Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations
NCT ID: NCT04053634
Last Updated: 2025-08-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
689 participants
INTERVENTIONAL
2019-08-26
2025-07-28
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
TRIPLE
Study Groups
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Benralizumab
Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks
Benralizumab
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.
Placebo
Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks
Placebo
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.
Interventions
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Benralizumab
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.
Placebo
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.
Eligibility Criteria
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Inclusion Criteria
2. Age 40 to 85 years
3. Male and/or female.
4. Current or former smoker with a tobacco history of ≥10 pack-years.
5. History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC\<0.70 and FEV1 ≤65% of predicted normal value.
6. Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment.
1. Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization.
2. Hospitalization is defined as an inpatient admission ≥24 hours
3. Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD.
4. At least one qualifying COPD exacerbation should occur while on stable uninterrupted triple therapy prior to enrolment.
7. Documented use of triple (ICS/LABA/LAMA) background therapy for COPD for ≥3 months immediately prior to enrollment.
1. 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.
2. ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily.
3. Total cumulative duration of not being on double or triple background therapy must not exceed 2 months.
4. Stable therapy/doses for the last 3 months prior to randomization.
8. Blood eosinophil count ≥300/μL at screening and documented historical eosinophil count of ≥150/μL within 52 weeks of enrollment (or repeated testing during run-in).
9. CAT total score ≥15 at Visit 1.
10. Negative pregnancy test for females of childbearing potential (WOCBP) at Visit 1.
11. Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control from enrollment throughout the study and within 12 weeks after last dose of IP.
Women not of childbearing potential are defined as women who are either permanently sterilized or postmenopausal (confirmed by FSH test for women \<50 years).
Exclusion Criteria
2. 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.
3. 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.
4. Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
5. Any unstable disorder that could affect patient safety, study findings or the patient's ability to complete the study.
6. 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.
7. Cor pulmonale and/or right ventricular failure.
8. Long-term treatment with oxygen \>4.0 L/min and/or oxyhemoglobin saturation \<89% while breathing supplemental oxygen.
9. Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed.
10. Known immunodeficiency disorder, including positive HIV-1/2 testing.
11. 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.
12. ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during the run-in period.
13. Helminth parasitic infection within 24 weeks prior to enrollment, not treated or failed to respond to standard of care therapy.
14. Alcohol or drug abuse within the past year, which may compromise the study data.
15. 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.
16. Evidence of active tuberculosis, as judged by investigator. Patients with a recent (within 2 years) first-time or newly positive PPD or Quantiferon test need to complete an appropriate course of treatment before enrollment. Evaluation will be according to the local standard of care.
17. Participation, or planned participation, in intensive COPD rehabilitation program (maintenance phase of a rehabilitation is allowed).
18. History of surgical or endoscopic lung volume reduction within the 6 months prior to enrollment. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
19. Scheduled major surgical procedure during the study. Minor elective procedures are allowed.
20. History of anaphylaxis to any biologic therapy or vaccine.
21. Receipt of blood products or immunoglobulins within 30 days prior to randomization.
22. Receipt of marketed or investigational biologic product within 4 months or 5 half-lives prior to randomization, whichever is longer. Exception: Patients on stable therapy for 3 months before randomization who intend to stay on treatment throughout the study with marketed biologic products that are not likely to interfere with the safety assessment and/or efficacy of benralizumab, for example, for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, cardiovascular, or metabolic diseases, can participate in the study.
23. Receipt of live attenuated vaccines 30 days prior to randomization.
24. Chronic use of immunosuppressive medication or expected need for chronic use during the study.
25. Chronic use of antibiotics if duration of treatment is \<9 months prior to randomization. Chronic macrolide or other antibiotic therapy is allowed provided the patient has been on stable dose/regimen for ≥9 months prior to randomization and has had ≥2 COPD exacerbations while on stable therapy.
26. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to enrollment.
