Benralizumab Efficacy in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With Exacerbation History

Moderate to Very Severe Chronic Obstructive Pulmonary Disease Clinical Trial

— GALATHEA  

Official title:

Randomised, Double-blind, 56 Week Placebo-controlled, Parallel Group, Multicentre, Phase 3 Study to Evaluate the Efficacy and Safety of 2 Doses of Benralizumab in Patients With Moderate to Very Severe COPD With a History of Exacerbations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02138916
• Other study ID #: D3251C00003
• Status: Completed
• Phase: Phase 3
• Start date: June 13, 2014
• Est. completion date: April 10, 2018

Study information

• Verified date: June 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine if benralizumab reduces COPD exacerbation rate in symptomatic patients with moderate to very severe COPD who are receiving standard of care therapies

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1656
• Est. completion date: April 10, 2018
• Est. primary completion date: April 10, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion Criteria:1.Informed consent. 2.Subjects 40-85 y.o. 3.Moderate to very severe COPD with Post Bronchodilator (BD) FEV1>20% and =65%. 4.=2 moderate or =1 severe COPD exacerbation(s) required treatment or hospitalization within 2-52 weeks prior to Visit1. 5. Modified Medical Research Council (mMRC) score =1 at Visit 1. 6.Treatment with double or triple therapy throughout the year prior to Visit 1, constant 2 weeks prior to Visit 1. 7.Tobacco history of =10 pack-years. 8.Women of childbearing potential must use a highly effective form of birth control from Visit 1 until 16 weeks after their last dose, and negative serum pregnancy test result at Visit 1. 9.Male subjects who are sexually active must be surgically sterile one year prior to Visit 1 or use an adequate method of contraception from the first Investigational Product (IP) dose until 16 weeks after their last dose. 10.Compliance with maintenance therapy during run-in =70%. 11. Blood eosinophils due to subject's stratification and cap for blood eosinophil levels.When any eosinophil cohort is full, subjects in the completed cohort will not be randomised and will be withdrawn from the study. Exclusion criteria: 1. Clinically important pulmonary disease other than COPD or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.

2. Any disorder or major physical impairment that is not stable by Investigator opinion and/or could affect: - subject safety-study findings or their interpretation or subject's ability to complete the entire study duration.

3. Unstable ischemic heart disease, arrhythmia, cardiomyopathy, or other relevant cardiovascular disorder that in Investigator's judgment may put the patient at risk or negatively affect the study outcome.

4. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 2 weeks prior to Visit1 or during the enrolment and run-in period.

5. Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 2 weeks prior to Visit1or during the enrolment and run-in period.

6. Pneumonia within 8 weeks prior to Visit1 or during the enrolment and run-in period.

7. Pregnant, breastfeeding, or lactating women. 8. Risk factors for pneumonia 9. History of anaphylaxis to any other biologic therapy. 10. Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right ventricular failure.

11. Use of immunosuppressive medication within 2 weeks prior to Visit1 and/or during the enrolment and run-in period.

12. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit 1.

13. Evidence of active tuberculosis (TB) without an appropriate course of treatment.

14. Lung volume reduction surgery within the 6 months prior to Visit 1. History of partial or total lung resection (single lobe or segmentectomy is acceptable).

15. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines.

16. Previous treatment with benralizumab. 17. Helminth parasitic infection diagnosed within 24 weeks prior to Visit 1.

Related Conditions & MeSH terms

• Lung Diseases
• Lung Diseases, Obstructive
• Moderate to Very Severe Chronic Obstructive Pulmonary Disease
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Benralizumab Arm A
Benralizumab subcutaneously on study week 0 until study week 48 inclusive
• Benralizumab Arm B
Benralizumab subcutaneously on study week 0 until study week 48 inclusive
• Placebo
Placebo subcutaneously on study week 0 until study week 48 inclusive

