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

Moderate to Very Severe Chronic Obstructive Pulmonary Disease Clinical Trial

— TERRANOVA  

Official title:

A Randomised, Double-blind, Double Dummy, 56 Week Placebo-controlled, Multicentre, Parallel Group, Phase 3 Study Evaluating Efficacy/Safety of 3 Benralizumab Doses in Patients With Moderate to Very Severe COPD With Previous Exacerbations.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02155660
• Other study ID #: D3251C00004
• Status: Completed
• Phase: Phase 3
• Start date: June 25, 2014
• Est. completion date: April 9, 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: 2255
• Est. completion date: April 9, 2018
• Est. primary completion date: April 9, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

Inclusion Criteria:.

• Informed consent.

• Subjects 40-85 y.o.

• Moderate to very severe COPD with Post Bronchodilator (BD) FEV1>20% and =65%.

-=2 moderate or =1 severe COPD exacerbation(s) required treatment or hospitalization within 2-52 weeks prior to Visit1.

• Modified Medical Research Council (mMRC) score =1 at Visit 1.

• Treatment with double or triple therapy throughout the year prior to Visit 1, constant 2 weeks prior to Visit 1.

• Tobacco history of =10 pack-years.

• 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.

• 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.

• Compliance with maintenance therapy during run-in =70%.

• 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levels.When any eosinophil cohort is full, subjects in the completed cohort will not be randomised and will be withdrawn from the study.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:

• Clinically important pulmonary disease other than COPD or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.

• 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.

• 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.

• 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.

• Acute upper or lower respiratory infection requiring antibiotics within 2 weeks prior to Visit1 or during the enrolment and run-in period.

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

• Pregnant, breastfeeding, or lactating women.

• Risk factors for pneumonia

• History of anaphylaxis to any other biologic therapy.

• Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right ventricular failure.

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

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

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

• 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).

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

• Previous treatment with benralizumab.