27. Receipt of benralizumab within 12 months prior to enrollment.
28. Known history of allergy or reaction to any component of the IP formulation.
40 Years
85 Years
ALL
No
Sponsors
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AstraZeneca
INDUSTRY
Responsible Party
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Principal Investigators
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Gerard Criner, MD
Role: PRINCIPAL_INVESTIGATOR
Temple University School of Medicine, 3401 North Broad Street, Suite 745 PP, Philadelphia, PA 19140
Locations
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Surprise, Arizona, United States
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Little Rock, Arkansas, United States
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Los Angeles, California, United States
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Los Angeles, California, United States
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Newport Beach, California, United States
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Northridge, California, United States
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Palm Springs, California, United States
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Westminster, California, United States
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Stamford, Connecticut, United States
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Clearwater, Florida, United States
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Daytona Beach, Florida, United States
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Edgewater, Florida, United States
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Jacksonville, Florida, United States
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Jacksonville, Florida, United States
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Kissimmee, Florida, United States
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Kissimmee, Florida, United States
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Leesburg, Florida, United States
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Miami, Florida, United States
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Orlando, Florida, United States
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Pensacola, Florida, United States
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St. Petersburg, Florida, United States
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Tampa, Florida, United States
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Winter Park, Florida, United States
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Lawrenceville, Georgia, United States
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Rincon, Georgia, United States
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Chicago, Illinois, United States
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O'Fallon, Illinois, United States
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Peoria, Illinois, United States
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Michigan City, Indiana, United States
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Iowa City, Iowa, United States
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Kansas City, Kansas, United States
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Georgetown, Kentucky, United States
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Baltimore, Maryland, United States
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Columbia, Maryland, United States
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Boston, Massachusetts, United States
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North Dartmouth, Massachusetts, United States
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Farmington Hills, Michigan, United States
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Lincoln, Nebraska, United States
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Omaha, Nebraska, United States
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Toms River, New Jersey, United States
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Buffalo, New York, United States
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New Windsor, 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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Charlotte, North Carolina, United States
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Elizabeth City, North Carolina, United States
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Gastonia, 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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Wilmington, North Carolina, United States
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Winston-Salem, North Carolina, United States
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Cleveland, Ohio, United States
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Columbus, Ohio, United States
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Oklahoma City, Oklahoma, United States
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Medford, Oregon, United States
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DuBois, Pennsylvania, United States
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Philadelphia, Pennsylvania, United States
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Pittsburgh, Pennsylvania, United States
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Smithfield, Pennsylvania, United States
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Mt. Pleasant, South Carolina, United States
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North Charleston, South Carolina, United States
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Rock Hill, South Carolina, United States
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Rapid City, South Dakota, United States
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Chattanooga, Tennessee, United States
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Franklin, Tennessee, United States
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Hendersonville, Tennessee, United States
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Johnson City, Tennessee, United States
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Amarillo, Texas, United States
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Amarillo, Texas, United States
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Cypress, Texas, United States
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Dallas, Texas, United States
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Fort Worth, Texas, United States
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Houston, Texas, United States
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Kerrville, Texas, United States
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San Antonio, Texas, United States
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Tomball, Texas, United States
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Salt Lake City, Utah, United States
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Abingdon, Virginia, United States
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Salem, Virginia, United States
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Williamsburg, Virginia, United States
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Everett, Washington, United States
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Spokane, Washington, United States
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Morgantown, West Virginia, United States
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Cudahy, Wisconsin, United States
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Buenos Aires, , 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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Córdoba, , Argentina
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Florida, , Argentina
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Mar del Plata, , Argentina
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Mendoza, , 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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Caringbah, , Australia
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Melbourne, , Australia
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South Brisbane, , Australia
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Southport, , Australia
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Spearwood, , Australia
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Bad Ischl, , Austria
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Bludenz, , Austria
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Feldbach, , Austria
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Grieskirchen, , Austria
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Linz, , Austria
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Thalheim, , Austria
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Edegem, , Belgium
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Erpent, , Belgium
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Blumenau, , Brazil
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Botucatu, , Brazil
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Maringá, , 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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Santo André, , Brazil
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São Bernardo do Campo, , Brazil
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São Paulo, , Brazil
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Sorocaba, , Brazil
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Kozloduy, , Bulgaria
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Rousse, , Bulgaria
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Stara Zagora, , Bulgaria
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Calgary, Alberta, Canada
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St. John's, NF, Canada
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Ajax, Ontario, Canada
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Barrie, Ontario, Canada
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Sarnia, Ontario, Canada
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Stouffville, Ontario, Canada
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Toronto, Ontario, Canada
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Toronto, Ontario, Canada
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Montreal, Quebec, Canada
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Québec, Quebec, Canada
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Québec, Quebec, Canada
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Québec, Quebec, Canada
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Saskatoon, Saskatchewan, Canada
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Chicoutimi, , Canada
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Chile, , Chile
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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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Santiago, , Chile
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Talca, , Chile
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Baotou, , China
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Beijing, , China
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Beijing, , China
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Changsha, , China
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Changsha, , China
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Changsha, , China
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Chengdu, , China
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Chongqing, , China
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Ganzhou, , China
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Guangzhou, , China
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Guiyang, , China
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Haikou, , China
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Hebei, , China
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Hefei, , China
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Hohhot, , China
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Hohhot, , China
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Linhai, , China
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Nanchang, , China
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Shanghai, , China
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Shanghai, , China
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Shanghai, , China
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Shenzhen, , China