Locations

Country	Name	City	State
Austria	Research Site	Feldkirch
Austria	Research Site	Graz
Austria	Research Site	Innsbruck
Austria	Research Site	Linz
Austria	Research Site	Salzburg
Austria	Research Site	Wels
Austria	Research Site	Wien
Canada	Research Site	Ajax	Ontario
Canada	Research Site	Burlington	Ontario
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Grimsby	Ontario
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Pointe-Claire	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec
Canada	Research Site	Quebec City	Quebec
Canada	Research Site	Saskatoon	Saskatchewan
Canada	Research Site	Sherwood Park	Alberta
Canada	Research Site	St Charles Borromee	Quebec
Canada	Research Site	Trois Rivieres	Quebec
Canada	Research Site	Vancouver	British Columbia
Canada	Research Site	Vancouver	British Columbia
Czechia	Research Site	Jindrichuv Hradec
Czechia	Research Site	Karlovy Vary
Czechia	Research Site	Kralupy nad Vltavou
Czechia	Research Site	Mlada Boleslav
Czechia	Research Site	Olomouc
Czechia	Research Site	Praha 8
Czechia	Research Site	Rokycany
Czechia	Research Site	Strakonice
Czechia	Research Site	Teplice
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Berlin
Germany	Research Site	Bonn
Germany	Research Site	Frankfurt
Germany	Research Site	Frankfurt am Main
Germany	Research Site	Frankfurt/Main
Germany	Research Site	Geesthacht
Germany	Research Site	Hamburg
Germany	Research Site	Leipzig
Germany	Research Site	Marburg
Germany	Research Site	Neu-Isenburg
Germany	Research Site	Rodgau-Dudenhofen
Germany	Research Site	Teuchern
Germany	Research Site	Witten
Hungary	Research Site	Balassagyarmat
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Edelény
Hungary	Research Site	Farkasgyepü
Hungary	Research Site	Gödöllo
Hungary	Research Site	Hajdúnánás
Hungary	Research Site	Hatvan
Hungary	Research Site	Mátraháza
Hungary	Research Site	Miskolc
Hungary	Research Site	Pécs
Hungary	Research Site	Pécs
Hungary	Research Site	Százhalombatta
Hungary	Research Site	Szeged
Hungary	Research Site	Székesfehérvár
Italy	Research Site	Bolzano
Italy	Research Site	Catania
Italy	Research Site	Ferrara
Italy	Research Site	Genova
Italy	Research Site	Orbassano
Italy	Research Site	Palermo
Italy	Research Site	Parma
Italy	Research Site	Pavia
Italy	Research Site	Pisa
Italy	Research Site	Tradate
Japan	Research Site	Chuo-ku
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Fukuyama-shi
Japan	Research Site	Higashiibaraki-gun
Japan	Research Site	Himeji-shi
Japan	Research Site	Himeji-shi
Japan	Research Site	Hirosaki-shi
Japan	Research Site	Iwata-shi
Japan	Research Site	Izumo-shi
Japan	Research Site	Joyo-shi
Japan	Research Site	Kagoshima-shi
Japan	Research Site	Kasuga-shi
Japan	Research Site	Kasugai-shi
Japan	Research Site	Kawaguchi-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kiryu-shi
Japan	Research Site	Kishiwada-shi
Japan	Research Site	Kitakami-shi
Japan	Research Site	Kobe-shi
Japan	Research Site	Kochi-shi
Japan	Research Site	Kodaira-shi
Japan	Research Site	Kokubunji-shi
Japan	Research Site	Koshi-shi
Japan	Research Site	Kuki-shi
Japan	Research Site	Kumamoto-shi
Japan	Research Site	Kurashiki-shi
Japan	Research Site	Kurume-shi
Japan	Research Site	Kyoto-shi
Japan	Research Site	Matsue-shi
Japan	Research Site	Matsue-shi
Japan	Research Site	Matsumoto-shi
Japan	Research Site	Matsusaka-shi
Japan	Research Site	Meguro-ku
Japan	Research Site	Mizunami-shi
Japan	Research Site	Morioka-shi
Japan	Research Site	Nagaoka-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Nagoya-shi
Japan	Research Site	Niigata-shi
Japan	Research Site	Obihiro-shi
Japan	Research Site	Ohota-ku
Japan	Research Site	Ota-shi
Japan	Research Site	Saiki-shi
Japan	Research Site	Sakai-shi
Japan	Research Site	Sakaide-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sapporo-shi
Japan	Research Site	Sendai-shi
Japan	Research Site	Seto-shi
Japan	Research Site	Shinagawa-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Takamatsu-shi
Japan	Research Site	Takatsuki-shi
Japan	Research Site	Toon-shi
Japan	Research Site	Toshima-ku
Japan	Research Site	Ube-shi
Japan	Research Site	Ueda-shi
Japan	Research Site	Uji-shi
Japan	Research Site	Urasoe-shi
Japan	Research Site	Uruma-shi
Japan	Research Site	Yachiyo-shi
Japan	Research Site	Yanagawa-shi
Japan	Research Site	Yao-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Japan	Research Site	Yokohama-shi
Korea, Republic of	Research Site	Bucheon-si
Korea, Republic of	Research Site	Daegu
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Seoul
Korea, Republic of	Research Site	Wonju-si
Netherlands	Research Site	Breda
