AsthmaPhase 3NCT01914757

Efficacy and Safety Study of Benralizumab in Adults and Adolescents Inadequately Controlled on Inhaled Corticosteroid Plus Long-acting β2 Agonist

A Phase 3 study testing Benralizumab in people with Asthma, run by AstraZeneca at 214 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial 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. Read more about this study

Who is it for?: Ages 12 to 75 years
Conditions the study is for: Asthma
What is being tested?: Benralizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 2,508 participants
Where: 214 sitesin 11 countries
Study dates: Aug 2013to Mar 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 12 to 75 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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.

Who cannot join

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

Trial locations and contacts

214 sites in 11 countries.

Country

City, postcode or hospital

214 sites in 11 countries

United States81 sites

Research Site
Alhambra, California
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Anaheim, California
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Andalusia, Alabama
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Arlington, Texas
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Austin, Texas
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Bangor, Maine
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Beverly Hills, California
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Birmingham, Alabama
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Boerne, Texas
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Celebration, Florida
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Centennial, Colorado
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Cincinnati, Ohio
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Colorado Springs, Colorado
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Columbus, Ohio
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Corvallis, Oregon
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Covington, Louisiana
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Dallas, Texas
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Dayton, Ohio
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Durham, North Carolina
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Eagle, Idaho
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Fairfax, Virginia
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Falls Church, Virginia
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Farmington Hills, Michigan
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Flagstaff, Arizona
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Flint, Michigan
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Fort Lauderdale, Florida
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Fort Mitchell, Kentucky
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Gainesville, Georgia
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Garden Grove, California
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Glendale, Arizona
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Hialeah, Florida
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Homestead, Florida
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Houston, Texas
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Jacksonville, Florida
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Jefferson Hills, Pennsylvania
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Knoxville, Tennessee
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Lakewood, California
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Las Vagas, Nevada
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Lehigh Acres, Florida
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Lenexa, Kansas
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Madison, Wisconsin
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Miami, Florida
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Middleburg Heights, Ohio
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Midvale, Utah
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Milwaukee, Wisconsin
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Minneapolis, Minnesota
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Murray, Utah
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North Hollywood, California
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Northridge, California
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Ocala, Florida
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Oklahoma City, Oklahoma
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Old Point Station, South Carolina
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Orlando, Florida
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Ormond Beach, Florida
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Palmdale, California
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Phoenix, Arizona
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Pittsburgh, Pennsylvania
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Portland, Oregon
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Rancho Mirage, California
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Rapid City, South Dakota
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Redondo Beach, California
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Rolling Hills Estate, California
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Sacramento, California
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San Antonio, Texas
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Shiloh, Illinois
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Smyrna, Georgia
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St Louis, Missouri
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Stockton, California
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The Bronx, New York
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Thousand Oaks, California
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Traverse City, Michigan
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Tucson, Arizona
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Union, New Jersey
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Upland, California
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Ventura, California
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Virginia Gardens, Florida
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Walnut Creek, California
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Westminster, California
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Wheat Ridge, Colorado
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Wilmington, North Carolina
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Woodland, California

Other trials in United States

Japan31 sites

Research Site
Asahi-shi
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Chiyoda-ku
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Chūōku
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Fukuoka
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Himeji-shi
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Hiroshima
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Kagoshima
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Kishiwada-shi
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Kobe
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Kokubunji-shi
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Matsue
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Minatoku
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Mizunami-shi
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Niigata
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Obihiro-shi
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Ōita
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Ota-shi
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Sagamihara-shi
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Sakaide-shi
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Sakaishi
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Sapporo
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Sendai
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Setagaya-ku
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Shibuya-ku
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Shinagawa-ku
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Sumida-ku
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tabashi City
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Takamatsu
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Toshima-ku
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Tsukubo-gun
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Yokohama

Other trials in Japan

Poland29 sites

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Aleksandrów Łódzki
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Bialystok
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Bielsko-Biala
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Bydgoszcz
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Bystra
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Gdansk
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Gorzów Wlkp
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Karczew
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Katowice
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Koszalin
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Krakow
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Łęczna
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Lodz
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Lubin
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Lublin
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Ostrów Wielkopolski
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Poznan
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Ruda Śląska
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Rzeszów
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Skierniewice
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Szczecin
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Tarnów
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Torun
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Trzebnica
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Warsaw
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Wieluń
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Wroclaw
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Zabrze
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Żnin

Other trials in Poland

Germany18 sites

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Aschaffenburg
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Bamberg
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Berlin
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Bonn
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Frankfurt
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Frankfurt am Main
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Geesthacht
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Gelsenkirchen
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Hamburg
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Hanover
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Herford
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Leipzig
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Mainz
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München
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Neu-Isenburg
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Rostock
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Rüdersdorf
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Witten

