Efficacy and Safety Study of Benralizumab Added to High-dose Inhaled Corticosteroid Plus LABA in Patients With Uncontrolled Asthma
A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled, Phase III Efficacy and Safety Study of Benralizumab (MEDI-563) Added to High-dose Inhaled Corticosteroid Plus Long-acting β2 Agonist in Patients With Uncontrolled Asthma
1 other identifier
interventional
2,681
17 countries
275
Brief Summary
The purpose of this study is to determine whether Benralizumab reduces the number of asthma exacerbations in patients who remain uncontrolled on high doses of ICS-LABA.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 asthma
Started Sep 2013
Typical duration for phase_3 asthma
275 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 16, 2013
CompletedFirst Posted
Study publicly available on registry
August 27, 2013
CompletedStudy Start
First participant enrolled
September 19, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 5, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
April 5, 2016
CompletedResults Posted
Study results publicly available
May 3, 2017
CompletedMay 3, 2017
March 1, 2017
2.5 years
August 16, 2013
September 28, 2016
March 23, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils >=300/uL
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF
Immediately following the first administration of study drug through Study Week 48.
Secondary Outcomes (23)
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Eosinophils < 300/uL
Immediately following the first administration of study drug through Study Week 48.
Annual Asthma Exacerbation Rate Resulting Emergency Room Visits and Hospitalizations
Immediately following the first administration of study drug through Study Week 48.
Number of Patients With >=1 Asthma Exacerbations
Immediately following the first administration of study drug through Study Week 48.
Time to First Asthma Exacerbation
Immediately following the first administration of study drug through Study Week 48.
Mean Change From Baseline to Week 48 in Pre-bronchodilator FEV1 (L) Value for Baseline Eosinophils >=300/uL
Immediately following the first administration of study drug through Study Week 48.
- +18 more secondary outcomes
Study Arms (3)
Benralizumab 30 mg q.4 weeks
EXPERIMENTALBenralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks
EXPERIMENTALBenralizumab administered subcutaneously every 8 weeks
Placebo
PLACEBO COMPARATORPlacebo administered subcutaneously
Interventions
Benralizumab subcutaneously on study week 0 until study week 44 inclusive.
Eligibility Criteria
You may qualify if:
- Written informed consent 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 aged 12 to 75 years inclusively, at the time of visit 1. For those patients, who are 17 on the day of Visit 1 but will turn 18 after this day, will be considered an adolescent for the purposes of this trial.
- History of physician-diagnosed asthma requiring treatment with medium-to-high dose ICS (\>250μg fluticasone dry powder formulation equivalents total daily dose) and a LABA, for at least 12 months prior to Visit 1
- Documented treatment with ICS and LABA for at least 3 months prior to Visit 1 with or without oral corticosteroids and additional asthma controllers.
- For subjects 18 years of age and older, the ICS dose must be \>500 mcg/day fluticasone propionate dry powder formulation or equivalent daily.
- For subjects ages 12-17, the ICS dose must be ≥500 mcg /day fluticasone propionate dry powder formulation or equivalent daily.
You may not qualify if:
- Clinically important pulmonary disease other than asthma (e.g. active lung infection, COPD, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg- Strauss syndrome, hypereosinophilic syndrome)
- 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
- Acute upper or lower respiratory infections requiring antibiotics or antiviral medication within 30 days prior to the date informed consent is obtained or during the screening/run-in period
- Any clinically significant abnormal findings in physical examination, vital signs, haematology, clinical chemistry, or urinalysis during screening/run-in period, 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 the patient's ability to complete entire duration of the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (275)
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Foley, Alabama, United States
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Huntsville, Alabama, United States
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Mobile, Alabama, United States
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Scottsboro, Alabama, United States
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Sheffield, Alabama, United States
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Phoenix, Arizona, United States
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Tucson, Arizona, United States
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Bakersfield, California, United States
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Beverly Hills, California, United States
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Costa Mesa, California, United States
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Huntington Beach, California, United States
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Huntington Park, California, United States
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Los Angles, California, United States
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Newport Beach, California, United States
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Orange, California, United States
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Riverside, California, United States
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San Jose, California, United States
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Santa Ana, California, United States
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Hartford, Connecticut, United States
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New Haven, Connecticut, United States
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Brandon, Florida, United States
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Clearwater, Florida, United States
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Cutler Bay, Florida, United States
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DeLand, Florida, United States
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Gainesville, Florida, United States
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Hialeah, Florida, United States
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Hollywood, Florida, United States
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Homestead, Florida, United States
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Jackonsville, Florida, United States
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Lynn Haven, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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Pembroke Pines, Florida, United States
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Port Charlotte, Florida, United States
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Sebring, Florida, United States
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St. Petersburg, Florida, United States
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Tampa, Florida, United States
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Vero Beach, Florida, United States
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Winter Park, Florida, United States
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Albany, Georgia, United States
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Gainesville, Georgia, United States
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Lawrenceville, Georgia, United States
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Gurnee, Illinois, United States
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Normal, Illinois, United States
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Iowa City, Iowa, United States
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Fort Mitchell, Kentucky, United States
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Hazard, Kentucky, United States
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Louisville, Kentucky, United States
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Opelousas, Louisiana, United States
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Baltimore, Maryland, United States
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Gardner, Massachusetts, United States
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North Dartmouth, Massachusetts, United States
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Quincy, Massachusetts, United States
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Farmington Hills, Michigan, United States
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Rochester, Minnesota, United States
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Saint Paul, Minnesota, United States
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Picayune, Mississippi, United States
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Billings, Montana, United States
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Bellevue, Nebraska, United States
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Las Vegas, Nevada, United States
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Sparks, Nevada, United States
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Marlton, New Jersey, United States
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Northfield, New Jersey, United States
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Union, New Jersey, United States
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Albuquerque, New Mexico, United States
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Hopewell Jct, New York, United States
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New York, New York, United States
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Staten Island, New York, United States
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The Bronx, New York, United States
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Huntersville, North Carolina, United States
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Shelby, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Grand Forks, North Dakota, United States
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Oregon, Ohio, United States
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Toledo, Ohio, United States
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Wooster, Ohio, United States
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Oklahoma City, Oklahoma, United States
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Tulsa, Oklahoma, United States
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Erie, Pennsylvania, United States
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Feasterville, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Phoenixville, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Warwick, Rhode Island, United States
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Charleston, South Carolina, United States
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Easley, South Carolina, United States
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Hodges, South Carolina, United States
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Mt. Pleasant, South Carolina, United States
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Rock Hill, South Carolina, United States
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Chattanooga, Tennessee, United States
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Germantown, Tennessee, United States
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Allen, Texas, United States
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Dallas, Texas, United States
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Dickinson, Texas, United States
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Duncanville, Texas, United States
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Georgetown, Texas, United States
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Houston, Texas, United States
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McAllen, Texas, United States
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McKinney, Texas, United States
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Pharr, Texas, United States
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Plano, Texas, United States
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Sealy, Texas, United States
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Splendora, Texas, United States
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Orem, Utah, United States
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Provo, Utah, United States
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Salt Lake City, Utah, United States
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Abingdon, Virginia, United States
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Hopewell, Virginia, United States
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Morgantown, West Virginia, United States
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Greenfield, Wisconsin, United States
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Bedford Park, Australia
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Box Hill, Australia
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Clayton, Australia
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Concord, Australia
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Frankston, Australia
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Nedlands, Australia
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New Lambton Heights, Australia
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Parkville, Australia
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Prahran, Australia
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Randwick, Australia
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Woolloongabba, Australia
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Porto Alegre, Brazil
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Rio de Janeiro, Brazil
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Santo André, Brazil
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São Paulo, Brazil