• 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
• Benralizumab Arm C
Benralizumab subcutaneously on study week 0 until study week 48 inclusive
• Placebo
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	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Caba
Argentina	Research Site	Ciudad Autónoma de Buenos Aire
Argentina	Research Site	Ciudad de Buenos Aires
Argentina	Research Site	Concepción del Uruguay
Argentina	Research Site	Córdoba
Argentina	Research Site	Córdoba
Argentina	Research Site	Corrientes
Argentina	Research Site	Florencio Varela
Argentina	Research Site	Florida
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mar del Plata
Argentina	Research Site	Mendoza
Argentina	Research Site	Mendoza
Argentina	Research Site	Nueve de julio
Argentina	Research Site	Quilmes
Argentina	Research Site	Rosario
Argentina	Research Site	San Fernando
Argentina	Research Site	San Miguel de Tucuman
Australia	Research Site	Clayton
Australia	Research Site	Gosford
Australia	Research Site	Murdoch
Australia	Research Site	Nedlands
Australia	Research Site	New Lambton
Australia	Research Site	Woolloongabba
Belgium	Research Site	Brussels
Belgium	Research Site	Genk
Belgium	Research Site	Jambes
Belgium	Research Site	Leuven
Belgium	Research Site	Malmedy
Belgium	Research Site	Turnhout
Belgium	Research Site	Veurne
Brazil	Research Site	Fortaleza
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Rio de Janeiro
Brazil	Research Site	Santo Andre
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sao Paulo
Brazil	Research Site	Sorocaba
Brazil	Research Site	Vitória
Bulgaria	Research Site	Dupnitsa
Bulgaria	Research Site	Kozloduy
Bulgaria	Research Site	Pazardzhik
Bulgaria	Research Site	Pernik
Bulgaria	Research Site	Petrich
Bulgaria	Research Site	Plovdiv
Bulgaria	Research Site	Ruse
Bulgaria	Research Site	Sandanski
Bulgaria	Research Site	Silistra
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Sofia
Bulgaria	Research Site	Vidin
Bulgaria	Research Site	Vratsa
Bulgaria	Research Site	Yambol
Chile	Research Site	Curico
Chile	Research Site	Quillota
Chile	Research Site	Santiago
Chile	Research Site	Santiago
Chile	Research Site	Talca
Colombia	Research Site	Armenia
Colombia	Research Site	Barranquilla
Colombia	Research Site	Bogota
Colombia	Research Site	Bogotá
Colombia	Research Site	Bogotá
Colombia	Research Site	Cali
Colombia	Research Site	Manizales
Colombia	Research Site	Medellin
Colombia	Research Site	Medillin
Croatia	Research Site	Petrinja
Denmark	Research Site	Aarhus N
Denmark	Research Site	København NV
Denmark	Research Site	Næstved
Denmark	Research Site	Odense C
Denmark	Research Site	Roskilde
Denmark	Research Site	Silkeborg
France	Research Site	Bois Guillaume
France	Research Site	Brest Cedex
France	Research Site	La Tronche
France	Research Site	Lille cedex
France	Research Site	Lyon Cedex 04
France	Research Site	Marseille
France	Research Site	Montpellier
France	Research Site	NIMES Cedex 9
France	Research Site	Orléans Cedex 2
France	Research Site	Pessac
Israel	Research Site	Haifa
Israel	Research Site	Jerusalem
Israel	Research Site	Jerusalem
Israel	Research Site	Petach Tikva
Israel	Research Site	Rehovot
Israel	Research Site	Tel Aviv
Mexico	Research Site	Durango
Mexico	Research Site	Guadalajara
Mexico	Research Site	Guadalajara
Mexico	Research Site	Mexico
Mexico	Research Site	Monterrey
Mexico	Research Site	Monterrey
New Zealand	Research Site	Auckland
New Zealand	Research Site	Auckland
New Zealand	Research Site	Dunedin
New Zealand	Research Site	Greenlane
New Zealand	Research Site	Hamilton West
New Zealand	Research Site	Tauranga
Norway	Research Site	Bodø
Norway	Research Site	Kolbjørnsvik
Norway	Research Site	Svelvik
Peru	Research Site	Cusco
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Lima
Peru	Research Site	Piura
Philippines	Research Site	Iloilo City
Philippines	Research Site	Lipa City
Philippines	Research Site	Manila
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Philippines	Research Site	Quezon City
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Gorzów Wlkp
Poland	Research Site	Grodzisk Mazowiecki
Poland	Research Site	Karczew
Poland	Research Site	Katowice
Poland	Research Site	Kraków
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Poland	Research Site	Ruda Slaska
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Poland	Research Site	Slupca
Poland	Research Site	Sosnowiec
Poland	Research Site	Starachowice
Poland	Research Site	Szczecin
Poland	Research Site	Trzebnica
Poland	Research Site	Wroclaw
Poland	Research Site	Wroclaw
Poland	Research Site	Znin
Serbia	Research Site	Belgrade
Slovenia	Research Site	Celje
Slovenia	Research Site	Golnik
Slovenia	Research Site	Kamnik
Slovenia	Research Site	Ljubljana
Slovenia	Research Site	Maribor
Sweden	Research Site	Goteborg
Sweden	Research Site	Göteborg
Sweden	Research Site	Helsingborg
Sweden	Research Site	Lund
Sweden	Research Site	Malmo
Sweden	Research Site	Stockholm
Sweden	Research Site	Uppsala
Taiwan	Research Site	Changhua
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	Kaohsiung
Taiwan	Research Site	New-Taipei
Taiwan	Research Site	Taichung
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Taiwan	Research Site	Taipei
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Thailand	Research Site	Bangkok
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Thailand	Research Site	Khon Kaen
Thailand	Research Site	Muang,
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Turkey	Research Site	Adana
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Turkey	Research Site	Bursa
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
Turkey	Research Site	Izmir
Turkey	Research Site	Izmir
Turkey	Research Site	Mersin
Ukraine	Research Site	Cherkasy
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Chernivtsi
Ukraine	Research Site	Dnipropetrovsk
Ukraine	Research Site	Ivano-Frankivsk
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kharkiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Kyiv
Ukraine	Research Site	Lutsk
Ukraine	Research Site	Lviv
Ukraine	Research Site	Odesa
Ukraine	Research Site	Vinnytsia
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
Ukraine	Research Site	Zaporizhzhya
United States	Research Site	Abingdon	Virginia
United States	Research Site	Anaheim	California
United States	Research Site	Arcadia	California
United States	Research Site	Atlanta	Georgia
United States	Research Site	Bakersfield	California
United States	Research Site	Bangor	Maine
United States	Research Site	Belton	Missouri
United States	Research Site	Birmingham	Alabama
United States	Research Site	Blue Ridge	Georgia
United States	Research Site	Bountiful	Utah
United States	Research Site	Bronx	New York
United States	Research Site	Bronx	New York
United States	Research Site	Brooklyn	New York
United States	Research Site	Buckley	Michigan
United States	Research Site	Burlington	North Carolina
United States	Research Site	Calabash	North Carolina
United States	Research Site	Centennial	Colorado
United States	Research Site	Chardon	Ohio
United States	Research Site	Charleston	South Carolina
United States	Research Site	Charlotte	North Carolina
United States	Research Site	Chiefland	Florida
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Clackamas	Oregon
United States	Research Site	Clearwater	Florida
United States	Research Site	Clearwater	Florida
United States	Research Site	Coconut Creek	Florida
United States	Research Site	Colorado Springs	Colorado