Other trials in Germany

Argentina15 sites

Research Site
Buenos Aires
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Caba
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Ciudad Autónoma de Bs. As.
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Ciudad de Buenos Aires
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Concepción del Uruguay
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Córdoba
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Corrientes
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Florida
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Godoy Cruz
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La Plata
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Mar del Plata
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Mendoza
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Ranelagh
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Rosario
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San Miguel de Tucumán

Other trials in Argentina

Canada11 sites

Research Site
Burlington, Ontario
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Calgary, Alberta
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Hamilton, Ontario
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Moncton, New Brunswick
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Montreal, Quebec
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Ottawa, Ontario
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Québec, Quebec
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Saint-Charles-Borromée, Quebec
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Sherwood Park, Alberta
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Toronto, Ontario
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Vancouver, British Columbia

Other trials in Canada

Ukraine10 sites

Research Site
Chernivtsi
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Dnipropetrovsk
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Ivano-Frankivsk
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Kharkiv
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Kyiv
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Lutsk
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Mykolayiv
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Uzhhorod
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Vinnytsia
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Zaporizhzhya

Other trials in Ukraine

Romania7 sites

Research Site
Bragadiru
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Brasov
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Bucharest
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Constanța
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Deva
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Iași
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Timișoara

Other trials in Romania

Chile6 sites

Research Site
Concepción
Research Site
Quillota
Research Site
Santiago
Research Site
Talcahuano
Research Site
Valparaíso
Research Site
Viña del Mar

Other trials in Chile

Philippines3 sites

Research Site
Iloilo City
Research Site
Lipa City
Research Site
Quezon City

Other trials in Philippines

Sweden3 sites

Research Site
Gothenburg
Research Site
Luleå
Research Site
Lund

Other trials in Sweden

About this study

Official title: 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)

Conditions: Asthma
Being tested: Benralizumab, Placebo
Keywords: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases
Medical subject headings: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Lung Diseases, Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BenralizumabBiological
Benralizumab subcutaneously on study week 0 until study week 52 inclusive.
PlaceboBiological
Placebo subcutaneously on study week 0 until study week 52 inclusive.

