Phase 3
Completed N=2,123
A Safety Extension Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Asthmatic Adults and Adolescents on Inhaled Corticosteroid Plus LABA
Source: ClinicalTrials.gov NCT02258542 ↗Enrolled (actual)
2,123
Serious AEs
12.8%
Results posted
Feb 2019
Primary outcomePrimary: Change From Baseline in Basophils, Full Analysis Set, Excluding MELTEMI Patients — -0.005; -0.005; -0.007; -0.005 10^9 cells/L
◆ Published Evidence
Highly cited
309citations · ~44 / year
Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial.
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.
Linked Publications (2)
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Long-term safety and efficacy of benralizumab in patients with severe, uncontrolled asthma: 1-year results from the BORA phase 3 extension trial.
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Benralizumab for adolescent patients with severe, eosinophilic asthma: Safety and efficacy after 3 years of treatment.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Basophils, Full Analysis Set, Excluding MELTEMI Patients |
-0.005; -0.005; -0.007; -0.005 | — |
| PRIMARY Change From Baseline in Basophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
-0.006; 0.001 | — |
| PRIMARY Change From Baseline in Leukocytes, Full Analysis Set, Excluding MELTEMI Patients |
-0.344; -0.128; -0.808; -0.507 | — |
| PRIMARY Change From Baseline in Leukocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
-0.487; -0.079 | — |
| PRIMARY Change From Baseline in Lymphocytes, Full Analysis Set, Excluding MELTEMI Patients |
-0.032; 0.003; -0.093; 0.007 | — |
| PRIMARY Change From Baseline in Lymphocytes, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
-0.180; -0.070 | — |
| PRIMARY Change From Baseline in Neutrophils, Full Analysis Set, Excluding MELTEMI Patients |
-0.171; 0.013; -0.501; -0.368 | — |
| PRIMARY Change From Baseline in Neutrophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
-0.451; 0.242 | — |
| PRIMARY Change From Baseline in Eosinophils, Full Analysis Set, Excluding MELTEMI Patients |
-0.1220; -0.1271; -0.1451; -0.1664 | — |
| PRIMARY Change From Baseline in Eosinophils, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
-0.1294; -0.1838 | — |
| PRIMARY Change From Baseline in Alanine Aminotransferase (ALT), Full Analysis Set, Excluding MELTEMI Patients |
-0.007; 0.017; -0.064; -0.023 | — |
| PRIMARY Change From Baseline in ALT, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
0.048; 0.034 | — |
| PRIMARY Change From Baseline in Aspartate Aminotransferase (AST), Full Analysis Set, Excluding MELTEMI Patients |
-0.005; 0.004; -0.027; -0.026 | — |
| PRIMARY Change From Baseline in AST, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
-0.006; -0.013 | — |
| PRIMARY Change From Baseline in Bilirubin, Full Analysis Set, Excluding MELTEMI Patients |
0.187; 0.391; 0.146; 0.279 | — |
| PRIMARY Change From Baseline in Bilirubin, Full Analysis Set, Adolescents Only (SIROCCO/CALIMA) |
2.221; 0.202 | — |
| SECONDARY Number of Overall Patients With Asthma Exacerbations During Study Period |
99; 60; 159; 104; 66; 170 | — |
| SECONDARY Number of Overall Patients With Asthma Exacerbations During Study Period, Adolescents Only (SIROCCO/CALIMA) |
2; 6; 8; 3; 5; 8 | — |
| SECONDARY Change From Baseline in Pre-bronchodilator FEV1 (L) |
-0.006; 0.131; 0.038; 0.019; 0.081; 0.040 | — |
| SECONDARY Change From Baseline in Pre-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA) |