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Sorocaba, Brazil
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Dupnitsa, Bulgaria
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Pernik, Bulgaria
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Pleven, Bulgaria
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Rousse, Bulgaria
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Samokov, Bulgaria
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Sliven, Bulgaria
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Sofia, Bulgaria
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Stara Zagora, Bulgaria
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Varna, Bulgaria
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Velingrad, Bulgaria
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Yambol, Bulgaria
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Brno, Czechia
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Jindřichův Hradec, Czechia
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Karlovy Vary, Czechia
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Ostrava, Czechia
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Pardubice, Czechia
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Pilsen, Czechia
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Prague, Czechia
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Rokycany, Czechia
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Strakonice, Czechia
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Teplice, Czechia
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Brest, France
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Clermont-Ferrand, France
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Dijon, France
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Le Kremlin-Bicêtre, France
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Le Mans, France
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Lyon, France
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Marseille, France
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Montpellier, France
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Paris, France
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Pau, France
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Pringy, France
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Saint-Pierre, France
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Strasbourg, France
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Toulouse, France
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Bari, Italy
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Bologna, Italy
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Catania, Italy
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Cona, Italy
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Florence, Italy
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Foggia, Italy
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Legnago, Italy
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Milan, Italy
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Napoli, Italy
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Palermo, Italy
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Pavia, Italy
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Perugia, Italy
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Pisa, Italy
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Roma, Italy
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San Pietro Vernotico, Italy
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Torino, Italy
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Verona, Italy
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Guadalajara, Mexico
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Monterrey, Mexico
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Morelia, Mexico
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Cusco, Peru
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Lima, Peru
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Surco, Peru
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Bialystok, Poland
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Dobre Miasto, Poland
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Gdansk, Poland
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Giżycko, Poland
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Grodzisk Mazowiecki, Poland
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Kościan, Poland
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Legnica, Poland
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Lodz, Poland
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Lublin, Poland
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Poznan, Poland
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Proszowice, Poland
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Rzeszów, Poland
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Sosnowiec, Poland
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Wołomin, Poland
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Wroclaw, Poland
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Zgierz, Poland
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Chelyabinsk, Russia
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Ivanovo, Russia
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Izhevsk, Russia
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Kazan', Russia
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Moscow, Russia
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Nizhny Novgorod, Russia
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Novosibirsk, Russia
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Pyatigorsk, Russia
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Rostov-on-Don, Russia
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Ryazan, Russia
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Saint Petersburg, Russia
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Saratov, Russia
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Smolensk, Russia
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StPetersburg, Russia
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Tomsk, Russia
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Vladikavkaz, Russia
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Vladimir, Russia
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Volgograd, Russia
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Yaroslavl, Russia
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Yekaterinburg, Russia
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Benoni, South Africa
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Cape Town, South Africa
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Durban, South Africa
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KwaDukuza, South Africa
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Mowbray, South Africa
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Anyang-si, South Korea
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Bucheon-si, South Korea
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Busan, South Korea
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Cheongju-si, South Korea
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Gwangju, South Korea
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Incheon, South Korea
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Jeju City, South Korea
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Seoul, South Korea
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Suwon, South Korea
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Barcelona, Spain
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Lugo, Spain
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Madrid, Spain
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Málaga, Spain
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Oviedo, Spain
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Palma de Mallorca, Spain
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Sagunto(Valencia), Spain
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Salamanca, Spain
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Valencia, Spain
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Adana, Turkey (Türkiye)
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Ankara, Turkey (Türkiye)
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Antalya, Turkey (Türkiye)
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Bursa, Turkey (Türkiye)
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Istanbul, Turkey (Türkiye)
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Izmir, Turkey (Türkiye)
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Kocaeli, Turkey (Türkiye)
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Mersin, Turkey (Türkiye)
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Birmingham, United Kingdom
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Bradford, United Kingdom
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Cambridge, United Kingdom
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Chertsey, United Kingdom
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Chester, United Kingdom
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Chippenham, United Kingdom
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Cottingham, United Kingdom
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Darlington, United Kingdom
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Glasgow, United Kingdom
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High Heaton/Newcastle Upon Tyn, United Kingdom
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Leeds, United Kingdom
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Liverpool, United Kingdom
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London, United Kingdom
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Maidstone, United Kingdom
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Manchester, United Kingdom
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Nottingham, United Kingdom
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Plymouth, United Kingdom
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Portsmouth, United Kingdom
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Soham, United Kingdom
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Somerset, United Kingdom
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Stevenage, United Kingdom
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Stockton, United Kingdom
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Hanoi, Vietnam
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Ho Chi Minh City, Vietnam
Related Publications (9)
Menzies-Gow A, Hoyte FL, Price DB, Cohen D, Barker P, Kreindler J, Jison M, Brooks CL, Papeleu P, Katial R. Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab. Adv Ther. 2022 May;39(5):2065-2084. doi: 10.1007/s12325-022-02098-1. Epub 2022 Mar 14.