Study groups in NCT01914757
Study group	Role	What they receive
Benralizumab 30 mg q.4 weeks	Experimental	Benralizumab administered subcutaneously every 4 weeks Receives: Biological: Benralizumab
Benralizumab 30 mg q.8 weeks	Experimental	Benralizumab administered subcutaneously every 8 weeks Receives: Biological: Benralizumab
Placebo	Placebo comparator	Placebo administered subcutaneously Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.
Measured: 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
Measured: 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
Measured: 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
Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Measured: 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
Asthma symptoms during night time and daytime are recorded by the patient each morning and evening in the asthma daily diary. Symptom score values are from 0 (No asthma symptom) to 3 (unable to sleep because of asthma). Baseline is defined as the average of data collected from the evening of study day -10 to the morning of study day 1. Each timepoint is calculated as bi-weekly means based on daily diary data. If more than 50% of scores are missing in a 14 day period then this is considered as missing. Symptom score lower is better.
Measured: Immediately following the first administration of study drug through Study Week 56.
Change in Asthma Rescue Medication Use
Change from Baseline to Week 56 in number of Rescue medication use (puffs/day)
Measured: Immediately following the first administration of study drug through Study Week 56.
Home Lung Function Assessments Based on PEF
Change from Baseline to Week 56 in Home lung function (morning and evening Peak expiratory flow [PEF])
Measured: Immediately following the first administration of study drug through Study Week 56.
Proportion of Nights With Awakening Due to Asthma
Change from Baseline to Week 56 on Proportion of Nights with awakening due to asthma
Measured: Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL
ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.
Measured: Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL
ACQ-6 contains one bronchodilator question and 5 symptom questions. Questions are rated from 0 (totally controlled) to 6 (severely uncontrolled). Mean ACQ-6 score is the average of the responses. Mean scores of <=0.75 indicates well-controlled asthma, scores between 0.75 to <=1.5 indicate partly controlled asthma, and >1.5 indicates not well controlled asthma.
Measured: Immediately following the first administration of study drug through Study Week 56.
Number of Patients With >=1 Asthma Exacerbation
Measured: Immediately following the first administration of study drug through Study Week 56
Time to First Asthma Exacerbation
Measured: Immediately following the first administration of study drug through Study Week 56
Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations
Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization (adjudicated)
Measured: Immediately following the first administration of study drug through Study Week 56.
Pharmacokinetics of Benralizumab
Mean PK Concentration at each visit
Measured: Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 60
Immunogenicity of Benralizumab
Anti-drug antibodies (ADA) responses at baseline and post baseline. Persistently positive is defined as positive at >=2 post-baseline assessments (with >=16 weeks between first and last positive) or positive at last post-baseline assessment. Transiently positive is defined as having at least one post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive.
Measured: Pre-treatment until end of follow-up
Extent of Exposure
Extent of exposure is defined as the duration of treatment in days
Measured: Immediately following the first administration of study drug through Study Week 56
Mean Change From Baseline to Week 56 in AQLQ(S)+12
AQLQ(S)+12 overall score is defined as the average of all 32 questions in the AQLQ(S)+12 questionnaire. AQLQ(S)+12 is a 7-point scale questionnaire, ranging from 7 (no impairment) to 1 (severe impairment). Total or domain score change of >=0.5 are considered clinically meaningful.
Measured: Immediately following the first administration of study drug through Study Week 56
Change From Baseline to Week 56 in EQ-5D-5L VAS
EQ-5D-5L VAS is to rate current health status on a scale of 0-100, with 0 being the worst imaginable health state.
Measured: Immediately following the first administration of study drug through Study Week 56
Mean Work Productivity Loss Due to Asthma
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Work productivity loss is derived by sum of percentage of missed work due to asthma and product of percentage of actual working hours times degree of asthma affecting work productivity while working. Percentage of missed work due to asthma is calculated by number of hours missed work due to asthma divided by total number of hours missed work plus number of hours actually worked. This is only applicable to patients who were employed.
Measured: Immediately following the first administration of study drug through Study Week 56
Mean Productivity Loss Due to Asthma in Classroom
WPAI+CIQ (Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire) contains 10 questions. Classroom productivity loss is derived by sum of percentage of missed classes due to asthma and product of percentage of actual hours attending classes times degree of asthma affecting classroom productivity. Percentage of missed classes due to asthma is calculated by number of hours missed classes due to asthma divided by total number of hours missed classes plus number of hours actually attending classes. This is only applicable for patients who took classes.
Measured: Immediately following the first administration of study drug through Study Week 56
Number of Participants That Utilized Health Care Resources
Measured: Immediately following the first administration of study drug through Study Week 56
Patient and Clinician Assessment of Response to Treatment
CGIC (clinician global impression of change), and PGIC (patient global impression of change) are overall evaluation of response to treatment, conducted separately by investigator and patient using a 7-point rating scale, ranging from 1 (Very much Improved), to 7 (Very much Worse). This endpoint was added after the second protocol amendment, thus not all patients had data to be analyzed.
Measured: Immediately following the first administration of study drug through Study Week 56

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Aug 2013Mar 2016

First posted2 Aug 2013 (estimated)
Study startAug 2013
Primary completionMar 2016
Study completionMar 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (10)Papers the sponsor has linked to this study.
Other trials for AsthmaStudies of the same condition, open and under way.
More trials run by AstraZenecaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 2,508 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01914757
Sponsor's protocol ID: D3250C00018
Status last verified: Nov 2016
First submitted: 31 Jul 2013
Last updated: 25 Jan 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 35287231
Lugogo 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.
PubMed 32334141
Jackson 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.
PubMed 31836949
Chipps 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.
PubMed 31626906
Chupp 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.
PubMed 30802500
Bleecker 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.
PubMed 30139780
DuBuske 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.
PubMed 30077185
Chipps 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.
PubMed 29409951
Ohta 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.
PubMed 29128192
FitzGerald 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.
PubMed 27609406

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT01914757
Acronym / sponsor ID: D3250C00018
Conditions: Asthma
Keywords: Asthma, Bronchial Diseases, Respiratory Tract Diseases, Lung Diseases, Obstructive Lung Diseases
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 2,508 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: Aug 2013
Primary completion: Mar 2016 (actual)
Study completion: Mar 2016 (actual)
First posted: 2 Aug 2013 (estimated)
Results: Posted 25 Jan 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 3

Arm	Type	Receives
Benralizumab 30 mg q.4 weeks	Experimental	Biological: BenralizumabBenralizumab administered subcutaneously every 4 weeks
Benralizumab 30 mg q.8 weeks	Experimental	Biological: BenralizumabBenralizumab administered subcutaneously every 8 weeks
Placebo	Placebo comparator	Biological: PlaceboPlacebo administered subcutaneously

Who may qualify

Ages: 12 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (7 listed)

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:
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BenralizumabBenralizumab subcutaneously on study week 0 until study week 52 inclusive.	Biological	Benralizumab 30 mg q.4 weeks, Benralizumab 30 mg q.8 weeks
PlaceboPlacebo subcutaneously on study week 0 until study week 52 inclusive.	Biological	Placebo

Primary outcome

Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 56.
The annual exacerbation rate is based on unadjudicated annual exacerbation rate reported by the investigator in the eCRF.

