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

NCT ID: NCT02155660

Last Updated: 2019-06-26

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2255 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-25

Study Completion Date

2018-04-09

Brief Summary

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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.

Detailed Description

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Conditions

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Moderate to Very Severe Chronic Obstructive Pulmonary Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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Benralizumab Arm A

Benralizumab administered subcutaneously

Group Type EXPERIMENTAL

Benralizumab Arm A

Intervention Type DRUG

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Benralizumab Arm B

Benralizumab administered subcutaneously

Group Type EXPERIMENTAL

Benralizumab Arm B

Intervention Type DRUG

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Benralizumab Arm C

Benralizumab administered subcutaneously

Group Type EXPERIMENTAL

Benralizumab Arm C

Intervention Type DRUG

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Placebo

Placebo administered subcutaneously

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Interventions

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Benralizumab Arm A

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Intervention Type DRUG

Benralizumab Arm B

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Intervention Type DRUG

Benralizumab Arm C

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Intervention Type DRUG

Placebo

Benralizumab subcutaneously on study week 0 until study week 48 inclusive

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

40 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role collaborator

AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bartolome R. Celli, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital, Pulmonary Division, 75 Francis Street, PBB Clinics 3, Boston, MA 02115

Locations

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Birmingham, Alabama, United States

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Gulf Shores, Alabama, United States

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Montgomery, Alabama, United States

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Flagstaff, Arizona, United States

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Phoenix, Arizona, United States

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Anaheim, California, United States

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Arcadia, California, United States

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Bakersfield, California, United States

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Fresno, California, United States

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Fullerton, California, United States

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Hawaiian Gardens, California, United States

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Huntington Beach, California, United States

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Los Angeles, California, United States

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Northridge, California, United States

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Palmdale, California, United States

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Peninsula, California, United States

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Placentia, California, United States

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Rolling Hills Estates, California, United States

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Westminster, California, United States

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Centennial, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Chiefland, Florida, United States

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Clearwater, Florida, United States

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Clearwater, Florida, United States

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Coconut Creek, Florida, United States

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Coral Gables, Florida, United States

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Daytona Beach, Florida, United States

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DeBary, Florida, United States

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DeLand, Florida, United States

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Doral, Florida, United States

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Edgewater, Florida, United States

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Fort Lauderdale, Florida, United States

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Hialeah, Florida, United States

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Hialeah, Florida, United States

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Hialeah, Florida, United States

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Homestead, Florida, United States

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Jacksonville, Florida, United States

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Kissimmee, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Miami, Florida, United States

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Pensacola, Florida, United States

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Port Charlotte, Florida, United States

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Sarasota, Florida, United States

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South Miami, Florida, United States

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Atlanta, Georgia, United States

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Blue Ridge, Georgia, United States

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Lawrenceville, Georgia, United States

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Woodstock, Georgia, United States

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Nampa, Idaho, United States

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Evergreen Park, Illinois, United States

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O'Fallon, Illinois, United States

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Peoria, Illinois, United States

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River Forest, Illinois, United States

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Topeka, Kansas, United States

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Henderson, Kentucky, United States

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Owensboro, Kentucky, United States

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Opelousas, Louisiana, United States

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Shreveport, Louisiana, United States

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Sunset, Louisiana, United States

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Bangor, Maine, United States

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Lutherville, Maryland, United States

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White Marsh, Maryland, United States

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Fall River, Massachusetts, United States

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Marlborough, Massachusetts, United States

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Buckley, Michigan, United States

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Kalamazoo, Michigan, United States

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Troy, Michigan, United States

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Edina, Minnesota, United States

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Fridley, Minnesota, United States

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Woodbury, Minnesota, United States

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Picayune, Mississippi, United States

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Port Gibson, Mississippi, United States

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Belton, Missouri, United States

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Florissant, Missouri, United States

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St Louis, Missouri, United States

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Missoula, Montana, United States

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Las Vegas, Nevada, United States

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Marlton, New Jersey, United States

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Union, New Jersey, United States

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Brooklyn, New York, United States

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Great Neck, New York, United States