Netherlands	Research Site	Eindhoven
Netherlands	Research Site	Heerlen
Netherlands	Research Site	Horn
Netherlands	Research Site	Nijmegen
Netherlands	Research Site	Zwolle
Poland	Research Site	Bydgoszcz
Poland	Research Site	Dobre Miasto
Poland	Research Site	Gdansk
Poland	Research Site	Gdansk
Poland	Research Site	Katowice
Poland	Research Site	Koscian
Poland	Research Site	Kraków
Poland	Research Site	Kraków
Poland	Research Site	Lódz
Poland	Research Site	Lublin
Poland	Research Site	Lublin
Poland	Research Site	Lublin
Poland	Research Site	Mragowo
Poland	Research Site	Mrozy
Poland	Research Site	Olsztyn
Poland	Research Site	Proszowice
Poland	Research Site	Radom
Poland	Research Site	Ruda Slaska
Poland	Research Site	Rzeszów
Poland	Research Site	Tarnów
Poland	Research Site	Warszawa
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Poland	Research Site	Zakopane
Romania	Research Site	Bragadiru
Romania	Research Site	Brasov
Romania	Research Site	Bucharest
Romania	Research Site	Bucharest
Romania	Research Site	Constanta
Romania	Research Site	Deva
Romania	Research Site	Iasi
Romania	Research Site	Timisoara
Russian Federation	Research Site	Chelyabinsk
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ekaterinburg
Russian Federation	Research Site	Ivanovo
Russian Federation	Research Site	Izhevsk
Russian Federation	Research Site	Kazan
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Kemerovo
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Moscow
Russian Federation	Research Site	Nizhny Novgorod
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Novosibirsk
Russian Federation	Research Site	Penza
Russian Federation	Research Site	Perm
Russian Federation	Research Site	Pskov
Russian Federation	Research Site	Pyatigorsk
Russian Federation	Research Site	Ryazan
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saint-Petersburg
Russian Federation	Research Site	Saratov
Russian Federation	Research Site	Smolensk
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St. Petersburg
Russian Federation	Research Site	St.Petersburg
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Tomsk
Russian Federation	Research Site	Ufa
Russian Federation	Research Site	Ulyanovsk
Russian Federation	Research Site	Vladikavkaz
Russian Federation	Research Site	Vladimir
Russian Federation	Research Site	Volgograd
Russian Federation	Research Site	Volgograd
South Africa	Research Site	Amanzimtoti
South Africa	Research Site	Bloemfontein
South Africa	Research Site	Cape Town
South Africa	Research Site	Durban
South Africa	Research Site	Gauteng
South Africa	Research Site	Middelburg
Spain	Research Site	Alicante
Spain	Research Site	Badalona(Barcelona)
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Madrid
Spain	Research Site	Málaga
Spain	Research Site	Palma de Mallorca
Spain	Research Site	Sabadell (Barcelona)
Spain	Research Site	Santander
Spain	Research Site	Valencia
Switzerland	Research Site	Basel
Switzerland	Research Site	Biel
Switzerland	Research Site	Gossau
Switzerland	Research Site	Liestal
Switzerland	Research Site	St. Gallen
United Kingdom	Research Site	Aberdeen
United Kingdom	Research Site	Birmingham
United Kingdom	Research Site	Bradford
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Chertsey
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Glasgow
United Kingdom	Research Site	Le3 9qp
United Kingdom	Research Site	London
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Manchester
United Kingdom	Research Site	Newcastle-Under-Lyme
United Kingdom	Research Site	Newcastle-Upon-Tyne
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Plymouth
United Kingdom	Research Site	Southampton
United Kingdom	Research Site	Wishaw
United Kingdom	Research Site	Wolverhampton
United States	Research Site	Albuquerque	New Mexico
United States	Research Site	Altoona	Pennsylvania
United States	Research Site	Andalusia	Alabama
United States	Research Site	Arlington	Texas
United States	Research Site	Asheville	North Carolina
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Illinois
United States	Research Site	Austin	Texas
United States	Research Site	Baltimore	Maryland
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bend	Oregon
United States	Research Site	Beverly Hills	California
United States	Research Site	Birmingham	Alabama
United States	Research Site	Birmingham	Alabama
United States	Research Site	Boerne	Texas
United States	Research Site	Boynton Beach	Florida
United States	Research Site	Brandon	Florida
United States	Research Site	Bronxville	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Buffalo	New York
