Efficacy and Safety Study of Benralizumab in Adults and Adolescents Inadequately Controlled on Inhaled Corticosteroid Plus Long-acting β2 Agonist
A Multicentre, Randomized, Double-blind, Parallel Group, Placebocontrolled, Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab in Asthmatic Adults and Adolescents Inadequately Controlled on Inhaled Corticosteroid Plus Long-acting β2 Agonist (CALIMA)
1 other identifier
interventional
2,508
11 countries
215
Brief Summary
The purpose of this study is to determine whether Benralizumab reduces the exacerbation rate in patients with a history of asthma exacerbations and uncontrolled asthma receiving ICS-LABA with or without oral corticosteroids and additional asthma controllers.
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 Aug 2013
Typical duration for phase_3 asthma
215 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
July 31, 2013
CompletedStudy Start
First participant enrolled
August 1, 2013
CompletedFirst Posted
Study publicly available on registry
August 2, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2016
CompletedResults Posted
Study results publicly available
January 25, 2017
CompletedJanuary 25, 2017
November 1, 2016
2.6 years
July 31, 2013
September 8, 2016
November 30, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline 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 56.
Secondary Outcomes (22)
Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL
Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils >=300/uL
Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline Eosinophils <300/uL
Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils >=300/uL
Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 Asthma Symptoms Score for Patients With Baseline Eosinophils <300/uL
Immediately following the first administration of study drug through Study Week 56.
- +17 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 52 inclusive.
Eligibility Criteria
You may qualify if:
- Provision of informed consent prior to any study specific procedures
- Female and male aged 12 to 75 years, inclusively, at the time of Visit 1
- 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. The ICS and LABA can be parts of a combination product or given by separate inhalers. The ICS dose must be greater than or equal to 500 μg/day fluticasone propionate dry powder formulation or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion.
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 (215)
Research Site
Andalusia, Alabama, United States
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Birmingham, Alabama, United States
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Flagstaff, Arizona, United States
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Glendale, Arizona, United States
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Phoenix, Arizona, United States
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Tucson, Arizona, United States
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Alhambra, California, United States
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Anaheim, California, United States
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Beverly Hills, California, United States
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Garden Grove, California, United States
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Lakewood, California, United States
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North Hollywood, California, United States
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Northridge, California, United States
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Palmdale, California, United States
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Rancho Mirage, California, United States
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Redondo Beach, California, United States
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Rolling Hills Estate, California, United States
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Sacramento, California, United States
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Stockton, California, United States
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Thousand Oaks, California, United States
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Upland, California, United States
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Ventura, California, United States
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Walnut Creek, California, United States
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Westminster, California, United States
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Woodland, California, United States
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Centennial, Colorado, United States
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Colorado Springs, Colorado, United States
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Wheat Ridge, Colorado, United States
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Celebration, Florida, United States
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Fort Lauderdale, Florida, United States
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Hialeah, Florida, United States
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Homestead, Florida, United States
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Jacksonville, Florida, United States
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Lehigh Acres, Florida, United States
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Miami, Florida, United States
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Ocala, Florida, United States
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Orlando, Florida, United States
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Ormond Beach, Florida, United States
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Virginia Gardens, Florida, United States
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Gainesville, Georgia, United States
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Smyrna, Georgia, United States
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Eagle, Idaho, United States
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Shiloh, Illinois, United States
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Lenexa, Kansas, United States
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Fort Mitchell, Kentucky, United States
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Covington, Louisiana, United States
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Bangor, Maine, United States
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Farmington Hills, Michigan, United States
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Flint, Michigan, United States
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Traverse City, Michigan, United States
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Minneapolis, Minnesota, United States
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St Louis, Missouri, United States
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Las Vagas, Nevada, United States
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Union, New Jersey, United States
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The Bronx, New York, United States
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Durham, North Carolina, United States
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Wilmington, North Carolina, United States
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Cincinnati, Ohio, United States
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Columbus, Ohio, United States
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Dayton, Ohio, United States
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Middleburg Heights, Ohio, United States
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Oklahoma City, Oklahoma, United States
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Corvallis, Oregon, United States
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Portland, Oregon, United States
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Jefferson Hills, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Old Point Station, South Carolina, United States
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Rapid City, South Dakota, United States
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Knoxville, Tennessee, United States
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Arlington, Texas, United States
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Austin, Texas, United States
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Boerne, Texas, United States
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Dallas, Texas, United States
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Houston, Texas, United States
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San Antonio, Texas, United States
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Midvale, Utah, United States
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Murray, Utah, United States
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Fairfax, Virginia, United States
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Falls Church, Virginia, United States
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Madison, Wisconsin, United States
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Milwaukee, Wisconsin, United States
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Buenos Aires, Argentina
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Caba, Argentina
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Ciudad Autónoma de Bs. As., Argentina
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Ciudad de Buenos Aires, Argentina
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Concepción del Uruguay, Argentina
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Corrientes, Argentina
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Córdoba, Argentina
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Florida, Argentina
