NCT04053634

Brief Summary

Phase 3 study to evaluate the efficacy and safety of a benralizumab in patients with moderate to very severe COPD with a history of frequent COPD exacerbations and elevated peripheral blood eosinophils (≥300/μL). Eligible patients must have a history of ≥2 moderate and/or severe COPD exacerbations in the previous year despite receiving triple (ICS/LABA/LAMA) background therapy for at least 3 months and ICS-based dual inhaled treatment for the remainder of the year. Eligible patients must also have an elevated blood eosinophil count. The treatment period will be of variable duration and will continue until the last patient has the opportunity to complete a minimum of 56 weeks, at which point all patients will complete the study. The primary endpoint will be analyzed at Week 56.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
689

participants targeted

Target at P50-P75 for phase_3 chronic-obstructive-pulmonary-disease

Timeline
Completed

Started Aug 2019

Longer than P75 for phase_3 chronic-obstructive-pulmonary-disease

Geographic Reach
29 countries

338 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 16, 2019

Completed
27 days until next milestone

First Posted

Study publicly available on registry

August 12, 2019

Completed
14 days until next milestone

Study Start

First participant enrolled

August 26, 2019

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 28, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 28, 2025

Completed
Last Updated

August 19, 2025

Status Verified

August 1, 2025

Enrollment Period

5.9 years

First QC Date

July 16, 2019

Last Update Submit

August 18, 2025

Conditions

Keywords

Chronic Obstructive Pulmonary DiseaseCOPDbenralizumabFasenraICSinhaled corticosteroidsexacerbationsLung DiseaseLABA/LAMA

Outcome Measures

Primary Outcomes (1)

  • Annualized rate of moderate or severe COPD exacerbations

    Moderate or severe COPD exacerbation is defined by symptomatic worsening of COPD requiring: * Use of systemic corticosteroids for at least 3 days; and/or * Use of antibiotics; and/or * An inpatient hospitalization or death due to COPD

    Over first 56 weeks

Secondary Outcomes (16)

  • Annualized rate of severe COPD exacerbations

    Minimum of 1 year and an average of 2 years

  • Annualized rate of COPD exacerbations that are associated with an emergency room/emergency department visit or a hospitalization

    Minimum of 1 year and an average of 2 years

  • Time to first COPD exacerbation

    During first 56 weeks

  • Change from baseline in SGRQ total and domain scores

    up to 56 weeks

  • Change from baseline in E-RS:COPD total and domain scores

    up to 56 weeks

  • +11 more secondary outcomes

Other Outcomes (1)

  • Safety and tolerability of benralizumab in patients with moderate to very severe COPD

    Minimum of 1 year and average of 2 years

Study Arms (2)

Benralizumab

EXPERIMENTAL

Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks

Biological: Benralizumab

Placebo

PLACEBO COMPARATOR

Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks

Biological: Placebo

Interventions

BenralizumabBIOLOGICAL

Benralizumab solution for injection in accessorized prefilled syringe (APFS) will be administered subcutaneously (SC) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks until the end of treatment.

Benralizumab
PlaceboBIOLOGICAL

Matching placebo will be administered subcutaneously with accessorized prefilled syringe (APFS) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks until the end of treatment.

Placebo

Eligibility Criteria

Age40 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of informed consent
  • Age 40 to 85 years
  • Male and/or female.
  • Current or former smoker with a tobacco history of ≥10 pack-years.
  • History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC\<0.70 and FEV1 ≤65% of predicted normal value.
  • Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment.
  • Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization.
  • Hospitalization is defined as an inpatient admission ≥24 hours
  • Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD.
  • At least one qualifying COPD exacerbation should occur while on stable uninterrupted triple therapy prior to enrolment.
  • Documented use of triple (ICS/LABA/LAMA) background therapy for COPD for ≥3 months immediately prior to enrollment.
  • Treatment with at least double inhaled therapy containing ICS (e.g. ICS/LABA or ICS/LAMA) for the remaining of 52 weeks prior to enrolment. Use of LABA/LAMA is allowed if ICS cannot be tolerated.
  • ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily.
  • Total cumulative duration of not being on double or triple background therapy must not exceed 2 months.
  • Stable therapy/doses for the last 3 months prior to randomization.
  • +5 more criteria

You may not qualify if:

