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

Asthma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01914757
• Other study ID #: D3250C00018
• Status: Completed
• Phase: Phase 3
• First received: July 31, 2013
• Last updated: April 11, 2016
• Start date: August 2013
• Est. completion date: March 2016

Study information

• Verified date: April 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review BoardCanada: Health CanadaChile: Instituto de Salud Pública de ChileJapan: Ministry of Health, Labor and WelfarePoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRomania: National Medicines AgencyUkraine: Ministry of HealthSweden: Medical Products AgencyGermany: Paul-Ehrlich-InstitutArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaPhilippines: Bureau of Food and Drugs
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2508
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures

2. Female and male aged 12 to 75 years, inclusively, at the time of Visit 1

3. 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.

4. 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.

Exclusion criteria:

1. 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)

2. 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

3. 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

4. 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Biological:
• Benralizumab
Benralizumab subcutaneously on study week 0 until study week 52 inclusive.
• Placebo
Placebo subcutaneously on study week 0 until study week 52 inclusive.
• Benralizumab (adolescent patients in the EU)
Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Locations

Country	Name	City	State
Argentina	Research Site	Buenos Aires
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autónoma de Bs. As.
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Concepción del Uruguay
Argentina	Research Site	Córdoba
Argentina	Research Site	Corrientes
Argentina	Research Site	Florida
Argentina	Research Site	Godoy Cruz
Argentina	Research Site	La Plata
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Ranelagh
Argentina	Research Site	Rosario
Argentina	Research Site	San Miguel de Tucuman
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Moncton	New Brunswick
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Quebec
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Chile	Research Site	Concepcion
Chile	Research Site	Quillota
Chile	Research Site	Santiago
Chile	Research Site	Talcahuano
Chile	Research Site	Valparaiso
Chile	Research Site	Viña del Mar
Germany	Research Site	Aschaffenburg
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Bonn
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt/Main
Germany	Research Site	Geesthacht
Germany	Research Site	Gelsenkirchen
Germany	Research Site	Hamburg
Germany	Research Site	Hannover
Germany	Research Site	Herford
Germany	Research Site	Leipzig
Germany	Research Site	Mainz
Germany	Research Site	München
Germany	Research Site	Neu-Isenburg
Germany	Research Site	Rostock
Germany	Research Site	Rüdersdorf
Germany	Research Site	Witten
Japan	Research Site	Asahi-shi
Japan	Research Site	Chiyoda-ku
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Itabashi-ku
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kokubunji-shi
Japan	Research Site	Matsue-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Mizunami-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Obihiro-shi
Japan	Research Site	Oita-shi
Japan	Research Site	Ota-shi
Japan	Research Site	Sagamihara-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sakaide-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Setagaya-ku
Japan	Research Site	Shibuya-ku
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Sumida-ku
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Tsukubo-gun
Japan	Research Site	Yokohama-shi
Philippines	Research Site	Iloilo City
Philippines	Research Site	Lipa City
Philippines	Research Site	Quezon City
Poland	Research Site	Aleksandrów Lódzki
Poland	Research Site	Bialystok
Poland	Research Site	Bielsko Biala
Poland	Research Site	Bydgoszcz
Poland	Research Site	Bystra Slaska
Poland	Research Site	Gdansk
Poland	Research Site	Gorzów Wlkp
Poland	Research Site	Karczew
Poland	Research Site	Katowice
Poland	Research Site	Koszalin
Poland	Research Site	Kraków
Poland	Research Site	Leczna
Poland	Research Site	Lódz
Poland	Research Site	Lubin
Poland	Research Site	Lublin
Poland	Research Site	Ostrów Wielkopolski
Poland	Research Site	Poznan
Poland	Research Site	Ruda Slaska
Poland	Research Site	Rzeszów
Poland	Research Site	Skierniewice
Poland	Research Site	Szczecin
Poland	Research Site	Tarnów
Poland	Research Site	Torun
Poland	Research Site	Warszawa
Poland	Research Site	Wielun
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Poland	Research Site	Zabrze
Poland	Research Site	Znin
Romania	Research Site	Bragadiru
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Constanta
Romania	Research Site	Deva
Romania	Research Site	Iasi
Romania	Research Site	Timisoara
Sweden	Research Site	Goteborg
Sweden	Research Site	Luleå
Sweden	Research Site	Lund
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Mykolayiv
Ukraine	Research Site	Uzhgorod
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Vinnytsya
Ukraine	Research Site	Zaporizhzhia
Ukraine	Research Site	Zaporozhye
United States	Research Site	Alhambra	California
United States	Research Site	Anaheim	California
United States	Research Site	Andalusia	Alabama
United States	Research Site	Arlington	Texas
United States	Research Site	Austin	Texas
United States	Research Site	Bangor	Maine
United States	Research Site	Beverly Hills	California
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boerne	Texas
United States	Research Site	Bronx	New York
United States	Research Site	Celebration	Florida
United States	Research Site	Centennial	Colorado
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbus	Ohio
United States	Research Site	Corvallis	Oregon
United States	Research Site	Covington	Louisiana
United States	Research Site	Dallas	Texas
United States	Research Site	Dayton	Ohio
United States	Research Site	Durham	North Carolina
United States	Research Site	Eagle	Idaho
United States	Research Site	Fairfax	Virginia
United States	Research Site	Falls Church	Virginia
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Flagstaff	Arizona
United States	Research Site	Flint	Michigan
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Mitchell	Kentucky
United States	Research Site	Fountain Valley	California
United States	Research Site	Gainesville	Georgia
United States	Research Site	Garden Grove	California
United States	Research Site	Glendale	Arizona
United States	Research Site	Henderson	Nevada
United States	Research Site	Hialeah	Florida
United States	Research Site	Homestead	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Indian Land	South Carolina
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jefferson Hills	Pennsylvania
United States	Research Site	Knoxville	Tennessee
United States	Research Site	Lakewood	California
United States	Research Site	Lehigh Acres	Florida
United States	Research Site	Lenexa	Kansas
United States	Research Site	Madison	Wisconsin
United States	Research Site	Miami	Florida
United States	Research Site	Middleburg Heights	Ohio
United States	Research Site	Midvale	Utah
United States	Research Site	Milwaukee	Wisconsin
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Murray	Utah
United States	Research Site	North Hollywood	California
United States	Research Site	Northridge	California
United States	Research Site	Ocala	Florida
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Ormond Beach	Florida
United States	Research Site	Palmdale	California
United States	Research Site	Phoenix	Arizona
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Portland	Oregon
United States	Research Site	Rancho Mirage	California
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Redondo Beach	California
United States	Research Site	Rolling Hills Estate	California
United States	Research Site	Roseville	California
United States	Research Site	Sacramento	California
United States	Research Site	San Antonio	Texas
United States	Research Site	Shiloh	Illinois
United States	Research Site	Smyrna	Georgia
United States	Research Site	St Louis	Missouri
United States	Research Site	Stockton	California
United States	Research Site	Thousand Oaks	California
United States	Research Site	Traverse City	Michigan
United States	Research Site	Tucson	Arizona
United States	Research Site	Union	New Jersey
United States	Research Site	Upland	California
United States	Research Site	Ventura	California
United States	Research Site	Virginia Gardens	Florida
United States	Research Site	Walnut Creek	California
United States	Research Site	Wheat Ridge	Colorado
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Woodland	California