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Mineola, New York, United States

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New Windsor, New York, United States

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New York, New York, United States

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Potsdam, New York, United States

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The Bronx, New York, United States

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The Bronx, New York, United States

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Burlington, North Carolina, United States

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Calabash, North Carolina, United States

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Charlotte, North Carolina, United States

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Hickory, North Carolina, United States

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Mooresville, North Carolina, United States

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New Bern, North Carolina, United States

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Shelby, North Carolina, United States

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Chardon, Ohio, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Columbus, Ohio, United States

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Marion, Ohio, United States

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Toledo, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Oklahoma City, Oklahoma, United States

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Clackamas, Oregon, United States

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Medford, Oregon, United States

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Monroeville, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Uniontown, Pennsylvania, United States

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Charleston, South Carolina, United States

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Hodges, South Carolina, United States

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Spartanburg, South Carolina, United States

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Rapid City, South Dakota, United States

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Tullahoma, Tennessee, United States

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Corsicana, Texas, United States

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Dallas, Texas, United States

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Duncanville, Texas, United States

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Fort Worth, Texas, United States

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Huntsville, Texas, United States

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Killeen, Texas, United States

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Lampasas, Texas, United States

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Longview, Texas, United States

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Lufkin, Texas, United States

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McKinney, Texas, United States

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McKinney, Texas, United States

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Plano, Texas, United States

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Sealy, Texas, United States

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Bountiful, Utah, United States

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Salt Lake City, Utah, United States

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Abingdon, Virginia, United States

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Richmond, Virginia, United States

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Richmond, Virginia, United States

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Everett, Washington, United States

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Tacoma, Washington, United States

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Kingwood, West Virginia, United States

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Morgantown, West Virginia, United States

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Buenos Aires, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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CABA, , Argentina

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Ciudad Autónoma de Buenos Aire, , Argentina

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Ciudad de Buenos Aires, , Argentina

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Concepción del Uruguay, , Argentina

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Corrientes, , Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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Florida, , Argentina

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Mar del Plata, , Argentina

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Mar del Plata, , Argentina

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Mendoza, , Argentina

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Mendoza, , Argentina

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Nueve de Julio, , Argentina

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Quilmes, , Argentina

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Rosario, , Argentina

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San Fernando, , Argentina

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San Juan Bautista, , Argentina

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San Miguel de Tucumán, , Argentina

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Clayton, , Australia

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Gosford, , Australia

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Murdoch, , Australia

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Nedlands, , Australia

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New Lambton, , Australia

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Woolloongabba, , Australia

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Brussels, , Belgium

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Genk, , Belgium

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Jambes, , Belgium

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Leuven, , Belgium

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Malmedy, , Belgium

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Turnhout, , Belgium

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Veurne, , Belgium

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Fortaleza, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Porto Alegre, , Brazil

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Rio de Janeiro, , Brazil

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Santo André, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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Sorocaba, , Brazil

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Vitória, , Brazil

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Dupnitsa, , Bulgaria

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Kozloduy, , Bulgaria

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Pazardzhik, , Bulgaria

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Pernik, , Bulgaria

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Petrich, , Bulgaria

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Plovdiv, , Bulgaria

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Rousse, , Bulgaria

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Sandanski, , Bulgaria

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Silistra, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Vidin, , Bulgaria

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Vratsa, , Bulgaria

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Yambol, , Bulgaria

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Curicó, , Chile

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Quillota, , Chile

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Santiago, , Chile

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Santiago, , Chile

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Talca, , Chile

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Armenia, , Colombia

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Barranquilla, , Colombia

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Bogotá, , Colombia

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Bogotá, , Colombia

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Bogotá, , Colombia

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Cali, , Colombia

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Manizales, , Colombia

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Medellín, , Colombia

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Medillin, , Colombia

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Petrinja, , Croatia

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Aarhus N, , Denmark

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København NV, , Denmark

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Næstved, , Denmark

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Odense C, , Denmark

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Roskilde, , Denmark

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Silkeborg, , Denmark

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Bois-Guillaume, , France

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Brest, , France

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La Tronche, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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Montpellier, , France