  • Clinically important pulmonary disease other than COPD
  • Current diagnosis of asthma, prior history of asthma or asthma-COPD overlap according to GINA/GOLD. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18.
  • Radiological findings of a respiratory disease other than COPD contributing to respiratory symptoms. Solitary pulmonary nodules without appropriate follow up or findings of acute infection.
  • Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
  • Any unstable disorder that could affect patient safety, study findings or the patient's ability to complete the study.
  • Any clinically significant abnormal findings in physical examination, vital signs, ECG, laboratory tests could affect patient safety, study findings or the patient's ability to complete the study.
  • Cor pulmonale and/or right ventricular failure.
  • Long-term treatment with oxygen \>4.0 L/min and/or oxyhemoglobin saturation \<89% while breathing supplemental oxygen.
  • Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed.
  • Known immunodeficiency disorder, including positive HIV-1/2 testing.
  • Active liver disease. Chronic stable hepatitis B and C (including positive HBsAg or hepatitis C antibody testing), or other stable chronic liver disease are acceptable.
  • ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during the run-in period.
  • Helminth parasitic infection within 24 weeks prior to enrollment, not treated or failed to respond to standard of care therapy.
  • Alcohol or drug abuse within the past year, which may compromise the study data.
  • Malignancy, current or within the past 5 years, except for adequately treated non invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than 1 year prior to Visit 1. Suspected malignancy or undefined neoplasms.
  • +13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (343)

Research Site

Surprise, Arizona, 85374, United States

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Little Rock, Arkansas, 72209, United States

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Los Angeles, California, 90033, United States

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Los Angeles, California, 90048, United States

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Newport Beach, California, 92663, United States

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Northridge, California, 91324, United States

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Palm Springs, California, 92262, United States

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Westminster, California, 92683, United States

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Stamford, Connecticut, 06902, United States

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Clearwater, Florida, 33765, United States

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Daytona Beach, Florida, 32117, United States

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Edgewater, Florida, 32132, United States

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Jacksonville, Florida, 32204, United States

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Jacksonville, Florida, 32209, United States

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Kissimmee, Florida, 34741, United States

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Kissimmee, Florida, 34746, United States

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Leesburg, Florida, 34748, United States

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Miami, Florida, 33125, United States

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Orlando, Florida, 32819, United States

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Pensacola, Florida, 32503, United States

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St. Petersburg, Florida, 33707, United States

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Tampa, Florida, 33607, United States

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Winter Park, Florida, 32789, United States

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Lawrenceville, Georgia, 30046, United States

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Rincon, Georgia, 31326, United States

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Chicago, Illinois, 60611, United States

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O'Fallon, Illinois, 62269, United States

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Peoria, Illinois, 61636, United States

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Michigan City, Indiana, 46360, United States

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Iowa City, Iowa, 52242, United States

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Kansas City, Kansas, 66160, United States

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Georgetown, Kentucky, 40324, United States

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Baltimore, Maryland, 21224, United States

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Columbia, Maryland, 21044, United States

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Boston, Massachusetts, 02215, United States

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North Dartmouth, Massachusetts, 02747, United States

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Farmington Hills, Michigan, 48336, United States

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Lincoln, Nebraska, 68510, United States

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Omaha, Nebraska, 68124, United States

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Toms River, New Jersey, 08755, United States

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Buffalo, New York, 14215, United States

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New Windsor, New York, 12553, United States

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The Bronx, New York, 10461, United States

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Burlington, North Carolina, 27215, United States

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Charlotte, North Carolina, 28277, United States

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Elizabeth City, North Carolina, 27909, United States

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Gastonia, North Carolina, 28054, United States

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Mooresville, North Carolina, 28117, United States

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New Bern, North Carolina, 28562, United States

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Wilmington, North Carolina, 28401, United States

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Winston-Salem, North Carolina, 27103, United States

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Cleveland, Ohio, 44106, United States

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Columbus, Ohio, 43215, United States

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Oklahoma City, Oklahoma, 73106, United States

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Medford, Oregon, 97504, United States

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DuBois, Pennsylvania, 15801, United States

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Philadelphia, Pennsylvania, 19140, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Smithfield, Pennsylvania, 15478, United States

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Mt. Pleasant, South Carolina, 29464, United States

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North Charleston, South Carolina, 29406, United States

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Rock Hill, South Carolina, 29732, United States

