A Multi-Site, Open-Label Extension Trial of Oral RPC1063 in Relapsing Multiple Sclerosis
- Registration Number
- NCT02576717
- Lead Sponsor
- Celgene
- Brief Summary
The purpose of the trial is to determine the safety and efficacy of RPC1063 in patients with relapsing multiple sclerosis.
- Detailed Description
The trial is an open label extension study. Eligible patients from the RPC01-201, RPC01-301, and RPC01-1001 trials diagnosed with relapsing Multiple Sclerosis (RMS) will be enrolled to receive study drug until the end of the trial or until the Sponsor discontinues the development program.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2494
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1 mg RPC1063 (Ozanimod) oral capsule RPC1063 1 mg RPC1063 (Ozanimod) oral capsule daily
- Primary Outcome Measures
Name Time Method Number of Participants Experiencing Adverse Events (AEs) From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months) An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
Number of Participants Experiencing Serious Adverse Events (SAEs) From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months) A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose results in death, is life-threatening (defined as an event in which the subject was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe), requires inpatient hospitalization or causes prolongation of existing hospitalization.
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months) An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
Number of Participants Experiencing Adverse Events (AEs) Leading to Withdrawal From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months) An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
Number of Participants Experiencing Adverse Events (AEs) of Special Interest From first dose to 90-days post last dose (an average of 65 months up to a max of 85 months) An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporarily associated with the use of medicinal product, whether or not considered related to the investigational medicinal product.
Number of Participants With Abnormalities in Blood Absolute Lymphocyte Count (ALC) From first dose up until last dose of study treatment (up to approximately 82 months) An absolute lymphocyte count (ALC) is a part of a blood test that measures the number of lymphocytes, a type of white blood cell, in the blood. Lymphocytes help fight infections and diseases. Reductions in ALC levels for participants in this study is expected and is a primary pharmacodynamic effect of RPC1063.
LLN = Lower limit of normalNumber of Participants With Abnormalities in White Blood Cell Count (WBC) From first dose up until last dose of study treatment (up to approximately 82 months) A white blood cell count is a part of a blood test that measures the number of white blood cells in the blood. White blood cells help fight infections and diseases.
LLN = Lower limit of normalNumber of Participants With Abnormalities in Blood Absolute Neutrophil Count (ANC) From first dose up until last dose of study treatment (up to approximately 82 months) An absolute neutrophil count is a part of a blood test that measures the number of neutrophils, a type of white blood cell, in the blood. Neutrophils help fight infections and diseases.
Number of Participants With Abnormalities in Specific Liver Function Tests From first dose up until last dose of study treatment (up to approximately 82 months) The number of participants with laboratory abnormalities in specific liver tests above ULN by category. ULN = Upper Limit of Normal
Number of Participants With Electrocardiogram (ECG) Result Abnormalities From first dose to 28-days post last dose (an average of 63 months up to a max of 83 months) An electrocardiogram (ECG) measures electrical activity of the heart to detect cardiac problems.
Number of Participants With Clinically Relevant Abnormalities in Vital Signs At baseline and 60 months after first dose of study therapy Vital signs included body temperature, sitting heart rate/pulse (HR), sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP).
Baseline refers to assessments made on or before the first day participants received study treatment.Number of Participants With Physical Examination Abnormalities At baseline and every 12 months thereafter up until 84 months post first dose. The number of participants with abnormal physical examination results. The assessments included abdominal, extremity, head, heart, lungs, neck, neurological non-MS, other and skin assessments.
Baseline refers to assessments made on or before the first day participants received study treatment.Number of Participants Self-Identifying Suicidality by Columbia-Suicide Severity Rating Scale (C-SSRS) At baseline and every 3 months thereafter up until 78 months post first dose. The Columbia-Suicide Severity Rating Scale (C-SSRS) is a unique suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs.
Results are displayed as the number of participants who answered "Yes" to at least one of the 10 questions in the suicidal ideation or suicidal behavior section.
Ideation from 1 (wishing to be dead) - 5 (Active suicidal ideation with specific plan and intent) Behavior from 6 (Preparatory acts or behavior) - 10 (Completed suicide). Baseline refers to assessments made on or before the first day participants received study treatment.Number of Participants With Changes in Suicidality From Last Day on Treatment Per the Columbia-Suicide Severity Rating Scale (C-SSRS) 1, 4, 7, 14, 21, 28, and 90 days post last dose. The Columbia-Suicide Severity Rating Scale (C-SSRS) is a unique suicide risk assessment tool that supports suicide risk assessment through a series of simple, plain-language questions. The answers help users identify whether someone is at risk for suicide, assess the severity and immediacy of that risk, and gauge the level of support that the person needs.
Results are displayed as the number of participants who answered "Yes" to at least one of the 10 questions in the suicidal ideation or suicidal behavior section.
Ideation from 1 (wishing to be dead) - 5 (Active suicidal ideation with specific plan and intent) Behavior from 6 (Preparatory acts or behavior) - 10 (Completed suicide).Change in Physician's Withdrawal Checklist (PWC-20) Total Score From Last Day on Treatment 1, 4, 7, 14, 21, and 90 days post last dose. The PWC-20 is a rater-administered 20-item scale to assess signs and symptoms of withdrawal. Twenty items are rated on a 4-point scale as not present (0 points), mild (1 point), moderate (2 points), or severe (3 points). The points from all items are calculated as a total score. Higher scores indicate more severe withdrawal symptoms.
Change in Hospital Anxiety and Depression Scale (HADS) Score From Last Day on Treatment 1, 4, 7, 14, 21, and 90 days post last dose. The HADS is a validated patient reported outcome for assessing anxiety and depression. It consists of 14 items in total, 7 items related to anxiety and 7 items related to depression. For each item patients select a statement (valued at 0 to 3 points) that closest matches their own feeling over the past week. Separate total scores for anxiety and depression are derived by adding up points. Total scores can range from 0 to 21 points. Higher scores indicate more severe anxiety and depression and scores of 8 to 10 are generally considered indicative of borderline anxiety/depression disorders and scores of 11 and higher are generally considered indicative of anxiety/depression disorders.
Changes in Epworth Sleepiness Scale (ESS) Score From Last Day on Treatment 1, 4, 7, 14, 21, and 90 days post last dose. The ESS is a validated self administered questionnaire with 8 questions. Respondents rate on a 4-point scale (0 to 3) their chances of dozing off or falling asleep while engaged in 8 different activities. The ESS score is the sum of 8 item scores and can range from 0 to 24 points. Higher scores indicate more daytime sleepiness.
Changes in Vital Sign Values From Last Day on Treatment 1, 4, 7, 14, 21, 28, and 90 days post last dose. Vital signs included sitting systolic blood pressure (SBP), sitting diastolic blood pressure (DBP).
- Secondary Outcome Measures
Name Time Method Number of Participants Who Were Relapse Free From first dose to last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months) The number of participants who did not experience relapse. A relapse is defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by a relatively stable or improving neurological state of at least 30 days.
Average Number of New or Enlarging Hyperintense T2-Weighted Brain MRI Lesions Per Scan at Each Visit At 12 months post first dose and every 12 months thereafter up until 72 months post first dose. Adjusted Mean of new enlarging T2 lesions per scan at each visit. Based on a negative binomial regression model, adjusted for parent study, region (Eastern Europe vs. Rest of the World), age at Baseline, and baseline number of GdE lesions.
T2 Magnetic Resonance Imaging (MRI) sequences are used to highlight areas of demyelination in brain neurons, which happens when the outer layer of the neurons is damaged due to multiple sclerosis (MS) activity. T2 sequences can be used to count the total number of MS lesions, which look like bright white spots on T2 sequences, and can be called "hyperintense".Change in Multiple Sclerosis Quality of Life 54 Score From Baseline at Each Applicable Visit At baseline and every 12 months thereafter up until 84 months post first dose. The Multiple Sclerosis Quality of Life 54 (MSQOL-54) questionnaire is a health-related quality of life (HRQOL) instrument specific for multiple sclerosis (MS). This 54-item instrument generates 12 subscales along with two summary scores (physical health and mental health - derived from a weighted combination of scale scores), and two additional single-item measures. The subscales are: physical function, role limitations-physical, role limitations-emotional, pain, emotional well-being, energy, health perceptions, social function, cognitive function, health distress, overall quality of life, and sexual function. The MSQOL-54 items are transformed to 0-100 scores, and final scores are obtained by averaging items within the scales. The overall quality of life is assessed in question 54, which is scored on a scale of 0-100. Higher scores indicate better health-related quality of life. Baseline refers to assessments made on or before the first day participants received study treatment.
Change From Baseline in Volume of Gadolinium Enhanced T1 Lesions At baseline and every 12 months thereafter up until 72 months post first dose. Change from baseline in volume of gadolinium enhanced T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or "black holes" on a type of MRI scan. The growth of T1 lesions may mean the participant's Multiple Sclerosis (MS) is progressing.
Baseline refers to assessments made on or before the first day participants received study treatment.Cumulative Number of New Unenhancing T1 Lesions At baseline and every 12 months thereafter up until 72 months post first dose. Number of new unenhancing T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or "black holes" on a type of MRI scan. The appearance of new T1 lesions may mean the participant's MS is progressing.
Derived as the cumulative number of new or enlarging T1 lesions relative to baseline at a participant level.
Baseline refers to assessments made on or before the first day participants received study treatment.Average Number of Gadolinium-Enhanced (GdE) Brain MRI Lesions Per Scan at Each Visit At baseline and every 12 months thereafter up until 72 months post first dose. Number of gadolinium-enhanced (GdE) (also called GdE enhanced T1) brain MRI lesions per scan at each visit.
Increased numbers of GdE lesions indicates an increase in the in the amount of active inflammation at the site and may be indicative of progressive disease.
Based on a negative binomial regression model, adjusted for parent study, region (Eastern Europe vs. Rest of the World), age at Baseline, and Baseline number of GdE lesions.
Baseline refers to assessments made on or before the first day participants received study treatment.Annualized Relapse Rate (ARR) From first dose up until last dose of study treatment or data-cutoff date, whichever occurred first (up to approximately 87 months) The Annualized Relapse Rate (ARR) is the average number of relapses per study arm in one year. A relapse is defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS) and immediately preceded by a relatively stable or improving neurological state of at least 30 days. The adjusted ARR was based on the negative binomial regression model with parent treatment group, adjusted for region (Eastern Europe vs Rest of World), age at parent baseline, and the parent baseline number of gadolinium-enhanced (GdE) lesions. The natural log transformation of time on treatment was used as an offset term to adjust for participants having different exposure times.
Time to First Relapse (TFR) Overall: From first dose to first relapse, last dose, or data-cutoff date, whichever occurred first (up to approx 87 months); Visits: 2 weeks post first dose, 3 months post first dose, and every 3 months thereafter up until 81 months post first dose. The time between first dose of study treatment and first relapse if experienced by a participant. A participant was censored if follow-up ended before a relapse occurred, whether due to the participant completing study, withdrawing from the study, or due to the cutoff of data collection for the analysis. The censor date was the date of the end of study or the date of the data cutoff for participant who were ongoing. Participants who withdrew from the study after the baseline visit were censored at the last known date while on study. Based on Kaplan-Meier product limit estimates.
Time to Onset of Disability Progression as Defined by a Sustained Worsening in Expanded Disability Status Scale (EDSS) At 3 and 6 months post first dose. Multiple sclerosis (MS) disability progression is defined as a sustained worsening in EDSS of 1.0 points or more from baseline, confirmed after a 3-month and 6-month period. The EDSS is a standardized method, widely accepted, numerical scale used to evaluate disability in people with multiple sclerosis (MS). The EDSS is evaluated according to signs and symptoms observed during a standard neurological examination. These clinical observations are classified in 7 FS scales, each of them grading signs and symptoms for different neurological functions: pyramidal, cerebellar, brainstem, sensory, bowel or bladder, visual, and cerebral.
Derived using Kaplan-Meier estimates.Number of Participants Free of Gadolinium-Enhanced (GdE) Brain Lesions at Each Visit At baseline and every 12 months thereafter up until 72 months post first dose. Number of participants without gadolinium enhanced (GdE) brain MRI lesions at each visit. Increased numbers of GdE lesions indicates an increase in the in the amount of active inflammation at the site and may be indicative of progressive disease.
Based on cumulative number of GdE lesions at a participant level.Number of Participants Free of New or Enlarging T2 Lesions at Each Visit At baseline and every 12 months thereafter up until 72 months post first dose. Number of participants without new or enlarging T2 brain MRI lesions at each visit. Some multiple Sclerosis (MS) lesions appear as bright spots in a T2-weighted MRI scan - these are called T2 lesions. The presence of new or larger T2 lesions may mean the participant is at higher risk of disability and may have a less favorable long-term outcome.
Based on cumulative number of new or enlarging T2 lesions at a participant level.
Baseline refers to assessments made on or before the first day participants received study treatment.Percent Change in Normalized Brain Volume (Atrophy) on Brain MRI Scans From Baseline at Each Visit At baseline and every 12 months thereafter up until approximately 87 months post first dose. Percent change in normalized brain volume (Atrophy) on brain MRI scans from baseline at each visit. Brain atrophy can be seen in the earliest stages of multiple sclerosis (MS) and is a reliable predictor of future physical and cognitive disability.
Baseline refers to assessments made on or before the first day participants received study treatment.Change in Multiple Sclerosis Functional Composite (MSFC) Score From Baseline at Each Applicable Visit At baseline and every 12 months thereafter up until 84 months post first dose. The Multiple Sclerosis Functional Composite (MSFC) is a 3-part tool to measure disability progression in those with multiple sclerosis (MS). It assesses leg, arm, hand, and cognitive function using 3 individual scales: - The Timed 25-Foot Walk: To measure leg function - The 9-Hole Peg Test: To measure arm and hand function - The Symbol Digit Modalities Test (SDMT): To measure cognitive processing speed, flexibility, and calculation ability. Scores from each of the three are converted into Z-scores and averaged to create an overall composite score. The Low-Contrast Letter Acuity Test (LCLA) is performed with the MSFC using a set of charts to assess low contrast visual acuity. Each chart corresponds to a different contrast level, and charts are scored based on the number of letters identified correctly. A Z-score of 0 represents the population mean. Standard deviations above the mean represent a better outcome. Baseline refers to assessments on or before receiving study treatment.
Change From Baseline in Volume of T2 Lesions At baseline and every 12 months thereafter up until 72 months post first dose. Some multiple Sclerosis (MS) lesions appear as bright spots in a T2-weighted MRI scan - these are called T2 lesions. Larger T2 lesions may mean the participant is at higher risk of disability and may have a less favorable long-term outcome.
Baseline refers to assessments made on or before the first day participants received study treatment.Change From Baseline in Volume of Unenhancing T1 Lesions At baseline and every 12 months thereafter up until 72 months post first dose. Change from baseline in volume of unenhancing T1 lesions. T1-lesions are permanently damaged areas of the brain that appear as dark spots or "black holes" on a type of MRI scan. The growth of T1 lesions may mean the participant's Multiple Sclerosis (MS) is progressing.
Baseline refers to assessments made on or before the first day participants received study treatment.
Trial Locations
- Locations (175)
Local Institution - 110
🇺🇸Berkeley, California, United States
Local Institution - 123
🇺🇸Port Charlotte, Florida, United States
Local Institution - 179
🇺🇸Round Rock, Texas, United States
Local Institution - 921
🇭🇷Zagreb, Croatia
Local Institution - 103
🇺🇸Fresno, California, United States
Local Institution - 114
🇺🇸Maitland, Florida, United States
Local Institution - 144
🇺🇸Knoxville, Tennessee, United States
Local Institution - 460
🇧🇬Sofia, Bulgaria
Local Institution - 256
🇧🇪Brugge, Belgium
Local Institution - 496
🇩🇪Potsdam, Germany
Local Institution - 488
🇩🇪Ulm, Germany
Local Institution - 118
🇺🇸Phoenix, Arizona, United States
Local Institution - 124
🇺🇸Sunrise, Florida, United States
Local Institution - 147
🇺🇸Tampa, Florida, United States
Local Institution - 923
🇭🇷Osijek, Croatia
Local Institution - 653
🇮🇹Cefalu, Italy
Local Institution - 255
🇧🇪Bruxelles, Belgium
Local Institution - 903
🇧🇾Minsk, Belarus
Local Institution - 922
🇭🇷Zagreb, Croatia
Local Institution - 511
🇳🇿Christchurch, New Zealand
Local Institution - 122
🇺🇸Long Beach, California, United States
Local Institution - 252
🇧🇪Montegnee, Belgium
Local Institution - 654
🇮🇹Catania, Italy
Local Institution - 423
🇵🇱Bydgoszcz, Poland
Local Institution - 407
🇵🇱Katowice, Poland
Local Institution - 487
🇩🇪Leipzig, Germany
Local Institution - 401
🇵🇱Bialystok, Poland
Local Institution - 417
🇵🇱Katowice, Poland
Local Institution - 406
🇵🇱Czeladz, Poland
Local Institution - 621
🇱🇹Klaipeda, Lithuania
Local Institution - 429
🇵🇱Lublin, Poland
Local Institution - 510
🇳🇿Hamilton, New Zealand
Local Institution - 434
🇵🇱Warszawa, Mazowieckie, Poland
Local Institution - 822
🇺🇦Kyiv, Ukraine
Local Institution - 606
🇷🇸Nis, Serbia
Local Institution - 767
🇪🇸Valencia, Spain
Local Institution - 832
🇺🇦Kharkiv, Ukraine
Local Institution - 811
🇺🇦Kherson, Ukraine
Local Institution - 815
🇺🇦Dnipropetrovsk, Ukraine
Local Institution - 801
🇺🇦Ivano Frankivsk, Ukraine
Local Institution - 814
🇺🇦Kharkiv, Ukraine
Local Institution - 827
🇺🇦Kharkiv, Ukraine
Local Institution - 817
🇺🇦Lutsk, Ukraine
Local Institution - 820
🇺🇦Uzhhorod, Ukraine
Local Institution - 965
🇬🇧East Sussex, United Kingdom
Local Institution - 812
🇺🇦Lviv, Ukraine
Local Institution - 821
🇺🇦Lviv, Ukraine
Local Institution - 804
🇺🇦Odesa, Ukraine
Local Institution - 806
🇺🇦Zaporizhzhya, Ukraine
Local Institution - 963
🇬🇧Inverness, United Kingdom
Local Institution - 810
🇺🇦Odesa, Ukraine
Local Institution - 831
🇺🇦Odesa, Ukraine
Local Institution - 826
🇺🇦Poltava, Ukraine
Local Institution - 828
🇺🇦Zaporizhzhia, Ukraine
Local Institution - 964
🇬🇧Sheffield, United Kingdom
Local Institution - 819
🇺🇦Zhytomyr, Ukraine
Local Institution - 825
🇺🇦Zaporizhia, Ukraine
Local Institution - 115
🇺🇸Phoenix, Arizona, United States
Local Institution - 120
🇺🇸San Francisco, California, United States
Local Institution - 170
🇺🇸Las Vegas, Nevada, United States
Local Institution - 435
🇵🇱Rzeszow, Poland
Local Institution - 905
🇧🇾Vitebsk, Belarus
Local Institution - 306
🇬🇪Tbilisi, Georgia
Local Institution - 354
🇭🇺Esztergom, Hungary
Local Institution - 933
🇲🇩Chisinau, Moldova, Republic of
Local Institution - 906
🇧🇾Vitebsk, Belarus
Local Institution - 455
🇧🇬Sofia, Bulgaria
Local Institution - 901
🇧🇾Minsk, Belarus
Local Institution - 913
🇧🇦Banja Luka, Bosnia and Herzegovina
Local Institution - 456
🇧🇬Sofia, Bulgaria
Local Institution - 472
🇪🇪Tartu, Estonia
Local Institution - 552
🇬🇷Athens, Greece
Local Institution - 562
🇱🇻Riga, Latvia
Local Institution - 404
🇵🇱Konstancin Jeziorna, Poland
Local Institution - 420
🇵🇱Lublin, Poland
Local Institution - 431
🇵🇱Mazowieckie, Poland
Local Institution - 425
🇵🇱Pomorskie, Poland
Local Institution - 773
🇵🇹Torres Vedras, Portugal
Local Institution - 907
🇧🇾Grodno, Belarus
Local Institution - 454
🇧🇬Sofia, Bulgaria
Local Institution - 473
🇪🇪Tallinn, Estonia
Local Institution - 471
🇪🇪Tallinn, Estonia
Local Institution - 304
🇬🇪Tbilisi, Georgia
Local Institution - 911
🇧🇦Sarajevo, Bosnia and Herzegovina
Local Institution - 453
🇧🇬Sofia, Bulgaria
Local Institution - 452
🇧🇬Sofia, Bulgaria
Local Institution - 303
🇬🇪Tbilisi, Georgia
Local Institution - 551
🇬🇷Athens, Greece
Local Institution - 931
🇲🇩Chisinau, Moldova, Republic of
Local Institution - 432
🇵🇱Jaroslaw, Poland
Local Institution - 427
🇵🇱Katowice, Poland
Local Institution - 414
🇵🇱Krakow, Poland
Local Institution - 421
🇵🇱Plewiska, Poland
Local Institution - 356
🇭🇺Budapest, Hungary
Local Institution - 418
🇵🇱Poznan, Poland
Local Institution - 419
🇵🇱Szczecin, Poland
Local Institution - 301
🇬🇪Tbilisi, Georgia
Local Institution - 302
🇬🇪Tbilisi, Georgia
Local Institution - 553
🇬🇷Athens, Greece
Local Institution - 561
🇱🇻Riga, Latvia
Local Institution - 411
🇵🇱Lódzkie, Poland
Local Institution - 433
🇵🇱Rybnik, Poland
Local Institution - 428
🇵🇱Warszawa, Poland
Local Institution - 422
🇵🇱Warszawa, Poland
Local Institution - 504
🇷🇴Bucharest, Romania
Local Institution - 520
🇷🇴Bucharest, Romania
Local Institution - 507
🇷🇴Constanta, Romania
Local Institution - 603
🇷🇸Belgrade, Serbia
Local Institution - 555
🇬🇷Thessaloniki, Greece
Local Institution - 351
🇭🇺Nyiregyhaza, Hungary
Local Institution - 352
🇭🇺Budapest, Hungary
Local Institution - 622
🇱🇹Kaunas, Kauno Apskritis, Lithuania
Local Institution - 424
🇵🇱Kielce, Poland
Local Institution - 412
🇵🇱Lublin, Poland
Local Institution - 415
🇵🇱Olsztyn, Poland
Local Institution - 408
🇵🇱Poznan, Poland
Local Institution - 772
