
Additional relevant MeSH terms:
Layout table for MeSH terms
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
 Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents