MedPath

A Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) Versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes (MDS) Participants Who Require Red Blood Cell Transfusions and Are ESA Naïve

Phase 3
Active, not recruiting
Conditions
Myelodysplastic Syndromes
Interventions
Registration Number
NCT03682536
Lead Sponsor
Celgene
Brief Summary

The purpose of this study is to determine the effectiveness of luspatercept (ACE-536) compared to epoetin alfa on red blood cell (RBC) transfusion independence (for at least 12 weeks) with a concurrent hemoglobin increase of at least 1.5 g/dL in participants with anemia due to revised international prognostic scoring system (IPSS-R) very low, low, or intermediate risk myelodysplastic syndromes (MDS) who require RBC transfusions and have never been exposed to erythropoiesis stimulating agent (ESA).

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
363
Inclusion Criteria
  • Documented diagnosis of Myelodysplastic syndromes (MDS) according to WHO 2016 classification that meets revised international prognostic scoring system (IPSS-R) classification of very low, low, or intermediate risk disease, and have < 5% blasts in bone marrow
  • Endogenous serum erythropoietin (sEPO) level of < 500 U/L
  • Requires Red blood cell (RBC) transfusions, as documented by the criteria: Average transfusion requirement of 2 - 6 units/8 weeks of packed red blood cells (pRBCs) confirmed for a minimum of 8 weeks immediately preceding randomization
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2
Exclusion Criteria
  • Clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or hypothyroidism, or any type of known clinically significant bleeding or sequestration or drug induced anemia
  • Known history of diagnosis of Acute myeloid leukemia (AML)
  • Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure (SBP) of ≥ 150 mmHg and/or diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment

Other protocol-defined inclusion/exclusion criteria apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LuspaterceptLuspatercept-
Epoetin alfaEpoetin alfa-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 12 Weeks (84 Days) With a Mean Hemoglobin Increase ≥ 1.5 g/dLWeek 1 through Week 24

Percentage of participants who are RBC transfusion-free for any 12-week period associated with a concurrent mean hemoglobin (Hgb) increase ≥ 1.5 g/dL compared to baseline.

After applying below 14/3-day rule, the baseline Hgb value is defined as the lowest Hgb value from the central, local laboratory, or pre transfusion Hgb from transfusion records that is within 56 days on or prior to the first dose of treatment, or randomization date if participants were not treated.

4/3-day rule: only Hgb values that are at least 14 days after a transfusion may be used unless there is another transfusion within 3 days after the Hgb assessment. If this occurs, that Hgb value will be used despite being \< 14 days after the previous transfusion.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Red Blood Cell Transfusion Independence (RBC-TI) for 24 WeeksWeek 1 through Week 24

Red blood cell transfusion independence (RBC-TI) for 24 weeks is defined as the percentage of participants who did not receive RBC transfusions from Week 1 through Week 24.

Mean Hemoglobin Change Over 24 WeeksWeek 1 through Week 24

Mean hemoglobin (Hgb) change over the 24-week period of Week 1 through Week 24 compared to baseline.

After applying below 14/3-day rule, the baseline Hgb value is defined as the lowest Hgb value from the central, local laboratory, or pre transfusion Hgb from transfusion records that is within 56 days on or prior to the first dose of treatment, or randomization date if participants were not treated.

4/3-day rule: only Hgb values that are at least 14 days after a transfusion may be used unless there is another transfusion within 3 days after the Hgb assessment. If this occurs, that Hgb value will be used despite being \< 14 days after the previous transfusion.

Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 12 Weeks (84 Days)Week 1 through Week 24

Percentage of participants who are RBC transfusion-free over a consecutive 84-day period.

Percentage of Participants Achieving Hematologic Improvement - Erythroid Response (HI-E) Per IWGWeek 1 through Week 24

The percentage of participants meeting the modified HI-E criteria per the International Working Group (IWG) sustained over any consecutive 56-day period in Week 1-24: For participants with baseline red blood cell (RBC) transfusion burden of \>= 4 units/8 weeks, a reduction of at least 4 units RBC transfusion; for participants with baseline RBC transfusion burden of \< 4 units/8 weeks, mean increase of hemoglobin of at least 1.5 g/dL in the absence of transfusions.

The Number of Participants With Adverse Events (AEs)From first dose to 42 days post last dose (Up to approximately an average of 72 weeks and a maximum of 208 weeks)

Treatment-emergent adverse events include adverse events that started on or after the first dose of treatment until 42 days after the last dose of treatment, as well as those serious adverse events (SAEs) made known to the investigator at any time thereafter that are suspected of being related to treatment.

The severity/intensity of AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0). Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.

Time to Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)Week 1 through Week 24

Time from first dose to first onset of transfusion independence ≥ 84 days.

Number of Participants With a Positive Anti-drug Antibody (ADA) TestDay 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose

Number of participants under each ADA positive category. A participant is counted as 'Treatment-Emergent' if there is a positive post-baseline sample while the baseline sample is ADA negative, or there is a positive post-baseline sample with a titer \>= 4-fold of the baseline titer while the baseline sample is ADA positive. A participant is counted as 'Preexisting' if the baseline sample is ADA positive and the participant is not qualified for 'Treatment-Emergent'. If the participant was discontinued from study treatment earlier than one year from the first dose, additional samples will be collected if last ADA is positive.

Baseline is defined as the last value on or before the first dose of study drug.

Time to Hematologic Improvement - Erythroid Response (HI-E)Week 1 through Week 24

Time from first dose to first onset of achieving modified HI-E.

The modified HI-E criteria per the International Working Group (IWG) sustained over any consecutive 56-day period in Week 1-24: For participants with baseline red blood cell (RBC) transfusion burden of \>= 4 units/8 weeks, a reduction of at least 4 units RBC transfusion; for participants with baseline RBC transfusion burden of \< 4 units/8 weeks, mean increase of hemoglobin of at least 1.5 g/dL in the absence of transfusions.

The Number of Red Blood Cell (RBC) Units Transfused Within the First 24 Weeks of TreatmentWeek 1 through Week 24

RBC transfusion burden on treatment is defined as total number of packed red blood cell (pRBC) units transfused within the first 24 weeks of treatment since Week 1.

Time to First Red Blood Cell (RBC) TransfusionWeek 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)

Time to first RBC transfusion is defined as time from Week 1 to first RBC transfusion on treatment. Participants who maintain RBC-TI through the end of the Treatment Period or time of analysis will be censored at EOT visit date, subsequent MDS therapy start date, study discontinuation date, analysis cutoff date or death, whichever occurs first. Median is from un-stratified Kaplan-Meier method.

Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for ≥ 56 Days (8 Weeks)Week 1 through Week 24

Defined as percentage of participants achieving RBC-TI for \>= 56 days during any consecutive 56-day period from Week 1 through Week 24.

Percentage of Participants Achieving Red Blood Cell Transfusion Independence (RBC-TI) for a Consecutive 24-week PeriodWeek 1 through Week 48

Defined as percentage of participants achieving RBC-TI for \>= 168 days during any consecutive 168-day period from Week 1 through Week 48.

Duration of Red Blood Cell Transfusion Independence (RBC-TI) ≥ 12 Weeks (84 Days)Week 1 through End of Treatment (Up to approximately an average of 66 weeks and a maximum of 202 weeks)

Maximum duration of RBC transfusion independence for participants who achieve RBC-TI ≥ 84 days.

The Number of Participants With Acute Myeloid Leukemia (AML) ProgressionFrom randomization to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)

Progression to AML is defined as a diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow.

Median Time to Acute Myeloid Leukemia (AML) ProgressionFrom randomization to first diagnosis of AML up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)

Time to AML progression is defined as the time between randomization and first diagnosis of AML as per WHO classification of ≥ 20% blasts in peripheral blood or bone marrow. Participants with diagnosis of AML will be considered to have had an event. Participants who have not progressed to AML at the time of analysis will be censored at the last assessment date which does not indicate progression to AML estimated by Kaplan-Meier method.

Overall Survival (OS)Randomization to death due to any cause up to 5 years from first dose or 3 years from last dose (whichever occurs later), unless the participant withdraws consent from the study, dies or is lost to follow-up. (Up to approximately 221 weeks)

Time from date of randomization to death due to any cause

Change From Baseline in the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)Baseline and week 24.

The EORTC QLQ-C30 is composed of 30 items that includes a global health status score ranging from: 1-7 as well as scores for 5 functional scales (physical, role, emotional, cognitive and social), 3 symptom scales (fatigue, nausea/vomiting, and pain) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) all ranging from 1-4. Subscale scores are transformed to a 0 to 100 scale. A high score for a functional scale represents a high or healthy level of functioning; a high score for the global health status/health related quality of life (HRQoL) represents a high overall HRQoL; but a high score for a symptom scale represents a high level of symptomatology or problems. Baseline is defined as the last value on or before the first dose of study drug.

Area Under the Concentration-time Curve [AUC]Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose
Maximum Plasma Concentration of Drug [Cmax]Day 1 on week 4, 10, 16, 22, and every 12 weeks (±14 days) from the 24-Week MDS Assessment visit for up to one year from the first dose
Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Version 4 (FACT-An)Baseline, Day 1 on weeks 7,13,19, and 24.

The Functional Assessment of Cancer Therapy - Anemia (FACT-An) questionnaire includes 47 items rating on a 5-point Likert scale from 0 (not at all) to 4 (very much) (so that 0 is considered worse quality of life and 4 is good response) on five primary subscales:

* Physical well-being (sum of 7 items, score range from 0-28)

* Social/Family well-being (sum of 7 items, score range from 0-28)

* Emotional well-being (sum of 6 items, score range from 0-24)

* Functional well-being (sum of 7 items, score range from 0-28)

* Anemia-related symptoms (sum of 20 items, score range from 0-80)

A total score for the FACT-An can be calculated by summing the five primary subscales with a score range from 0-188. Higher scores representing better quality of life. Baseline is defined as the last value on or before the first dose of study drug.

Trial Locations

Locations (226)

Local Institution - 114

🇺🇸

Salt Lake City, Utah, United States

Local Institution - 107

🇺🇸

Berkeley, California, United States

Local Institution - 115

🇺🇸

San Diego, California, United States

Local Institution - 101

🇺🇸

Whittier, California, United States

Local Institution - 104

🇺🇸

New Haven, Connecticut, United States

Local Institution - 136

🇺🇸

Washington, District of Columbia, United States

Local Institution - 119

🇺🇸

Hudson, Florida, United States

Local Institution - 120

🇺🇸

Saint Petersburg, Florida, United States

Local Institution - 122

🇺🇸

Tallahassee, Florida, United States

Local Institution - 108

🇺🇸

Tampa, Florida, United States

Local Institution - 118

🇺🇸

West Palm Beach, Florida, United States

Local Institution - 102

🇺🇸

Paducah, Kentucky, United States

Local Institution - 123

🇺🇸

Bethesda, Maryland, United States

Local Institution - 117

🇺🇸

Kansas City, Missouri, United States

Local Institution - 134

🇺🇸

East Brunswick, New Jersey, United States

Local Institution - 113

🇺🇸

Hackensack, New Jersey, United States

Local Institution - 105

🇺🇸

Greenville, North Carolina, United States

Local Institution - 131

🇺🇸

Portland, Oregon, United States

Univ of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Local Institution - 111

🇺🇸

Rock Hill, South Carolina, United States

Tennessee Oncology

🇺🇸

Nashville, Tennessee, United States

Baylor University Medical Center

🇺🇸

Dallas, Texas, United States

Local Institution - 109

🇺🇸

Houston, Texas, United States

Local Institution - 132

🇺🇸

Charlottesville, Virginia, United States

Local Institution - 127

🇺🇸

Chesapeake, Virginia, United States

Local Institution - 206

🇦🇺

Albury, New South Wales, Australia

Local Institution - 213

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Blacktown, New South Wales, Australia

Local Institution - 200

🇦🇺

Concord, New South Wales, Australia

Local Institution - 215

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Kogarah, New South Wales, Australia

Local Institution - 211

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Nowra, New South Wales, Australia

Local Institution - 210

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Waratah, New South Wales, Australia

Local Institution - 207

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Wollongong, New South Wales, Australia

Local Institution - 208

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Auchenflower, Queensland, Australia

Local Institution - 202

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Adelaide, South Australia, Australia

Local Institution - 204

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Clayton, Victoria, Australia

Local Institution - 203

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Malvern, Victoria, Australia

Local Institution - 209

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Melbourne, Victoria, Australia

Local Institution - 205

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West Perth, Western Australia, Australia

Local Institution - 212

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Randwick, Australia

Local Institution - 442

🇦🇹

Linz, Austria

Local Institution - 441

🇦🇹

Vienna, Austria

Local Institution - 475

🇧🇪

Antwerpen, Belgium

Local Institution - 471

🇧🇪

Brasschaat, Belgium

Local Institution - 474

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Brussels, Belgium

Local Institution - 472

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Charleroi, Belgium

Local Institution - 473

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Kortrijk, Belgium

Local Institution - 470

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Leuven, Belgium

Local Institution - 476

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Roeselare, Belgium

Local Institution - 147

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Calgary, Alberta, Canada

Local Institution - 145

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Edmonton, Alberta, Canada

Local Institution - 142

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Hamilton, Ontario, Canada

Local Institution - 140

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Ottawa, Ontario, Canada

Local Institution - 141

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Toronto, Ontario, Canada

Local Institution - 144

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Montreal, Quebec, Canada

Local Institution - 148

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Montreal, Quebec, Canada

Local Institution - 151

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Saskatoon, Saskatchewan, Canada

Local Institution - 152

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Sherbrooke, Canada

Local Institution - 560

🇨🇿

Hradec Kralove, Czechia

Local Institution - 564

🇨🇿

Ostrava-Poruba, Czechia

Local Institution - 563

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Prague 10, Czechia

Local Institution - 562

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Praha 2, Czechia

Local Institution - 561

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Praha, Czechia

Local Institution - 317

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Angers, France

Local Institution - 312

🇫🇷

Bayonne, France

Local Institution - 311

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Caen Cedex 9, France

Local Institution - 306

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La Tronche, France

Local Institution - 305

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Le Mans, France

Local Institution - 309

🇫🇷

Lille, France

Local Institution - 303

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Limoges Cedex, France

Local Institution - 307

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Nantes Cedex 01, France

Local Institution - 301

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Nice Cedex 3, France

Local Institution - 302

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Paris, France

Local Institution - 313

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Paris, France

Local Institution - 308

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Pessac, France

Local Institution - 315

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Pierre Bénite, France

Local Institution - 316

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Poitiers, France

Local Institution - 314

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Strasbourg, France

Local Institution - 300

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Toulouse, France

Local Institution - 310

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Tours cedex, France

Local Institution - 304

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Vandoeuvre les Nancy, France

Local Institution - 422

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Baden-Warttemberg, Germany

Local Institution - 424

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Berlin, Germany

Local Institution - 426

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Dresden, Germany

Local Institution - 429

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Duisburg, Germany

Local Institution - 420

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Dusseldorf, Germany

Local Institution - 431

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Hamburg, Germany

Local Institution - 435

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Keil, Germany

Local Institution - 423

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Koblenz, Germany

Local Institution - 428

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Köln, Germany

Local Institution - 430

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Leipzig, Germany

Local Institution - 436

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Mannheim, Germany

Local Institution - 421

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Munchen, Germany

Local Institution - 425

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Winnenden, Germany

Local Institution - 427

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Würzburg, Germany

Local Institution - 389

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Heraklion, Irakleio, Greece

Local Institution - 396

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Alexandroupolis, Greece

Local Institution - 397

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Athens, Greece

Local Institution - 391

🇬🇷

Athens, Greece

Local Institution - 392

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Athens, Greece

Local Institution - 395

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Athina, Greece

Local Institution - 398

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Patras, Greece

Local Institution - 393

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Rio Patras, Greece

Local Institution - 399

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Thessaloniki, Greece

Local Institution - 390

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Thessaloniki, Greece

Local Institution - 535

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Budapest, Hungary

Local Institution - 534

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Debrecen, Hungary

Local Institution - 536

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Nyiregyhaza, Hungary

Local Institution - 386

🇮🇱

Haifa, Israel

Local Institution - 383

🇮🇱

Jerusalem, Israel

Local Institution - 384

🇮🇱

Jerusalem, Israel

Local Institution - 381

🇮🇱

Kfar-Saba, Israel

Local Institution - 385

🇮🇱

Nahariya, Israel

Local Institution - 382

🇮🇱

Tel Aviv, Israel

Local Institution - 380

🇮🇱

Zerifin, Israel

Local Institution - 331

🇮🇹

Orbassano, TO, Italy

Local Institution - 324

🇮🇹

Bologna, Italy

Local Institution - 327

🇮🇹

Firenze, Italy

Local Institution - 330

🇮🇹

Meldola, Italy

Local Institution - 321

🇮🇹

Milano, Italy

Local Institution - 329

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Padova, Italy

Local Institution - 326

🇮🇹

Reggio Di Calabria, Italy

Local Institution - 328

🇮🇹

Roma, Italy

Local Institution - 332

🇮🇹

Roma, Italy

Local Institution - 325

🇮🇹

Rome, Italy

Local Institution - 323

🇮🇹

Rozzano, Italy

Local Institution - 322

🇮🇹

Udine, Italy

Local Institution - 238

🇯🇵

Matsuyama, Ehime, Japan

Local Institution - 244

🇯🇵

Nagasaki-shi, Nagasaki, Japan

Local Institution - 236

🇯🇵

Osakasayama, Osaka, Japan

Local Institution - 247

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Amagasaki-Shi, Japan

Local Institution - 249

🇯🇵

Fujisawa-Shi, Japan

Local Institution - 234

🇯🇵

Fukuoka, Japan

Local Institution - 237

🇯🇵

Hitachi, Ibaraki, Japan

Local Institution - 231

🇯🇵

Kamogawa, Japan

Local Institution - 248

🇯🇵

Kitakyushu-Shi, Japan

Local Institution - 270

🇯🇵

Nagaoka-Shi, Japan

Local Institution - 243

🇯🇵

Nagoya-shi, Japan

Local Institution - 241

🇯🇵

Ogaki, Japan

Local Institution - 235

🇯🇵

Okayama, Japan

Local Institution - 242

🇯🇵

Osaka, Japan

Local Institution - 233

🇯🇵

Sagamihara, Japan

Local Institution - 246

🇯🇵

Sapporo-shi, Japan

Local Institution - 239