United States	Research Site	Calhoun	Georgia
United States	Research Site	Canton	Ohio
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chattanooga	Tennessee
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clearwater	Florida
United States	Research Site	Clearwater	Florida
United States	Research Site	Columbia	Maryland
United States	Research Site	Columbia	South Carolina
United States	Research Site	Dayton	Ohio
United States	Research Site	Decatur	Georgia
United States	Research Site	Dothan	Alabama
United States	Research Site	Duluth	Georgia
United States	Research Site	Durham	North Carolina
United States	Research Site	Eagle	Idaho
United States	Research Site	Elizabeth City	North Carolina
United States	Research Site	Erie	Pennsylvania
United States	Research Site	Evanston	Illinois
United States	Research Site	Farmington Hills	Michigan
United States	Research Site	Fayetteville	New York
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Mitchell	Kentucky
United States	Research Site	Franklin	Tennessee
United States	Research Site	Frisco	Texas
United States	Research Site	Gaffney	South Carolina
United States	Research Site	Gainesville	Florida
United States	Research Site	Galveston	Texas
United States	Research Site	Gastonia	North Carolina
United States	Research Site	Gold River	California
United States	Research Site	Greensboro	North Carolina
United States	Research Site	Greenville	South Carolina
United States	Research Site	Hazard	Kentucky
United States	Research Site	Hendersonville	Tennessee
United States	Research Site	Hialeah	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Huntington Beach	California
United States	Research Site	Huntington Park	California
United States	Research Site	Indian Land	South Carolina
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jasper	Alabama
United States	Research Site	Jefferson Hills	Pennsylvania
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lakewood	California
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Lomita	California
United States	Research Site	Loxahatchee Groves	Florida
United States	Research Site	Marietta	Georgia
United States	Research Site	McAllen	Texas
United States	Research Site	Medford	Oregon
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami Springs	Florida
United States	Research Site	Michigan City	Indiana
United States	Research Site	Midvale	Utah
United States	Research Site	Minneapolis	Minnesota
United States	Research Site	Mount Airy	North Carolina
United States	Research Site	Mount Pleasant	South Carolina
United States	Research Site	New Bern	North Carolina
United States	Research Site	New Haven	Connecticut
United States	Research Site	New York	New York
United States	Research Site	New York	New York
United States	Research Site	Newport Beach	California
United States	Research Site	North Dartmouth	Massachusetts
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Orlando	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Orlando	Florida
United States	Research Site	Palm Desert	California
United States	Research Site	Palo Alto	California
United States	Research Site	Panama City	Florida
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port Orange	Florida
United States	Research Site	Portland	Oregon
United States	Research Site	Provo	Utah
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Richland	Washington
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	Riverside	California
United States	Research Site	Rochester	Michigan
United States	Research Site	Rock Hill	South Carolina
United States	Research Site	Sacramento	California
United States	Research Site	Saint Charles	Missouri
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	Saint Petersburg	Florida
United States	Research Site	San Antonio	Texas
United States	Research Site	San Antonio	Texas
United States	Research Site	San Diego	California
United States	Research Site	Santa Ana	California
United States	Research Site	Sebring	Florida
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Summit	New Jersey
United States	Research Site	Thousand Oaks	California
United States	Research Site	Torrance	California
United States	Research Site	Tyler	Texas
United States	Research Site	Valparaiso	Indiana
United States	Research Site	Vero Beach	Florida
United States	Research Site	Waterbury	Connecticut
United States	Research Site	Wilmington	North Carolina
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winston-Salem	North Carolina
United States	Research Site	Winter Park	Florida
United States	Research Site	Wyomissing	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	MedImmune LLC