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Rapid City, South Dakota, 57702, United States

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Chattanooga, Tennessee, 37404, United States

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Franklin, Tennessee, 37067, United States

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Hendersonville, Tennessee, 37075, United States

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Johnson City, Tennessee, 37601, United States

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Amarillo, Texas, 79106, United States

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Amarillo, Texas, 79124, United States

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Cypress, Texas, 77429, United States

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Dallas, Texas, 75390, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77079, United States

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Kerrville, Texas, 78028, United States

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San Antonio, Texas, 78258, United States

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Tomball, Texas, 77375, United States

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Salt Lake City, Utah, 84102, United States

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Abingdon, Virginia, 24210, United States

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Salem, Virginia, 24153, United States

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Williamsburg, Virginia, 23188, United States

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Everett, Washington, 98208, United States

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Spokane, Washington, 99204, United States

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Morgantown, West Virginia, 26505, United States

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Cudahy, Wisconsin, 53110, United States

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Buenos Aires, S2000PBJ, Argentina

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CABA, C1012AAR, Argentina

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Ciudad Autónoma de Buenos Aire, C1440BRR, Argentina

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Ciudad de Buenos Aires, 1425, Argentina

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Córdoba, X5003DCE, Argentina

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Florida, B1602DQD, Argentina

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Mar del Plata, B7600GWV, Argentina

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Mendoza, M5500CCG, Argentina

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San Fernando, B1646EBJ, Argentina

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San Juan Bautista, 1888, Argentina

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San Miguel de Tucumán, 4000, Argentina

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Caringbah, 2229, Australia

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Melbourne, 3004, Australia

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South Brisbane, 4101, Australia

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Southport, 4215, Australia

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Spearwood, 6163, Australia

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Bad Ischl, 4820, Austria

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Bludenz, 6700, Austria

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Feldbach, A-8330, Austria

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Grieskirchen, 4710, Austria

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Linz, 4020, Austria

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Thalheim, 4600, Austria

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Edegem, 2650, Belgium

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Erpent, 5101, Belgium

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Blumenau, 89030-101, Brazil

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Botucatu, 18.618-686, Brazil

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Florianópolis, 88036-800, Brazil

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Maringá, 87015-000, Brazil

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Porto Alegre, 9002-060, Brazil

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Porto Alegre, 90020-090, Brazil

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Porto Alegre, 90610-000, Brazil

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Porto Alegre, 91350-200, Brazil

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Santo André, 09080-110, Brazil

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São Bernardo do Campo, 09750-420, Brazil

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São Paulo, 05403-000, Brazil

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Sorocaba, 18040-425, Brazil

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Kozloduy, 3320, Bulgaria

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Rousse, 7002, Bulgaria

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Stara Zagora, 6003, Bulgaria

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Calgary, Alberta, T3B 0M3, Canada

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St. John's, NF, A1A 3R5, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Barrie, Ontario, L4M 6M2, Canada

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Sarnia, Ontario, N7T 4X3, Canada

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Stouffville, Ontario, L4A 1H2, Canada

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Toronto, Ontario, M5T 3A9, Canada

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Toronto, Ontario, M9V 4B4, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Québec, Quebec, G1V 4W2, Canada

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Québec, Quebec, G1W 4R4, Canada

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Québec, Quebec, G2J 0C4, Canada

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Saskatoon, Saskatchewan, S7N 0W8, Canada

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Chicoutimi, G7H 5H6, Canada

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Chile, 7770484, Chile

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Curicó, 3341643, Chile

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Quillota, 2260000, Chile

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Santiago, 7500571, Chile

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Santiago, 7500698, Chile

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Santiago, 8380453, Chile

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Talca, 3465584, Chile

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Baotou, 14010, China

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Beijing, 100034, China

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Beijing, 102218, China

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Changsha, 410005, China

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Changsha, 410015, China

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Changsha, 430033, China

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Chengdu, 610041, China

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Chongqing, 402260, China

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Ganzhou, 341099, China

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Guangzhou, 510180, China

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Guiyang, 550002, China

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Haikou, 570311, China

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Hebei, China

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Hefei, 230001, China

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Hohhot, 010017, China

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Hohhot, 10050, China

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Linhai, 317000, China

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Nanchang, 330006, China

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Shanghai, 200002, China

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Shanghai, 200032, China

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Shanghai, 200433, China

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Shenzhen, 518020, China

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Suzhou, 215000, China

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Ürümqi, 830054, China

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Wenzhou, 325027, China

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Wuhan, 430022, China

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Wuhan, 430030, China

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Xi'an, 710061, China

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Yinchuan, 750001, China

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Zhanjiang, 524001, China

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Zhengzhou, 450003, China

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Barranquilla, 80007, Colombia

