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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 2,133
- 试验地点
- 431
- 主要终点
- Change From Baseline in Lymphocytes, Full Analysis Set, Excluding MELTEMI Patients
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Female and male patients who completed the double-blind treatment period in a predecessor study on benralizumab or matching placebo.
- •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).
- •For WOCBP only: Have a negative urine pregnancy test prior to administration of Investigational Product (IP) at Visit
- •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.
排除标准
- •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
- •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
- •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
- •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).
- •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
- •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 clinical trial
- •AstraZeneca staff involved in the planning and/or conduct of the study
- •Employees of the study centre or any other individuals involved with the conduct of the study or immediate family members of such individuals
- •Patients with major protocol deviations in any of the predecessor studies at the discretion of the Sponsor
研究组 & 干预措施
Benralizumab Arm A
Benralizumab administered subcutaneously
干预措施: Benralizumab (Biological)
Benralizumab Arm B
Benralizumab administered subcutaneously
干预措施: Benralizumab (Biological)
结局指标
主要结局
Change From Baseline in Lymphocytes, Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in hematologic lab parameter of Lymphocytes.
Change From Baseline in Leukocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of Leukocytes.
Change From Baseline in Eosinophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of Eosinophils.
Change From Baseline in Alanine Aminotransferase (ALT), Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in chemistry tests ALT.
Change From Baseline in ALT, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of ALT.
Change From Baseline in Aspartate Aminotransferase (AST), Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in chemistry tests AST.
Change From Baseline in AST, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of AST.
Change From Baseline in Bilirubin, Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in chemistry test Bilirubin.
Change From Baseline in Basophils, Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in hematologic lab parameter of Basophils.
Change From Baseline in Leukocytes, Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in hematologic lab parameter of Leukocytes.
Change From Baseline in Basophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of Basophils.
Change From Baseline in Lymphocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of Lymphocytes.
Change From Baseline in Neutrophils, Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in hematologic lab parameter of Neutrophils.
Change From Baseline in Neutrophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of Neutrophils.
Change From Baseline in Eosinophils, Full Analysis Set, Excluding MELTEMI Patients
时间窗: Week 56
Change from baseline in hematologic lab parameter of Eosinophils.
Change From Baseline in Bilirubin, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA)
时间窗: Week 108
Change from baseline in hematologic lab parameter of Bilirubin.
次要结局
- 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))
- 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))
- Change From Baseline in Pre-bronchodilator FEV1 (L)(Week 56)
- Change From Baseline in Pre-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA)(Week 108)
- Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ)(Week 56)
- Change From Baseline in Post-bronchodilator FEV1 (L)(Week 56)
- Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients(Week 56)
- Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients, Adolescents Only (SIROCCO/CALIMA)(Week 108)
- Change From Baseline in Total Score of Asthma Related and General Health-related Quality of Life Questionnaire (AQLQ(S)+12)(Week 56)
- 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)
- Change From Baseline in EQ-5D-5L Visual Analog Scale, Adolescents Only (SIROCCO/CALIMA)(Week 108)
- Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA)(Week 108)
- Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ), Adolescents Only (SIROCCO/CALIMA)(Week 108)
- 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))
- Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study(Week 0 and Week 56)
- 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)
- Change From Baseline in Post-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA)(Week 108)
- Change of Blood Eosinophil Levels' Measurement in Overall Patients(Week 56)
- Change of Blood Eosinophil Levels' Measurement in Adolescents Patients (SIROCCO/CALIMA).(Week 108)
- Change From Baseline in EQ-5D-5L Visual Analog Scale(Week 56)
- Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI)(Week 68)
- Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI)(Week 68)
- 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)
- Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA)(Week 108)
- 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)
- Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study, Adolescents Only (SIROCCO/CALIMA)(Baseline and Week 108)