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Godoy Cruz, Argentina
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La Plata, Argentina
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Mar del Plata, Argentina
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Mendoza, Argentina
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Ranelagh, Argentina
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Rosario, Argentina
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San Miguel de Tucumán, Argentina
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Calgary, Alberta, Canada
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Sherwood Park, Alberta, Canada
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Vancouver, British Columbia, Canada
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Moncton, New Brunswick, Canada
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Burlington, Ontario, Canada
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Hamilton, Ontario, Canada
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Ottawa, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Saint-Charles-Borromée, Quebec, Canada
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Concepción, Chile
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Quillota, Chile
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Santiago, Chile
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Talcahuano, Chile
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Valparaíso, Chile
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Viña del Mar, Chile
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Aschaffenburg, Germany
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Bamberg, Germany
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Berlin, Germany
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Bonn, Germany
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Frankfurt, Germany
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Frankfurt am Main, Germany
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Geesthacht, Germany
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Gelsenkirchen, Germany
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Hamburg, Germany
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Hanover, Germany
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Herford, Germany
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Leipzig, Germany
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Mainz, Germany
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München, Germany
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Neu-Isenburg, Germany
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Rostock, Germany
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Rüdersdorf, Germany
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Witten, Germany
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Asahi-shi, Japan
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Chiyoda-ku, Japan
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Chūōku, Japan
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Fukuoka, Japan
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Himeji-shi, Japan
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Hiroshima, Japan
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Itabashi-ku, Japan
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Kagoshima, Japan
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Kishiwada-shi, Japan
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Kobe, Japan
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Kokubunji-shi, Japan
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Matsue, Japan
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Minatoku, Japan
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Mizunami-shi, Japan
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Niigata, Japan
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Obihiro-shi, Japan
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Ota-shi, Japan
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Ōita, Japan
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Sagamihara-shi, Japan
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Sakaide-shi, Japan
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Sakaishi, Japan
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Sapporo, Japan
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Sendai, Japan
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Setagaya-ku, Japan
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Shibuya-ku, Japan
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Shinagawa-ku, Japan
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Sumida-ku, Japan
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Takamatsu, Japan
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Toshima-ku, Japan
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Tsukubo-gun, Japan
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Yokohama, Japan
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Iloilo City, Philippines
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Lipa City, Philippines
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Quezon City, Philippines
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Aleksandrów Łódzki, Poland
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Bialystok, Poland
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Bielsko-Biala, Poland
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Bydgoszcz, Poland
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Bystra, Poland
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Gdansk, Poland
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Gorzów Wlkp, Poland
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Karczew, Poland
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Katowice, Poland
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Koszalin, Poland
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Krakow, Poland
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Lodz, Poland
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Lubin, Poland
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Lublin, Poland
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Ostrów Wielkopolski, Poland
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Poznan, Poland
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Ruda Śląska, Poland
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Rzeszów, Poland
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Skierniewice, Poland
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Szczecin, Poland
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Tarnów, Poland
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Torun, Poland
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Trzebnica, Poland
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Warsaw, Poland
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Wieluń, Poland
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Wroclaw, Poland
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Zabrze, Poland
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Żnin, Poland
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Łęczna, Poland
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Bragadiru, Romania
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Brasov, Romania
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Bucharest, Romania
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Constanța, Romania
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Deva, Romania
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Iași, Romania
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Timișoara, Romania
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Gothenburg, Sweden
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Luleå, Sweden
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Lund, Sweden
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Chernivtsi, Ukraine
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Dnipropetrovsk, Ukraine
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Ivano-Frankivsk, Ukraine
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Kharkiv, Ukraine
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Kyiv, Ukraine
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Lutsk, Ukraine
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Mykolayiv, Ukraine
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Uzhhorod, Ukraine
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Vinnytsia, Ukraine
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Zaporizhzhia, Ukraine
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Zaporizhzhya, Ukraine
Related Publications (10)
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: 29409951DERIVEDOhta K, Adachi M, Tohda Y, Kamei T, Kato M, Mark Fitzgerald J, Takanuma M, Kakuno T, Imai N, Wu Y, Aurivillius M, Goldman M. Efficacy and safety of benralizumab in Japanese patients with severe, uncontrolled eosinophilic asthma. Allergol Int. 2018 Apr;67(2):266-272. doi: 10.1016/j.alit.2017.10.004. Epub 2017 Nov 8.
PMID: 29128192DERIVEDFitzGerald JM, Bleecker ER, Nair P, Korn S, Ohta K, Lommatzsch M, Ferguson GT, Busse WW, Barker P, Sproule S, Gilmartin G, Werkstrom V, Aurivillius M, Goldman M; CALIMA study investigators. Benralizumab, an anti-interleukin-5 receptor alpha monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016 Oct 29;388(10056):2128-2141. doi: 10.1016/S0140-6736(16)31322-8. Epub 2016 Sep 5.
PMID: 27609406DERIVED
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
Mark Fitzgerald, MD, PhD, Professor of Medicine
The Lung Centre, Gordon and Leslie Diamond Health Care Centre, Vancouver Canada
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
July 31, 2013
First Posted
August 2, 2013
Study Start
August 1, 2013
Primary Completion
March 1, 2016
Study Completion
March 1, 2016
Last Updated
January 25, 2017
Results First Posted
January 25, 2017
Record last verified: 2016-11