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Cali, 76001000, Colombia

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Floridablanca, 681004, Colombia

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Medellín, 5001000, Colombia

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Pereira, 660003, Colombia

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Zipaquirá, 200251, Colombia

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Brandýs nad Labem, 250 01, Czechia

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Jindřichův Hradec, 377 01, Czechia

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Ostrava, 708 68, Czechia

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Rokycany, 337 22, Czechia

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Teplice, 415 01, Czechia

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Aalborg, 9000, Denmark

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Hvidovre, 2650, Denmark

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København NV, 2400, Denmark

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Odense C, 5000, Denmark

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Roskilde, 4000, Denmark

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Vejle, 7100, Denmark

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Bamberg, 96049, Germany

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Berlin, 10717, Germany

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Berlin, 12157, Germany

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Berlin, 13187, Germany

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Cologne, 51069, Germany

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Darmstadt, 64283, Germany

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Hamburg, 20354, Germany

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Hanover, D-30173, Germany

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Koblenz, 56068, Germany

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Leipzig, 04103, Germany

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Leipzig, 04207, Germany

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Leipzig, 04357, Germany

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Marburg, 35037, Germany

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Neu-Isenburg, 63263, Germany

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Peine, 31224, Germany

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Potsdam, 14467, Germany

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Rheine, 48431, Germany

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Warendorf, 48231, Germany

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Athens, 11527, Greece

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Exohi Thessaloniki, 57010, Greece

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Ioannina, 45500, Greece

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Thessaloniki, 56429, Greece

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Thessaloniki, 57010, Greece

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Balassagyarmat, 2660, Hungary

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Budapest, 1033, Hungary

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Edelény, 3780, Hungary

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Encs, 3860, Hungary

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Gödöllő, 2100, Hungary

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Hajdúnánás, 4080, Hungary

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Komárom, 2900, Hungary

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Pécs, 7635, Hungary

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Siófok, 8600, Hungary

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Százhalombatta, 2440, Hungary

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Szeged, 6722, Hungary

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Törökbálint, 2045, Hungary

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Calicut, 673 008, India

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Coimbatore, 641028, India

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Guntur, 522001, India

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Hyderabad, 500038, India

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Jaipur, 302039, India

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Thane, 401107, India

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Vijayawada, 520 008, India

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Cona, 44124, Italy

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Genoa, 16132, Italy

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Milan, 20142, Italy

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Milan, 20157, Italy

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Napoli, 80131, Italy

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Reggio Emilia, 42123, Italy

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Roma, 00168, Italy

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Rozzano, 20089, Italy

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Chūōku, 103-0022, Japan

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Chūōku, 104-0031, Japan

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Fukuoka, 814-0180, Japan

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Himeji-shi, 672-8064, Japan

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Hitachi-Naka, 312-0057, Japan

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Joyo-shi, 610-0113, Japan

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Kawachinagano-shi, 586-8521, Japan

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Kishiwada-shi, 596-8501, Japan

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Kobe, 650-0047, Japan

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Kōtoku, 136-0075, Japan

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Kure-shi, 737-0023, Japan

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Matsusaka-shi, 515-8544, Japan

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Mizunami-shi, 509-6134, Japan

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Nagaoka-shi, 940-2085, Japan

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Nagoya, 457-8511, Japan

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Nishinomiya-shi, 663-8501, Japan

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Okayama, 700-8558, Japan

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Osaka, 531-0073, Japan

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Sagamihara-shi, 252-0315, Japan

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Sakaide-shi, 762-8550, Japan

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Sakaishi, 591-8555, Japan

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Seto-shi, 489-8642, Japan

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Shinagawa-ku, 140-8522, Japan

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Shinagawa-ku, 142-8666, Japan

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Toshima-ku, 170-0002, Japan

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Toshima-ku, 170-0003, Japan

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Toshima-ku, 171-0014, Japan

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Toyonaka-shi, 560-8552, Japan