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Czechia,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL	A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or; Use of antibiotics; and/or; An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	From first IP to week 56
Secondary	Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL	A COPD exacerbation is defined by symptomatic worsening of COPD requiring: Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or; Use of antibiotics; and/or; An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	From first IP to week 56
Secondary	Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL	Pre-bronchodilator FEV1 (L) is collected at Weeks 0, 4, 8, 16, 24, 32, 40, 48, and 56. Baseline is the last non-missing value with quality (acceptable or borderline quality grade) prior to the first dose of study treatment.	First IP up to end of treatment Week 56
Secondary	Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL	SGRQ is from 50-item PRO instrument. The SGRQ total score is expressed as a percentage of overall impairment, in which 100% means the worst possible health status and 0 indicates the best possible health status.	First IP up to Week 56
Secondary	Mean Change From Baseline in CAT Total Score for Patients With Baseline EOS>=220/uL	CAT is an 8-item PRO developed to measure the impact of COPD on health status. The instrument uses semantic differential six-point response scales. A CAT total score is the sum of item responses. Score ranges from 0 to 40 with higher scores indicative of greater COPD impact on health status.	First IP up to Week 56
Secondary	Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL	The E-RS: COPD is an 11-item PRO developed to evaluate the severity of respiratory symptoms of COPD. Summation of E-RS: COPD item responses produces a total score ranging from 0 to 40, with higher scores indicating greater severity.	First IP up to Week 56
Secondary	Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL	The number of rescue medication inhalations and nebulizer treatments taken are recorded by the patient in the eDiary twice daily. Total rescue medication use is the sum of daytime and night-time use.	First IP up to Week 56
Secondary	Mean Change From Baseline in Proportion of Nights Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL	Change from baseline to week 56 in proportion of nights awakenings due to respiratory symptoms.	First IP up to Week 56
Secondary	Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while onsidering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Exacerbation event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score =9 for 3 days or =12 for 2 days indicate an exacerbation event has occurred.	Immediately following first IP up to week 56
Secondary	Severity of EXACT-PRO for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while onsidering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Severity for the study is the highest score of EXACT-PRO.	Immediately following first IP up to week 56
Secondary	Duration of EXACT-PRO for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while onsidering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score =9 for 3 days or =12 for 2 days indicate an event has occurred. Calculation of event duration after identification of the following five parameters: 1) onset; 2) three-day rolling average; 3) maximum observed value; 4) threshold for improvement; and 5) recovery. That is, duration of the exacerbation is the time elapse between onset and recovery of the event.	Immediately following first IP up to week 56
Secondary	Annual EXACT-PRO Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL	The EXACT-PRO is a 14-item PRO instrument developed to assess the frequency, severity and duration of COPD exacerbations. Respondents are instructed to complete the electronic diary (eDiary) each evening just prior to bedtime and to answer the questions while onsidering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Event frequency is calculated by comparing the baseline with daily total scores. An increase in EXACT-PRO total score =9 for 3 days or =12 for 2 days indicate an event has occurred. Annual EXACT-PRO exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	Immediately following first IP up to week 56
Secondary	Number of Participants Having at Least 1 COPD Exacerbation for Patients With Baseline EOS>=220/uL	A COPD exacerbation is defined by symptomatic worsening COPD requiring systemic corticosteroids, antibiotics, or an inpatient hospitalization/death due to COPD.	Immediately following first IP up to week 56
Secondary	Time to First COPD Exacerbation	Time to first COPD exacerbation is from the randomization date to the first occurrence of COPD exacerbation	Immediately following first IP up to week 56
Secondary	Annual COPD Exacerbation Rate Associated With ER or Hospitalization Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL	Annual COPD exacerbations rate that result in ER or hospitalization is calculated by number of exacerbations resulting ER or hospitalization divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.	Immediately following first IP up to week 56
Secondary	Number of Participants Had COPD-related Healthcare Encounter for Patient With Baseline EOS>=220/uL	Types of healthcare encounter: Hospitalisations (inc. intensive care and/or general care), Emergency department visits, Unscheduled outpatients visits, Home visits, Telephone calls, and ambulance transports.	Immediately following first IP up to week 56
Secondary	Duration of Study Treatment Administration	Duration of study treatment is calculated from first dose date to last dose date + 1 day.	From first dose date to last dose date, 48 weeks per protocol.
Secondary	Serum Concentration of Benralizumab	PK serum samples were collected pre-dose at each visit.	Pre-first dose and pre-dose at end of treatment (week 56)
Secondary	Immunogenicity of Benralizumab	Antidrug antibody (ADA) responses such as ADA prevalence, ADA incidence, ADA persistently positive counts, etc. were presented	Pre-treatment until end of follow-up, week 60 per protocol.

External Links

•   Clinical Study protocol
•   Statistical Analysis Plan (SAP)