🇯🇵

Sendai, Japan

Local Institution - 232

🇯🇵

Shibuya-ku, Japan

Local Institution - 245

🇯🇵

Shimotsuga-gun, Japan

Local Institution - 230

🇯🇵

Shinagawa-ku, Tokyo, Japan

Local Institution - 251

🇰🇷

Busan, Korea, Republic of

Local Institution - 257

🇰🇷

Daegu, Korea, Republic of

Local Institution - 250

🇰🇷

Hwasun-Gun, Korea, Republic of

Local Institution - 253

🇰🇷

Seongnamsi, Korea, Republic of

Local Institution - 252

🇰🇷

Seoul, Korea, Republic of

Local Institution - 256

🇰🇷

Seoul, Korea, Republic of

Local Institution - 255

🇰🇷

Seoul, Korea, Republic of

Local Institution - 254

🇰🇷

Seoul, Korea, Republic of

Local Institution - 540

🇱🇹

Kaunas, Lithuania

Local Institution - 541

🇱🇹

Vilnius, Lithuania

Local Institution - 462

🇳🇱

Amsterdam, Netherlands

Local Institution - 461

🇳🇱

Den Haag, Netherlands

Local Institution - 464

🇳🇱

Nijmegen, Netherlands

Local Institution - 460

🇳🇱

Rotterdam, Netherlands

Local Institution - 463

🇳🇱

Sittard-Geleen, Netherlands

Local Institution - 570

🇵🇱

Lodz, Lódzkie, Poland

Local Institution - 575

🇵🇱

Gdansk, Poland

Local Institution - 572

🇵🇱

Lubin, Poland

Local Institution - 576

🇵🇱

Poznan, Poland

Local Institution - 573

🇵🇱

Rzwszow, Poland

Local Institution - 579

🇵🇱

Slupsk, Poland

Local Institution - 578

🇵🇱

Walbrzych, Poland

Local Institution - 577

🇵🇱

Wroclaw, Poland

Local Institution - 571

🇵🇱

Wroclaw, Poland

Local Institution - 373

🇵🇹

Beja, Portugal

Local Institution - 371

🇵🇹

Braga, Portugal

Local Institution - 372

🇵🇹

Lisboa, Portugal

Local Institution - 370

🇵🇹

Porto, Portugal

Local Institution - 374

🇵🇹

Setubal, Portugal

Local Institution - 511

🇷🇺

Kaluga, Russian Federation

Local Institution - 505

🇷🇺

Kirov, Russian Federation

Local Institution - 509

🇷🇺

Krasnoyarsk, Russian Federation

Local Institution - 504

🇷🇺

Moscow, Russian Federation

Local Institution - 507

🇷🇺

Moscow, Russian Federation

Local Institution - 500

🇷🇺

Moscow, Russian Federation

Local Institution - 503

🇷🇺

Moscow, Russian Federation

Local Institution - 508

🇷🇺

Saratov, Russian Federation

Local Institution - 506

🇷🇺

St Petersburg, Russian Federation

Local Institution - 510

🇷🇺

St. Petersburg, Russian Federation

Local Institution - 502

🇷🇺

Tula, Russian Federation

Local Institution - 358

🇪🇸

Barcelona, Spain

Local Institution - 350

🇪🇸

Barcelona, Spain

Local Institution - 354

🇪🇸

Granada, Spain

Local Institution - 352

🇪🇸

Madrid, Spain

Local Institution - 355

🇪🇸

Madrid, Spain

Local Institution - 353

🇪🇸

Malaga, Spain

Local Institution - 361

🇪🇸

Murcia, Spain

Local Institution - 356

🇪🇸

Ourense, Spain

Local Institution - 363

🇪🇸

Oviedo, Spain

Local Institution - 362

🇪🇸

Palma de Mallorca, Spain

Local Institution - 351

🇪🇸

Salamanca, Spain

Local Institution - 360

🇪🇸

Seville, Spain

Local Institution - 357

🇪🇸

Valencia, Spain

Local Institution - 359

🇪🇸

Valencia, Spain

Local Institution - 550

🇸🇪

Goteborg, Sweden

Local Institution - 552

🇸🇪

Lund, Sweden

Local Institution - 551

🇸🇪

Stockholm, Sweden

Local Institution - 450

🇨🇭

Bern, Switzerland

Local Institution - 452

🇨🇭

Luzern 16, Switzerland

Local Institution - 451

🇨🇭

Winterthur, Switzerland

Local Institution - 220

🇨🇳

Changhua City, Changhua, Taiwan

Local Institution - 222

🇨🇳

Niaosong District Kaohsiung City, Taiwan

Local Institution - 223

🇨🇳

Taichung City, Taiwan

Local Institution - 224

🇨🇳

Taichung, Taiwan

Local Institution - 221

🇨🇳

Taipei, Taiwan

Local Institution - 342

🇹🇷

Ankara, Turkey

Local Institution - 340

🇹🇷

Manisa, Turkey

Local Institution - 343

🇹🇷

Trabzon, Turkey

Local Institution - 526

🇺🇦

Cherkassy, Ukraine

Local Institution - 525

🇺🇦

Dnipro, Ukraine

Local Institution - 522

🇺🇦

Kyiv, Ukraine

Local Institution - 520

🇺🇦

Lvov, Ukraine

Local Institution - 523

🇺🇦

Mykolaiv, Ukraine

Local Institution - 521

🇺🇦

Ternopil, Ukraine

Local Institution - 401

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Aberdeen, United Kingdom

Local Institution - 403

🇬🇧

Bournemouth, United Kingdom

Local Institution - 405

🇬🇧

Headington, Oxford, United Kingdom

Local Institution - 407

🇬🇧

Lincoln, United Kingdom

Local Institution - 404

🇬🇧

London, United Kingdom

Local Institution - 400

🇬🇧

Manchester, United Kingdom

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