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

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

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).

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Biological: Benralizumab; Biological: Benralizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 447
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1414AIF
    • Research Site
  • Ciudad de Buenos Aire, Argentina, C1121 ABE
    • Research Site
  • La Plata, Argentina, B1902COS
    • Research Site
  • Mendoza, Argentina, 5500
    • Research Site
  • Mendoza, Argentina, M5500GIP
    • Research Site
• Australia
  • Frankston, Australia, 3199
    • Research Site
  • Nedlands, Australia, 6009
    • Research Site
  • Parkville, Australia, 3050
    • Research Site
  • Randwick, Australia, 2031
    • Research Site
  • Woolloongabba, Australia, 4102
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• Bulgaria
  • Pazardzhik, Bulgaria, 4400
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  • Pernik, Bulgaria, 2300
    • Research Site
  • Petrich, Bulgaria, 2850
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  • Ruse, Bulgaria, 7002
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  • Sliven, Bulgaria, 8800
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  • Vratsa, Bulgaria, 3000
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• Canada
  • Quebec, Canada, G1G 3Y8
    • Research Site
  • Quebec, Canada, G1V 4G5
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  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Research Site
    • Sherwood Park, Alberta, Canada, T8L 0N2
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Research Site
    • Ottawa, Ontario, Canada, K1G 6C6
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  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
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    • Montreal, Quebec, Canada, H2W 1T8
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• Chile
  • Quillota, Chile, 2260000
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  • Talcahuano, Chile, 4270918
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  • Valparaiso, Chile, 2341131
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• Czechia
  • Karlovy Vary, Czechia, 360 17
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  • Plzen, Czechia, 304 60
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  • Praha, Czechia, 130 00
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  • Rokycany, Czechia, 337 22
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• France
  • Brest Cedex 2, France, 29609
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  • Dijon Cedex, France, 21079
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  • Le Kremlin Bicêtre, France, 94275
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  • Le Mans Cedex, France, 72037
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  • Lyon Cedex 04, France, 69317
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  • Marseille Cedex 20, France, 13915
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  • Montpellier, France, 34295
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  • Paris, France, 75018
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  • Pringy Cedex, France, 74374
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  • Saint Pierre, France, 97448
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  • Strasbourg Cedex, France, 67091
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  • Toulouse Cedex 9, France, 31059
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• Germany
  • Aschaffenburg, Germany, 63739
    • Research Site
  • Bamberg, Germany, 96049
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  • Berlin, Germany, 10367
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  • Frankfurt, Germany, 60596
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  • Frankfurt/Main, Germany, 60389
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  • Geesthacht, Germany, 21502
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  • Grosshansdorf, Germany, 20927
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  • Hamburg, Germany, 22299
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  • Hannover, Germany, D-30173
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  • Leipzig, Germany, 04103
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  • Leipzig, Germany, 04207
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  • Mainz, Germany, 55131
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  • Marburg, Germany, 30625
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  • Rüdersdorf, Germany, 15562
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• Poland
  • Aleksandrów Łódzki, Poland, 95-070
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  • Białystok, Poland, 15-430
    • Research Site
  • Bydgoszcz, Poland, 85-168
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  • Dobre Miasto, Poland, 11-040
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  • Gdańsk, Poland, 80-214
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  • Gorzów Wlkp, Poland, 66-400
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  • Grodzisk Mazowiecki, Poland, 05-825
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  • Kościan, Poland, 64-000
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  • Kraków, Poland, 31-011
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  • Kraków, Poland, 31-033
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  • Lubin, Poland, 59-300
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  • Lublin, Poland, 20-552
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  • Ostrów Wielkopolski, Poland, 63-400
    • Research Site
  • Poznań, Poland, 60-685
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  • Poznań, Poland, 60-693
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  • Poznań, Poland, 60-823
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  • Proszowice, Poland, 32-100
    • Research Site
  • Ruda Slaska, Poland, 41-709
    • Research Site
  • Rzeszów, Poland, 35-205
    • Research Site
  • Skierniewice, Poland, 96-100
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  • Sosnowiec, Poland, 41-200
    • Research Site
  • Tarnów, Poland, 33-100
    • Research Site
  • Trzebnica, Poland, 55-100
    • Research Site
  • Warszawa, Poland, 01-138
    • Research Site
  • Warszawa, Poland, 01-868
    • Research Site
  • Wieluń, Poland, 98-300
    • Research Site
  • Wołomin, Poland, 05-200
    • Research Site
  • Wrocław, Poland, 53-301
    • Research Site
  • Wrocław, Poland, 50-220
    • Research Site
  • Wrocław, Poland, 51-162
    • Research Site
  • Łódź, Poland, 90-141
    • Research Site
  • Łódź, Poland, 91-103
    • Research Site
  • Żnin, Poland, 88-400
    • Research Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620039