PMID: 35287231DERIVEDLugogo NL, Kreindler JL, Martin UJ, Cook B, Hirsch I, Trudo FJ. Blood eosinophil count group shifts and kinetics in severe eosinophilic asthma. Ann Allergy Asthma Immunol. 2020 Aug;125(2):171-176. doi: 10.1016/j.anai.2020.04.011. Epub 2020 Apr 22.
PMID: 32334141DERIVEDJackson DJ, Humbert M, Hirsch I, Newbold P, Garcia Gil E. Ability of Serum IgE Concentration to Predict Exacerbation Risk and Benralizumab Efficacy for Patients with Severe Eosinophilic Asthma. Adv Ther. 2020 Feb;37(2):718-729. doi: 10.1007/s12325-019-01191-2. Epub 2019 Dec 14.
PMID: 31836949DERIVEDChipps BE, Hirsch I, Trudo F, Alacqua M, Zangrilli JG. Benralizumab efficacy for patients with fixed airflow obstruction and severe, uncontrolled eosinophilic asthma. Ann Allergy Asthma Immunol. 2020 Jan;124(1):79-86. doi: 10.1016/j.anai.2019.10.006. Epub 2019 Oct 15.
PMID: 31626906DERIVEDChupp G, Lugogo NL, Kline JN, Ferguson GT, Hirsch I, Goldman M, Zangrilli JG, Trudo F. Rapid onset of effect of benralizumab on morning peak expiratory flow in severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2019 May;122(5):478-485. doi: 10.1016/j.anai.2019.02.016. Epub 2019 Feb 23.
PMID: 30802500DERIVEDBleecker ER, Wechsler ME, FitzGerald JM, Menzies-Gow A, Wu Y, Hirsch I, Goldman M, Newbold P, Zangrilli JG. Baseline patient factors impact on the clinical efficacy of benralizumab for severe asthma. Eur Respir J. 2018 Oct 18;52(4):1800936. doi: 10.1183/13993003.00936-2018. Print 2018 Oct.
PMID: 30139780DERIVEDDuBuske L, Newbold P, Wu Y, Trudo F. Seasonal variability of exacerbations of severe, uncontrolled eosinophilic asthma and clinical benefits of benralizumab. Allergy Asthma Proc. 2018 Sep 4;39(5):345-349. doi: 10.2500/aap.2018.39.4162. Epub 2018 Aug 4.
PMID: 30077185DERIVEDChipps BE, Newbold P, Hirsch I, Trudo F, Goldman M. Benralizumab efficacy by atopy status and serum immunoglobulin E for patients with severe, uncontrolled asthma. Ann Allergy Asthma Immunol. 2018 May;120(5):504-511.e4. doi: 10.1016/j.anai.2018.01.030. Epub 2018 Feb 1.
PMID: 29409951DERIVEDBleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, Sproule S, Gilmartin G, Aurivillius M, Werkstrom V, Goldman M; SIROCCO study investigators. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting beta2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2115-2127. doi: 10.1016/S0140-6736(16)31324-1. Epub 2016 Sep 5.
PMID: 27609408DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Mitchell Goldman , Medical Science Director
- Organization
- AstraZeneca
Study Officials
- PRINCIPAL INVESTIGATOR
Eugene R. Bleecker, MD, Professor of Medicine
Center for Genomics and Personalized Medicine Research, Medical Center Boulevard, Winston-Salem, North Carolina 27157
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 16, 2013
First Posted
August 27, 2013
Study Start
September 19, 2013
Primary Completion
April 5, 2016
Study Completion
April 5, 2016
Last Updated
May 3, 2017
Results First Posted
May 3, 2017
Record last verified: 2017-03