United States	Research Site	Columbus	Ohio
United States	Research Site	Columbus	Ohio
United States	Research Site	Coral Gables	Florida
United States	Research Site	Corsicana	Texas
United States	Research Site	Dallas	Texas
United States	Research Site	Daytona Beach	Florida
United States	Research Site	DeBary	Florida
United States	Research Site	DeLand	Florida
United States	Research Site	Denver	Colorado
United States	Research Site	Doral	Florida
United States	Research Site	Duncanville	Texas
United States	Research Site	Edgewater	Florida
United States	Research Site	Edina	Minnesota
United States	Research Site	Everett	Washington
United States	Research Site	Evergreen Park	Illinois
United States	Research Site	Fall River	Massachusetts
United States	Research Site	Flagstaff	Arizona
United States	Research Site	Florissant	Missouri
United States	Research Site	Fort Lauderdale	Florida
United States	Research Site	Fort Worth	Texas
United States	Research Site	Fremont	Nebraska
United States	Research Site	Fresno	California
United States	Research Site	Fridley	Minnesota
United States	Research Site	Fullerton	California
United States	Research Site	Great Neck	New York
United States	Research Site	Gulf Shores	Alabama
United States	Research Site	Hawaiian Gardens	California
United States	Research Site	Henderson	Kentucky
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	Hialeah	Florida
United States	Research Site	Hickory	North Carolina
United States	Research Site	Hodges	South Carolina
United States	Research Site	Homestead	Florida
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
United States	Research Site	Houston	Texas
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	Huntsville	Texas
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kalamazoo	Michigan
United States	Research Site	Killeen	Texas
United States	Research Site	Kingwood	West Virginia
United States	Research Site	Kissimmee	Florida
United States	Research Site	Lampasas	Texas
United States	Research Site	Las Vegas	Nevada
United States	Research Site	Lawrenceville	Georgia
United States	Research Site	Longview	Texas
United States	Research Site	Los Angeles	California
United States	Research Site	Lufkin	Texas
United States	Research Site	Lutherville	Maryland
United States	Research Site	Marion	Ohio
United States	Research Site	Marlborough	Massachusetts
United States	Research Site	Marlton	New Jersey
United States	Research Site	McKinney	Texas
United States	Research Site	McKinney	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	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Miami	Florida
United States	Research Site	Mineola	New York
United States	Research Site	Missoula	Montana
United States	Research Site	Monroeville	Pennsylvania
United States	Research Site	Montgomery	Alabama
United States	Research Site	Mooresville	North Carolina
United States	Research Site	Morgantown	West Virginia
United States	Research Site	Nampa	Idaho
United States	Research Site	New Bern	North Carolina
United States	Research Site	New Windsor	New York
United States	Research Site	New York	New York
United States	Research Site	Northridge	California
United States	Research Site	O'Fallon	Illinois
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Oklahoma City	Oklahoma
United States	Research Site	Omaha	Nebraska
United States	Research Site	Opelousas	Louisiana
United States	Research Site	Owensboro	Kentucky
United States	Research Site	Palmdale	California
United States	Research Site	Peninsula	California
United States	Research Site	Pensacola	Florida
United States	Research Site	Peoria	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Picayune	Mississippi
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Placentia	California
United States	Research Site	Plano	Texas
United States	Research Site	Port Charlotte	Florida
United States	Research Site	Port Gibson	Mississippi
United States	Research Site	Potsdam	New York
United States	Research Site	Rapid City	South Dakota
United States	Research Site	Richmond	Virginia
United States	Research Site	Richmond	Virginia
United States	Research Site	River Forest	Illinois
United States	Research Site	Rolling Hills Estates	California
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Sarasota	Florida
United States	Research Site	Sealy	Texas
United States	Research Site	Shelby	North Carolina
United States	Research Site	Shreveport	Louisiana
United States	Research Site	South Miami	Florida
United States	Research Site	Spartanburg	South Carolina
United States	Research Site	Sunset	Louisiana
United States	Research Site	Tacoma	Washington
United States	Research Site	Toledo	Ohio
United States	Research Site	Topeka	Kansas
United States	Research Site	Troy	Michigan
United States	Research Site	Tullahoma	Tennessee
United States	Research Site	Union	New Jersey
United States	Research Site	Uniontown	Pennsylvania
United States	Research Site	Westminster	California
United States	Research Site	White Marsh	Maryland
United States	Research Site	Woodbury	Minnesota
United States	Research Site	Woodstock	Georgia
Vietnam	Research Site	Can Tho
Vietnam	Research Site	Hanoi
Vietnam	Research Site	Ho Chi Minh

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	MedImmune LLC

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Chile,  Colombia,  Croatia,  Denmark,  France,  Israel,  Mexico,  New Zealand,  Norway,  Peru,  Philippines,  Poland,  Serbia,  Slovenia,  Sweden,  Taiwan,  Thailand,  Turkey,  Ukraine, 

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.	Immediately following the first IP dose through 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.	Immediately following the first IP dose through 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 With Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL	Change from baseline to Week 56 in proportion of nights with 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 considering their experiences "today". The daily EXACT-PRO total score is recorded and has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is calculated based on comparison of the baseline score with daily total scores. An increase of EXACT-PRO total score =9 for 3 days or =12 for 2 days indicates a COPD 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 considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. Severity of the study is the highest score of EXACT-PRO.	Immediately following first IP up to week 56
Secondary	Duration of COPD Exacerbation Based on EXACT-PRO Score 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 considering their experiences "today". The daily EXACT-PRO total score has a range of 0-100 with higher scores indicative of greater severity. COPD exacerbation event frequency is identified by comparing the baseline score 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. Event duration is calculated 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 considering 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 the first IP dose through 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 dose 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 IP dose 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 the first IP dose through 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 dose 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	Anti-drug 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.

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