    • Research Site
  • Nizhny Novgorod, Russian Federation, 603126
    • Research Site
  • Saratov, Russian Federation, 410053
    • Research Site
  • Smolensk, Russian Federation, 214019
    • Research Site
  • St. Petersburg, Russian Federation, 196247
    • Research Site
  • Vladikavkaz, Russian Federation, 362007
    • Research Site
  • Volgograd, Russian Federation, 400001
    • Research Site
  • Volgograd, Russian Federation, 400131
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  • Yekaterinburg, Russian Federation, 620149
    • Research Site
• Spain
  • Málaga, Spain, 29010
    • Research Site
  • Palma de Mallorca, Spain, 07010
    • Research Site
  • Sagunto(Valencia), Spain, 46520
    • Research Site
  • Salamanca, Spain, 37007
    • Research Site
  • Valencia, Spain, 46017
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  • Valencia, Spain, 46015
    • Research Site
• Turkey
  • Adana, Turkey, 01330
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  • Ankara, Turkey, 06230
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  • Bursa, Turkey, 16059
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  • Istanbul, Turkey, 34098
    • Research Site
• Ukraine
  • Dnipro, Ukraine, 49006
    • Research Site
  • Ivano-Frankivsk, Ukraine, 76018
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  • Kharkiv Region, Ukraine, 61039
    • Research Site
  • Kharkiv Region, Ukraine, 61022
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  • Kharkiv Region, Ukraine, 61035
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  • Kharkiv Region, Ukraine, 61058
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  • Kyiv, Ukraine, 03680
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  • Kyiv, Ukraine, 04201
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  • Lutsk, Ukraine, 4300
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  • Vinnytsia, Ukraine, 21029
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • Research Site
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Chertsey, United Kingdom, B9 5SS
    • Research Site
  • Cottingham, United Kingdom, HU16 5JQ
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
  • Stevenage, United Kingdom, SG1 4AB
    • Research Site
• United States
  • Alabama
    • Scottsboro, Alabama, United States, 35768
      • Research Site
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Research Site
    • Phoenix, Arizona, United States, 85012
      • Research Site
  • California
    • Bakersfield, California, United States, 93301
      • Research Site
    • Newport Beach, California, United States, 92663
      • Research Site
    • Redondo Beach, California, United States, 90277
      • Research Site
    • Roseville, California, United States, 95661
      • Research Site
    • Sacramento, California, United States, 95825
      • Research Site
    • San Jose, California, United States, 95117
      • Research Site
    • Stockton, California, United States, 95204
      • Research Site
    • Westminster, California, United States, 92683
      • Research Site
    • Woodland, California, United States, 95695
      • Research Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Research Site
    • Denver, Colorado, United States, 80206
      • Research Site
    • Wheat Ridge, Colorado, United States, 80033
      • Research Site
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Research Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • Research Site
    • Doral, Florida, United States, 33172
      • Research Site
    • Hialeah, Florida, United States, 33012
      • Research Site
    • Miami, Florida, United States, 33176
      • Research Site
    • Miami, Florida, United States, 33134
      • Research Site
    • Miami, Florida, United States, 33144
      • Research Site
    • Orlando, Florida, United States, 32825
      • Research Site
    • Orlando, Florida, United States, 32819
      • Research Site
    • Winter Park, Florida, United States, 32789
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Research Site
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
      • Research Site
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Research Site
    • Flint, Michigan, United States, 48504
      • Research Site
    • Traverse City, Michigan, United States, 49686
      • Research Site
  • New York
    • Bronx, New York, United States, 10461
      • Research Site
    • New York, New York, United States, 10016
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Research Site
    • Winston-Salem, North Carolina, United States, 27103
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • Research Site
    • Middleburg Heights, Ohio, United States, 44130
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Research Site
    • Oklahoma City, Oklahoma, United States, 73103
      • Research Site
  • Pennsylvania
    • Jefferson Hills, Pennsylvania, United States, 15025
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19140
      • Research Site
  • South Carolina
    • Hodges, South Carolina, United States, 29653
      • Research Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Research Site
  • Texas
    • Dallas, Texas, United States, 75225
      • Research Site
    • Dallas, Texas, United States, 75235
      • Research Site
    • Houston, Texas, United States, 77058
      • Research Site
    • Houston, Texas, United States, 77081
      • Research Site
    • Houston, Texas, United States, 77083
      • Research Site
    • McKinney, Texas, United States, 75069
      • Research Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • Research Site
    • Falls Church, Virginia, United States, 22044
      • Research Site
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 126 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Benralizumab Arm A; Benralizumab administered subcutaneously every 4 weeks	Biological: Benralizumab; Benralizumab administered subcutaneously every 4 weeks; Biological: Benralizumab; Benralizumab administered subcutaneously every 8 weeks
Other: Benralizumab Arm B; Benralizumab administered subcutaneously every 8 weeks	Biological: Benralizumab; Benralizumab administered subcutaneously every 4 weeks; Biological: Benralizumab; Benralizumab administered subcutaneously every 8 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• CSP redacted.
• SAP redacted.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2016
• Primary Completion (Actual): June 18, 2020
• Study Completion (Actual): June 18, 2020

Study Registration Dates

• First Submitted: June 7, 2016
• First Submitted That Met QC Criteria: June 17, 2016
• First Posted (Estimate): June 22, 2016

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Asthma; Bronchial Diseases; Respiratory Tract Diseases; Obstructive Lung Diseases; Lung Diseases
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3250C00037

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)