22 secondary outcomes

Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils <300/uL
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Immediately following the first administration of study drug through Study Week 56.
Change in Asthma Rescue Medication Use
Time frame: Immediately following the first administration of study drug through Study Week 56.
Home Lung Function Assessments Based on PEF
Time frame: Immediately following the first administration of study drug through Study Week 56.
Proportion of Nights With Awakening Due to Asthma
Time frame: Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils >=300/uL
Time frame: Immediately following the first administration of study drug through Study Week 56.
Mean Change From Baseline to Week 56 in ACQ-6 for Patients With Baseline Eosinophils <300/uL
Time frame: Immediately following the first administration of study drug through Study Week 56.
Number of Patients With >=1 Asthma Exacerbation
Time frame: Immediately following the first administration of study drug through Study Week 56
Time to First Asthma Exacerbation
Time frame: Immediately following the first administration of study drug through Study Week 56
Annual Rate of Asthma Exacerbation Resulting Emergency Room Visits and Hospitalizations
Time frame: Immediately following the first administration of study drug through Study Week 56.
Pharmacokinetics of Benralizumab
Time frame: Baseline, Week 4, Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56, Week 60
Immunogenicity of Benralizumab
Time frame: Pre-treatment until end of follow-up
Extent of Exposure
Time frame: Immediately following the first administration of study drug through Study Week 56
Mean Change From Baseline to Week 56 in AQLQ(S)+12
Time frame: Immediately following the first administration of study drug through Study Week 56
Change From Baseline to Week 56 in EQ-5D-5L VAS
Time frame: Immediately following the first administration of study drug through Study Week 56
Mean Work Productivity Loss Due to Asthma
Time frame: Immediately following the first administration of study drug through Study Week 56
Mean Productivity Loss Due to Asthma in Classroom
Time frame: Immediately following the first administration of study drug through Study Week 56
Number of Participants That Utilized Health Care Resources
Time frame: Immediately following the first administration of study drug through Study Week 56
Patient and Clinician Assessment of Response to Treatment
Time frame: Immediately following the first administration of study drug through Study Week 56

Results and safety

Results posted to the registry on 25 Jan 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Benralizumab 30 mg q.4 Weeks	425	389
Benralizumab 30 mg q.8 Weeks	441	390
Placebo	440	402

Primary outcome: Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL

Time frame: Immediately following the first administration of study drug through Study Week 56.. Least squares mean (95% Confidence Interval). Unit: Events/year

Measure	Benralizumab 30 mg q.4 Weeks n = 241	Benralizumab 30 mg q.8 Weeks n = 239	Placebo n = 248
Value	0.6 (0.48 to 0.74)	0.66 (0.54 to 0.82)	0.93 (0.77 to 1.12)

Benralizumab 30 mg q.4 Weeks vs Placebo: Rate Ratio: 0.64 (95% CI 0.49 to 0.85), p = 0.002, Negative Binomial
Benralizumab 30 mg q.8 Weeks vs Placebo: Rate Ratio: 0.72 (95% CI 0.54 to 0.95), p = 0.019, Negative Binomial

Population analysed: Full analysis set, Baseline eosinophils \>=300/uL, High-dose ICS.

22 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Benralizumab 30 mg q.4 Weeks	46 of 438 (10.5%)	244 of 438 (55.7%)	Not reported
Benralizumab 30 mg q.8 Weeks	41 of 428 (9.6%)	232 of 428 (54.2%)	Not reported
Placebo	61 of 440 (13.9%)	264 of 440 (60%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35287231Menzies-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.
Derived from this study: PubMed 32334141Lugogo 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.
Derived from this study: PubMed 31836949Jackson 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.
Derived from this study: PubMed 31626906Chipps 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.
Derived from this study: PubMed 30802500Chupp 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.
Derived from this study: PubMed 30139780Bleecker 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.
Derived from this study: PubMed 30077185DuBuske 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.
Derived from this study: PubMed 29409951Chipps 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.
Derived from this study: PubMed 29128192Ohta 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.
Derived from this study: PubMed 27609406FitzGerald 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.
D3250C00018CSP3redactedLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark Fitzgerald, MD, PhD, Professor of Medicine principal investigator

The Lung Centre, Gordon and Leslie Diamond Health Care Centre, Vancouver Canada

214 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Benralizumab in people with Asthma, run by AstraZeneca at 214 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 214 sites in United States, Japan, Poland, Germany, Argentina and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annual Asthma Exacerbation Rate in Adult and Adolescent Patients With Uncontrolled Asthma for Patients With Baseline Eosinophils >=300/uL (time frame: Immediately following the first administration of study drug through Study Week 56.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01914757, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2017.