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Suzhou, , China
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Ürümqi, , China
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Wenzhou, , China
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Wuhan, , China
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Wuhan, , China
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Xi'an, , China
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Yinchuan, , China
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Zhanjiang, , China
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Zhengzhou, , China
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Barranquilla, , Colombia
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Cali, , Colombia
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Floridablanca, , Colombia
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Medellín, , Colombia
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Pereira, , Colombia
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Zipaquirá, , Colombia
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Brandýs nad Labem, , Czechia
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Jindřichův Hradec, , Czechia
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Ostrava, , Czechia
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Rokycany, , Czechia
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Teplice, , Czechia
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Aalborg, , Denmark
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Hvidovre, , Denmark
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København NV, , Denmark
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Odense C, , Denmark
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Roskilde, , Denmark
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Vejle, , Denmark
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Bamberg, , Germany
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Berlin, , Germany
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Berlin, , Germany
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Berlin, , Germany
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Cologne, , Germany
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Darmstadt, , Germany
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Hamburg, , Germany
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Hanover, , Germany
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Koblenz, , Germany
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Leipzig, , Germany
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Leipzig, , Germany
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Leipzig, , Germany
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Marburg, , Germany
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Neu-Isenburg, , Germany
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Peine, , Germany
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Potsdam, , Germany
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Rheine, , Germany
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Warendorf, , Germany
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Athens, , Greece
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Exohi Thessaloniki, , Greece
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Ioannina, , Greece
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Thessaloniki, , Greece
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Thessaloniki, , Greece
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Balassagyarmat, , Hungary
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Budapest, , Hungary
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Edelény, , Hungary
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Encs, , Hungary
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Gödöllő, , Hungary
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Hajdúnánás, , Hungary
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Komárom, , Hungary
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Pécs, , Hungary
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Siófok, , Hungary
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Százhalombatta, , Hungary
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Szeged, , Hungary
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Törökbálint, , Hungary
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Calicut, , India
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Coimbatore, , India
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Guntur, , India
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Hyderabad, , India
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Jaipur, , India
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Thāne, , India
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Vijayawada, , India
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Cona, , Italy
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Genoa, , Italy
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Milan, , Italy
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Milan, , Italy
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Napoli, , Italy
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Reggio Emilia, , Italy
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Roma, , Italy
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Rozzano, , Italy
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Chūōku, , Japan
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Chūōku, , Japan
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Fukuoka, , Japan
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Himeji-shi, , Japan
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Hitachi-Naka, , Japan
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Joyo-shi, , Japan
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Kawachinagano-shi, , Japan
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Kishiwada-shi, , Japan
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Kobe, , Japan
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Kōtoku, , Japan
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Kure-shi, , Japan
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Matsusaka-shi, , Japan
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Mizunami-shi, , Japan
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Nagaoka-shi, , Japan
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Nagoya, , Japan
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Nishinomiya-shi, , Japan
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Okayama, , Japan
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Osaka, , Japan
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Sagamihara-shi, , Japan
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Sakaide-shi, , Japan
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Sakaishi, , Japan
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Seto-shi, , Japan
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Shinagawa-ku, , Japan
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Shinagawa-ku, , Japan
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Toshima-ku, , Japan
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Toshima-ku, , Japan
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Toshima-ku, , Japan
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Toyonaka-shi, , Japan
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Ueda-shi, , Japan
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Yanagawa-shi, , Japan
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Yokohama, , Japan
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Guadalajara, , Mexico
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Guadalajara, , Mexico
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Guadalajara, , Mexico
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Mérida, , Mexico
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Veracruz, , Mexico
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Breda, , Netherlands
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Leeuwarden, , Netherlands
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Auckland, , New Zealand
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Auckland, , New Zealand
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Christchurch, , New Zealand
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Dunedin, , New Zealand
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Hamilton, , New Zealand
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Iloilo City, , Philippines
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Los Baños, , Philippines
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Marilao, , Philippines
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Quezon City, , Philippines
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Bialystok, , Poland
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Chęciny, , Poland
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Grodzisk Mazowiecki, , Poland
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Katowice, , Poland
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Lodz, , Poland
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Ostrowiec Świętokrzyski, , Poland
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Poznan, , Poland
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Poznan, , Poland
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Proszowice, , Poland
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Rzeszów, , Poland
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Warsaw, , Poland
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Wieluń, , Poland
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Daegu, , South Korea
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Jeonju, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Seoul, , South Korea
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Wŏnju, , South Korea
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Barcelona, , Spain
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Hospitalet de Llobregat(Barcel, , Spain
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Laredo, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Madrid, , Spain
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Málaga, , Spain
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Santander, , Spain
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Gothenburg, , Sweden
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Göteborg, , Sweden
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Lund, , Sweden
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Malmo, , Sweden
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Stockholm, , Sweden
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Adana, , 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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Kocaeli, , Turkey (Türkiye)
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Mersin, , Turkey (Türkiye)
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Barnsley, , United Kingdom
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Birmingham, , United Kingdom
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Blackpool, , United Kingdom
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Bradford, , United Kingdom
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Chertsey, , United Kingdom
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Cottingham, , United Kingdom
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Leicester, , United Kingdom
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Manchester, , United Kingdom
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Oxford, , United Kingdom
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Perth, , United Kingdom
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Southampton, , United Kingdom
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Stockton-on-Tees, , United Kingdom
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Wishaw, , United Kingdom
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Hanoi, , Vietnam
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Ho Chi Minh City, , Vietnam
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Hồ Chí Minh, , Vietnam
Countries
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Related Links
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Other Identifiers
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2019-001800-39
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
D3251C00014
Identifier Type: -
Identifier Source: org_study_id
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