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Argentina,  Canada,  Chile,  Germany,  Japan,  Philippines,  Poland,  Romania,  Sweden,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effect of benralizumab on asthma exacerbations in adult and adolescent patients with uncontrolled asthma.	Annual asthma exacerbation rate	Immediately following the first administration of study drug through Study Week 56.	No
Secondary	To assess the effect of benralizumab on pulmonary function	Endpoints: Pre-dose/pre-bronchodilator FEV1 and post-bronchodilator FEV1 at the study centre	Immediately following the first administration of study drug through Study Week 56.	No
Secondary	To assess the effect of benralizumab on asthma symptoms and other asthma control metrics (as per the ePRO)	Endpoints: - Asthma symptom score (total,daytime and night time) - Rescue medication use - Home lung function (morning and evening PEF) - Nights with awakening due to asthma - ACQ-6	Immediately following the first administration of study drug through Study Week 56.	No
Secondary	To assess the effect of benralizumab on emergency room visits and hospitalizations due to asthma	Annual rate of asthma exacerbations that are associated with an emergency room visit or a hospitalization	Immediately following the first administration of study drug through Study Week 56.	No
Secondary	To evaluate the pharmacokinetics and immunogenicity of benralizumab	Endpoints: - PK parameters- Anti-drug antibodies (ADA)	Immediately following the first administration of study drug through Study Week 56.	No
Secondary	To assess the safety and tolerability of benralizumab	Endpoints: - AE/SAE - Laboratory variables - ECG - Physical Examination	Immediately following the first administration of study drug through Study Week 56.	Yes
Secondary	To assess the effect of benralizumab on other parameters associated with asthma exacerbations	Endpoint: Time to first asthma exacerbation and proportion of patients with =1 asthma exacerbation	Immediately following the first administration of study drug through Study Week 56	No
Secondary	To assess the effect of benralizumab on asthma related and general health-related quality of life	Endpoints: - AQLQ(S)+12 - EQ-5D-5L	Immediately following the first administration of study drug through Study Week 56	No
Secondary	To evaluate the effect of benralizumab on health care resource utilization and productivity loss due to asthma	Endpoints: - WPAI+CIQ - Asthma specific resource utilization	Immediately following the first administration of study drug through Study Week 56	No
Secondary	To evaluate the overall response to treatment	Endpoints: - CGIC - PGIC	Immediately following the first administration of study drug through Study Week 56	No