0.205; -0.189; -0.020; 0.578; 0.413; 0.496 | — |
| SECONDARY Change From Baseline in Post-bronchodilator FEV1 (L) |
-0.066; 0.089; -0.015; -0.029; 0.045; -0.004 | — |
| SECONDARY Change From Baseline in Post-bronchodilator FEV1 (L), Adolescents Only (SIROCCO/CALIMA) |
-0.062; -0.305; -0.201; 0.603; 0.279; 0.448 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients |
-0.04; -0.20; -0.09; -0.06; -0.25; -0.12 | — |
| SECONDARY Change From Baseline in Asthma Control Questionnaire (ACQ) as a Measure of Asthma Control in Overall Patients, Adolescents Only (SIROCCO/CALIMA) |
0.26; 0.06; 0.16; -0.14; -0.10; -0.12 | — |
| SECONDARY Change From Baseline in Total Score of Asthma Related and General Health-related Quality of Life Questionnaire (AQLQ(S)+12) |
0.02; 0.21; 0.08; 0.08; 0.26; 0.15 | — |
| SECONDARY Change From Baseline in Total Score of Asthma Related and General Health-related Quality of Life Questionnaire (AQLQ(S)+12), Adolescents Only (SIROCCO/CALIMA) |
0.60; -0.11; 0.25; 0.52; 0.06; 0.29 | — |
| SECONDARY Change of Blood Eosinophil Levels' Measurement in Overall Patients |
4.9; -449.6; -148.6; -10.1; -422.5; -154.1 | — |
| SECONDARY Change of Blood Eosinophil Levels' Measurement in Adolescents Patients (SIROCCO/CALIMA). |
78.3; -356.7; -139.2; -163.6; -332.9; -229.4 | — |
| SECONDARY Change From Baseline in EQ-5D-5L Visual Analog Scale |
6.08; 6.02; 4.38; 6.69; 5.00; 1.36 | — |
| SECONDARY Change From Baseline in EQ-5D-5L Visual Analog Scale, Adolescents Only (SIROCCO/CALIMA) |
5.43; 6.63; 6.07; 11.54; 9.83; 10.72 | — |
| SECONDARY Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI) |
23.3; 21.0; 32.7; 25.8; 18.9; 21.0 | — |
| SECONDARY Work Productivity Loss in Adults, Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA) |
0.0; 10.0; 3; 20.0; 10.0; 15.0 | — |
| SECONDARY Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ) |
3.8; 15.2; 5.0; 17.1 | — |
| SECONDARY Classroom Productivity Loss Using Classroom Impairment Questionnaire (CIQ), Adolescents Only (SIROCCO/CALIMA) |
4.9; 15.2; 9.5; 5.4; 18.6; 12.3 | — |
| SECONDARY Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI) |
26.6; 24.4; 33.6; 32.7; 28.4; 39.0 | — |
| SECONDARY Activity Impairment (%), Using Work Productivity and Activity Impairment Questionnaire (WPAI), Adolescents Only (SIROCCO/CALIMA) |
7.1; 5.0; 6.0; 5.4; 19.2; 12.3 | — |
| SECONDARY 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 |
193; 198; 118; 102; 20; 25 | — |
| SECONDARY 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) |
2; 5; 7; 7; 7; 14 | — |
| SECONDARY Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study |
714.25; NA; 142.92; NA; 964.21; NA | — |
| SECONDARY Pre-dose Benralizumab Concentration in Serum During the Treatment Phase of the Safety Study, Adolescents Only (SIROCCO/CALIMA) |
725.55; NA; 218.53; NA; 383.73; 853.51 | — |
| SECONDARY Number of Patients With Anti-drug Antibodies (ADA) Responses During the Study |
80; 93; 4; 8; 23; 41 | — |
| SECONDARY Number of Patients With Anti-drug Antibodies (ADA) Responses During the Study, Adolescents Only (SIROCCO/CALIMA) |
1; 5; 0; 3; 0; 2 | — |
Eligibility Criteria
Inclusion criteria
- 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 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, 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
Data sourced from ClinicalTrials.gov (NCT02258542) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.