🇵🇹Braga, Portugal
Local Institution - 509
🇷🇴Bucharest, Romania
Local Institution - 942
🇸🇰Lucenec, Slovakia
Local Institution - 402
🇵🇱Warminsko-mazurskie, Poland
Local Institution - 410
🇵🇱Warsaw, Poland
Local Institution - 403
🇵🇱Warszawa, Poland
Local Institution - 755
🇪🇸Sevillla, Spain
Local Institution - 112
🇺🇸Sacramento, California, United States
Local Institution - 137
🇺🇸Golden Valley, Minnesota, United States
Local Institution - 107
🇺🇸Westerville, Ohio, United States
Local Institution - 138
🇺🇸Lubbock, Texas, United States
Local Institution - 143
🇺🇸Raleigh, North Carolina, United States
Local Institution - 904
🇧🇾Gomel, Belarus
Local Institution - 902
🇧🇾Minsk, Belarus
Local Institution - 141
🇺🇸Kirkland, Washington, United States
Local Institution - 457
🇧🇬Sofia, Bulgaria
Local Institution - 924
🇭🇷Zagreb, Croatia
Local Institution - 358
🇭🇺Kistarcsa, Hungary
Local Institution - 655
🇮🇹Milan, Italy
Local Institution - 932
🇲🇩Chisinau, Moldova, Republic of
Local Institution - 659
🇮🇹Montichiari, Italy
Local Institution - 651
🇮🇹Roma, Italy
Local Institution - 405
🇵🇱Gdansk, Poland
Local Institution - 426
🇵🇱Katowice, Poland
Local Institution - 605
🇷🇸Kragujevac, Serbia
Local Institution - 503
🇷🇴Brasov, Romania
Local Institution - 413
🇵🇱Warszawa, Poland
Local Institution - 775
🇵🇹Coimbra, Portugal
Local Institution - 502
🇷🇴Campulung, Romania
Local Institution - 508
🇷🇴Cluj Napoca, Romania
Local Institution - 506
🇷🇴Timisoara, Romania
Local Institution - 945
🇸🇰Trnava, Slovakia
Local Institution - 501
🇷🇴Cluj-Napoca, Romania
Local Institution - 602
🇷🇸Belgrade, Serbia
Local Institution - 604
🇷🇸Belgrade, Serbia
Local Institution - 601
🇷🇸Belgrade, Serbia
Local Institution - 946
🇸🇰Bratislava, Slovakia
Local Institution - 953
🇿🇦Pretoria, South Africa
Local Institution - 758
🇪🇸Barcelona, Spain
Local Institution - 756
🇪🇸Barcelona, Spain
Local Institution - 761
🇪🇸Bilbao, Spain
Local Institution - 757
🇪🇸Madrid, Spain
Local Institution - 760
🇪🇸Girona, Spain
Local Institution - 764
🇪🇸Pamplona/ Navarra, Spain
Local Institution - 759
🇪🇸San Sebastian, Spain
Local Institution - 754
🇪🇸Majadahonda, Spain
Local Institution - 766
🇪🇸Sant Joan Despí, Spain
Local Institution - 830
🇺🇦Chernihiv, Ukraine
Local Institution - 752
🇪🇸Valencia, Spain
Local Institution - 780
🇸🇪Goteborg, Sweden
Local Institution - 823
🇺🇦Cherkasy, Ukraine
Local Institution - 829
🇺🇦Ivano-Frankivsk, Ukraine
Local Institution - 813
🇺🇦Chernivtsi, Ukraine
Local Institution - 803
🇺🇦Kyiv, Ukraine
Local Institution - 818
🇺🇦Kyiv, Ukraine
Local Institution - 809
🇺🇦Vinnytsia, Ukraine
Local Institution - 805
🇺🇦Chernihiv, Ukraine
Local Institution - 824
🇺🇦Kyiv, Ukraine
Local Institution - 802
🇺🇦Dnipropetrovsk, Ukraine