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Nîmes, , France

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Orléans, , France

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Pessac, , France

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Haifa, , Israel

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Jerusalem, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Rehovot, , Israel

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Tel Aviv, , Israel

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Durango, , Mexico

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Guadalajara, , Mexico

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Guadalajara, , Mexico

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México, , Mexico

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Monterrey, , Mexico

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Monterrey, , Mexico

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Auckland, , New Zealand

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Auckland, , New Zealand

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Dunedin, , New Zealand

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Greenlane, , New Zealand

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Hamilton West, , New Zealand

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Tauranga, , New Zealand

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Bodø, , Norway

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Kolbjørnsvik, , Norway

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Svelvik, , Norway

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Cusco, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Lima, , Peru

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Piura, , Peru

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Iloilo City, , Philippines

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Lipa City, , Philippines

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Manila, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Quezon City, , Philippines

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Bialystok, , Poland

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Bialystok, , Poland

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Gorzów Wlkp, , Poland

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Grodzisk Mazowiecki, , Poland

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Karczew, , Poland

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Katowice, , Poland

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Krakow, , Poland

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Ostrowiec Świętokrzyski, , Poland

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Ostrów Wielkopolski, , Poland

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Ruda Śląska, , Poland

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Skierniewice, , Poland

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Sosnowiec, , Poland

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Starachowice, , Poland

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Szczecin, , Poland

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Słupca, , Poland

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Trzebnica, , Poland

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Wroclaw, , Poland

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Wroclaw, , Poland

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Żnin, , Poland

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Belgrade, , Serbia

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Celje, , Slovenia

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Golnik, , Slovenia

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Kamnik, , Slovenia

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Ljubljana, , Slovenia

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Maribor, , Slovenia

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Gothenburg, , Sweden

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Gothenburg, , Sweden

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Helsingborg, , Sweden

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Lund, , Sweden

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Malmo, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Changhua, , Taiwan

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Kaohsiung City, , Taiwan

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Kaohsiung City, , Taiwan

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New Taipei City, , Taiwan

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Taichung, , Taiwan

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Taichung, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkoknoi, , Thailand

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Hat Yai, , Thailand

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Khon Kaen, , Thailand

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Muang,, , Thailand

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Nonthaburi, , Thailand

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Adana, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Bursa, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Mersin, , Turkey (Türkiye)

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Cherkasy, , Ukraine

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Chernivtsi, , Ukraine

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Chernivtsi, , Ukraine

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Dnipropetrovsk, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Lutsk, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhya, , Ukraine

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Zaporizhzhya, , Ukraine

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Zaporizhzhya, , Ukraine

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Can Tho, , Vietnam

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Hanoi, , Vietnam

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Ho Chi Minh City, , Vietnam

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Countries

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

References

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Criner GJ, Celli BR, Singh D, Agusti A, Papi A, Jison M, Makulova N, Shih VH, Brooks L, Barker P, Martin UJ, Newbold P. Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies. Lancet Respir Med. 2020 Feb;8(2):158-170. doi: 10.1016/S2213-2600(19)30338-8. Epub 2019 Sep 28.

Reference Type DERIVED
PMID: 31575508 (View on PubMed)

Criner GJ, Celli BR, Brightling CE, Agusti A, Papi A, Singh D, Sin DD, Vogelmeier CF, Sciurba FC, Bafadhel M, Backer V, Kato M, Ramirez-Venegas A, Wei YF, Bjermer L, Shih VH, Jison M, O'Quinn S, Makulova N, Newbold P, Goldman M, Martin UJ; GALATHEA Study Investigators; TERRANOVA Study Investigators. Benralizumab for the Prevention of COPD Exacerbations. N Engl J Med. 2019 Sep 12;381(11):1023-1034. doi: 10.1056/NEJMoa1905248. Epub 2019 May 20.

Reference Type DERIVED
PMID: 31112385 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

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Document Type: Statistical Analysis Plan

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Other Identifiers

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D3251C00004

Identifier Type: -

Identifier Source: org_study_id

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