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Ueda-shi, 386-8610, Japan

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Yanagawa-shi, 832-0059, Japan

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Yokohama, 223-0059, Japan

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Guadalajara, 44100, Mexico

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Guadalajara, 44130, Mexico

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Guadalajara, 44200, Mexico

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Mérida, 97070, Mexico

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Veracruz, 91910, Mexico

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Breda, 4818 CK, Netherlands

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Leeuwarden, 8934 AD, Netherlands

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Auckland, 0626, New Zealand

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Auckland, 1051, New Zealand

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Christchurch, 8024, New Zealand

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Dunedin, 9016, New Zealand

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Hamilton, 3204, New Zealand

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Iloilo City, 5000, Philippines

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Los Baños, 4030, Philippines

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Marilao, 3019, Philippines

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Quezon City, 1100, Philippines

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Bialystok, 15-044, Poland

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Chęciny, 26-060, Poland

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Grodzisk Mazowiecki, 05-825, Poland

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Katowice, 40-648, Poland

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Lodz, 90-153, Poland

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Ostrowiec Świętokrzyski, 27-400, Poland

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Poznan, 60-693, Poland

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Poznan, 61-578, Poland

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Proszowice, 32-100, Poland

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Rzeszów, 35-051, Poland

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Warsaw, 02-793, Poland

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Wieluń, 98-300, Poland

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Daegu, 42415, South Korea

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Jeonju, 54907, South Korea

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Seoul, 03312, South Korea

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Seoul, 04401, South Korea

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Seoul, 05030, South Korea

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Seoul, 06591, South Korea

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Wŏnju, 26426, South Korea

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Barcelona, 08017, Spain

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Hospitalet de Llobregat(Barcel, 08907, Spain

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Laredo, 39770, Spain

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Madrid, 28007, Spain

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Madrid, 28046, Spain

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Madrid, 28850, Spain

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Málaga, 29010, Spain

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Santander, 39008, Spain

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Gothenburg, 413 46, Sweden

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Göteborg, 413 45, Sweden

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Lund, 222 22, Sweden

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Malmo, 205 02, Sweden

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Stockholm, 114 46, Sweden

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Adana, 01330, Turkey (Türkiye)

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Istanbul, 34098, Turkey (Türkiye)

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Istanbul, 34844, Turkey (Türkiye)

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Izmir, 35110, Turkey (Türkiye)

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Kocaeli, 41380, Turkey (Türkiye)

Location

Research Site

Mersin, 33343, Turkey (Türkiye)

Location

Research Site

Barnsley, S75 3DL, United Kingdom

Location

Research Site

Birmingham, B9 5SS, United Kingdom

Location

Research Site

Blackpool, FY2 0JH, United Kingdom

Location

Research Site

Bradford, BD9 6RJ, United Kingdom

Location

Research Site

Chertsey, KT16 0PZ, United Kingdom

Location

Research Site

Cottingham, HU16 5JQ, United Kingdom

Location

Research Site

Leicester, LE3 9QP, United Kingdom

Location

Research Site

Manchester, M13 9NQ, United Kingdom

Location

Research Site

Oxford, OX3 7LE, United Kingdom

Location

Research Site

Perth, PH1 1NX, United Kingdom

Location

Research Site

Southampton, SO166YD, United Kingdom

Location

Research Site

Stockton-on-Tees, TS17 6EW, United Kingdom

Location

Research Site

Wishaw, ML2 0DP, United Kingdom

Location

Research Site

Hanoi, 100000, Vietnam

Location

Research Site

Ho Chi Minh City, 700000, Vietnam

Location

Research Site

Hồ Chí Minh, 700000, Vietnam

Location

Related Links

MeSH Terms

Conditions

Pulmonary Disease, Chronic ObstructiveLung Diseases

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Lung Diseases, ObstructiveRespiratory Tract DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Gerard Criner, MD

    Temple University School of Medicine, 3401 North Broad Street, Suite 745 PP, Philadelphia, PA 19140

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 16, 2019

First Posted

August 12, 2019

Study Start

August 26, 2019

Primary Completion

July 28, 2025

Study Completion

July 28, 2025

Last Updated

August 19, 2025

Record last verified: 2025-08

Data Sharing

IPD Sharing
Will share

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment.

Shared Documents
STUDY PROTOCOL, SAP
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles.
Access Criteria
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.
More information

Locations