Study of Evobrutinib in Participants With RMS (evolutionRMS 2)
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- Registration Number
- NCT04338061
- Lead Sponsor
- Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
- Brief Summary
The study is to evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Teriflunomide (Aubagio®), administered orally once daily in participants with Relapsing Multiple Sclerosis (RMS). Participants who complete the double-blind treatment period (DBTP) and double-blind extension period (DBEP) prior to approval of a separate long-term follow-up study in their country will get an option for evobrutinib treatment continuation through a 96-week open-label extension (OLE) period.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 1166
- Participants are diagnosed with RMS (relapsing-remitting multiple sclerosis [RRMS] or secondary progressive multiple sclerosis [SPMS] with relapses) in accordance with 2017 Revised McDonald criteria (Thompson 2018)
- Participants with one or more documented relapses within the 2 years before Screening with either: a. one relapse which occurred within the last year prior to randomization, OR b. the presence of at least 1 gadolinium-enhancing (Gd+) T1 lesion within 6 months prior to randomization
- Participants have Expanded Disability Status Scale (EDSS) score of 0 to 5.5 at Screening and Baseline (Day 1). Participants with an EDSS score less than or equal to [<=] 2 at Screening and Baseline (Day 1) are only eligible for participation if their disease duration (time since onset of symptoms) is no more than 10 years
- Participants are neurologically stable for >= 30 days prior to both screening and baseline (Day 1)
- Female participants must be neither pregnant nor breast-feeding or must lack child-bearing potential (as defined by either: post-menopausal or surgically sterile), or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure
- Male participants must refrain from donating sperm and/or abstain from intercourse with women of child-bearing potential or use an effective method of contraception for the duration of the study and at least 2 years after study intervention due to the long elimination period for teriflunomide of 2 years, unless the participant undergoes an accelerated elimination procedure
- Participants have given written informed consent prior to any study-related procedure
- Other protocol defined inclusion criteria could apply.
- Participants diagnosed with Progressive MS, in accordance with the 2017 Revised McDonald criteria as follows: a). Participants with Primary Progressive MS. b) Participants with secondary progressive MS without evidence of relapse
- Disease duration more than (>) 10 years in participants with an EDSS =< 2.0 at screening and Baseline (Day 1)
- Immunologic disorder other than MS, or any other condition requiring oral, intravenous (IV), intramuscular, or intra-articular corticosteroid therapy, with the exception of well-controlled Type 2 diabetes mellitus or well controlled thyroid disease
- Other protocol defined exclusion criteria could apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Teriflunomide Teriflunomide - Evobrutinib Evobrutinib -
- Primary Outcome Measures
Name Time Method Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR) Baseline up to 170 weeks The qualifying relapse is the occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than \[\>\] 24 hours, no fever, infection, injury, adverse events (AEs), and preceded by a stable or improving neurological state for more than or equal to \[\>=\] 30 days).
- Secondary Outcome Measures
Name Time Method DBTP and DBE Period: New or Enlarging T2 Lesions Rate Baseline up to 170 weeks Analysis of new or enlarging T2 lesions rate was done using magnetic resonance imaging (MRI) scans. Negative binomial model for lesion count (summed over scans) includes treatment and covariates based on randomization strata and baseline volume of T2 lesion (continuous), with offset equal to the log of the time in years between the last available MRI scan and the baseline scan.
DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) Week 96 and Week 156 (combined DBTP and DBE periods) Disability progression was defined as increase in EDSS of greater than or equal to \[\>=\] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of \>=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 12 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 12-week CDP.
DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS) Week 96 and Week 156 (combined DBTP and DBE periods) Disability progression was defined as increase in EDSS of greater than or equal to \[\>=\] 1 point from baseline EDSS score, if EDSS score at baseline is 5.0 or less and an increase of \>=0.5 point, if the baseline score is 5.5. Disability progression is considered sustained for 24 weeks when the initial increase in the EDSS is confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants without 24-week CDP.
DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS) Week 96 and Week 156 (combined DBTP and DBE periods) Disability improvement was defined as a reduction of 1 point from Baseline EDSS score when the Baseline score is \>= 2 and less than or equal to \[\<=\] 6 and a reduction of 0.5 point from Baseline EDSS score when the Baseline score is \>= 6.5 and \<= 9.5. Disability improvement is considered sustained when the initial reduction in the EDSS score is confirmed at a regularly scheduled visit at least 24 weeks after the initial reduction. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). Kaplan-Meier method was used to estimate the percentage of participants with 12-week CDI.
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (Combined DBTP and DBE periods) Physical function was assessed with PROMISnq Short Form v2.0 - Physical Function - Multiple Sclerosis 15a (PROMISnq PF(MS) 15a). PROMISnq PF(MS) 15a assesses a participant's abilities and limitations with respect to everyday physical activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 10 to 65. Higher T-scores represent higher physical function. Change from baseline in PROMIS PF score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).
DBTP and DBE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Score at Week 48, Week 96, Week 120, Week 144 and Week 156 Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 ((combined DBTP and DBE periods) PROMIS Fatigue score was assessed with PROMIS Short Form v1.0 - Fatigue - Multiple Sclerosis 8a (PROMIS Fatigue (MS) 8a). PROMIS Fatigue (MS) 8a assesses level of fatigue and its interference on daily activities. Results are reported as a T-score. In the general population, T-scores have a mean of 50, standard deviation of 10, and range from 33 to 85. Higher T-scores represent higher fatigue. Change from baseline in PROMIS fatigue score was analyzed using Mixed Effect Model for Repeated Measures (MMRM) to evaluate the result of the 2 periods (DBTP and DBE).
DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions Baseline up to 170 weeks Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans.
DBTP Period: Neurofilament Light Chain (NfL) Concentration at Week 12 Week 12 NfL is a biomarker of neuro-axonal damage whose concentration was assessed in blood at Week 12.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Bilirubin and Creatinine. Changes in biochemistry parameters: Bilirubin and Creatinine from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs) Baseline up to 170 weeks Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: those AEs with an onset date on or after the date of first study intervention administration, or AEs present prior to any study intervention administration but exacerbating after. TEAEs included both Serious TEAEs and non-serious TEAEs. AESIs included liver AEs (possible drug-induced, non-infectious, non-alcoholic, and immune-mediated), infections (serious and opportunistic infections), lipase and amylase elevation, and seizure.
DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity Baseline up to 170 weeks Severity of adverse events (AE) were assessed by the investigator per the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0. Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with Grades 1, 2, 3, 4 and 5 were reported.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure Baseline up to 170 weeks Diastolic blood pressure and systolic blood pressure were measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: diastolic blood pressure and systolic blood pressure from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate Baseline up to 170 weeks Pulse rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: pulse rate from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate Baseline up to 170 weeks Respiratory rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: respiratory rate from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight Baseline up to 170 weeks Changes in vital signs: weight from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature Baseline up to 170 weeks Temperature was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: Temperature from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): Heart Rate Baseline up to 170 weeks Heart rate was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: heart rate from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs): QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration Baseline up to 170 weeks QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration was measured after at least 5 minutes of rest for the participant in a quiet sitting without distractions. Changes in vital signs: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: erythrocytes mean corpuscular HGB concentration and hemoglobin. Changes in hematology parameters: erythrocytes mean corpuscular HGB concentration and hemoglobin from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes. Changes in hematology parameters: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Change From Baseline in Hematology Parameters: Hematocrit Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Hematocrit. Changes in hematology parameter: Hematocrit from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin. Changes in hematology parameter: Erythrocytes Mean Corpuscular Hemoglobin from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the hematology parameter: Erythrocytes Mean Corpuscular Volume. Changes in hematology parameter: Erythrocytes Mean Corpuscular Volume from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase. Changes in biochemistry parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium. Changes in biochemistry parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameters: Total Protein and Albumin. Changes in biochemistry parameters: Total Protein and Albumin from baseline up to 170 weeks were reported.
DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Glomerular Filtration Rate Baseline up to 170 weeks Blood samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the biochemistry parameter: Glomerular Filtration Rate. Changes in biochemistry parameter: Glomerular Filtration Rate from baseline up to 170 weeks were reported. The Glomerular Filtration Rate was measured as milliliter per minute per 1.73 square meter (mL/min/1.73m\^2).
DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine Baseline up to 170 weeks Urine samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the urinalyses parameter: pH. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Changes in urinalyses parameter: pH from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine Baseline up to 170 weeks Urine samples were collected in a fasted condition (after a fast of at least 12 hours) to analyze the urinalyses parameter: Specific Gravity of Urine. Changes in urinalyses parameter: Specific Gravity of Urine from baseline up to 170 weeks was reported.
DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels At Week 170 Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels Baseline up to 170 weeks Change from baseline serum levels of IgG, IgA, IgM were assessed.
Trial Locations
- Locations (278)
Research Site 730
🇺🇸Raleigh, North Carolina, United States
Research Site 269
🇵🇱Wroclaw, Poland
Research Site 752
🇺🇸Cullman, Alabama, United States
Research Site 741
🇺🇸Scottsdale, Arizona, United States
Research Site 704
🇺🇸Tucson, Arizona, United States
Research Site 751
🇺🇸Hanford, California, United States
Research Site 737
🇺🇸West Hollywood, California, United States
Research Site 759
🇺🇸Colorado Springs, Colorado, United States
Research Site 725
🇺🇸Fort Collins, Colorado, United States
Research Site 746
🇺🇸Altamonte Springs, Florida, United States
Research Site 718
🇺🇸Jacksonville, Florida, United States
Research Site 702
🇺🇸Naples, Florida, United States
Research Site 740
🇺🇸Orlando, Florida, United States
Research Site 726
🇺🇸Port Charlotte, Florida, United States
Research Site 719
🇺🇸Sarasota, Florida, United States
Research Site 707
🇺🇸Tampa, Florida, United States
Research Site 738
🇺🇸Detroit, Michigan, United States
Research Site 736
🇺🇸Asheville, North Carolina, United States
Research Site 712
🇺🇸Chapel Hill, North Carolina, United States
Research Site 728
🇺🇸Winston-Salem, North Carolina, United States
Research Site 711
🇺🇸Canton, Ohio, United States
Research Site 743
🇺🇸Tampa, Florida, United States
Research Site 732
🇺🇸Vero Beach, Florida, United States
Research Site 705
🇺🇸Weeki Wachee, Florida, United States
Research Site 714
🇺🇸Fort Wayne, Indiana, United States
Research Site 744
🇺🇸Lafayette, Indiana, United States
Research Site 717
🇺🇸Overland Park, Kansas, United States
Research Site 735
🇺🇸Nicholasville, Kentucky, United States
Research Site 706
🇺🇸Scarborough, Maine, United States
Research Site 723
🇺🇸Saint Louis, Missouri, United States
Research Site 724
🇺🇸Amherst, New York, United States
Research Site 757
🇺🇸Columbus, Ohio, United States
Research Site 734
🇺🇸Dayton, Ohio, United States
Research Site 748
🇺🇸Philadelphia, Pennsylvania, United States
Research Site 703
🇺🇸San Antonio, Texas, United States
Research Site 753
🇺🇸West Palm Beach, Florida, United States
Research Site 742
🇺🇸Honolulu, Hawaii, United States
Research Site 715
🇺🇸Evanston, Illinois, United States
Research Site 144
🇧🇾Gomel, Belarus
Research Site 143
🇧🇾Grodno, Belarus
Research Site 721
🇺🇸Norfolk, Virginia, United States
Research Site 142
🇧🇾Minsk, Belarus
Research Site 141
🇧🇾Vitebsk, Belarus
Research Site 145
🇧🇾Vitebsk, Belarus
Research Site 603
🇧🇷Belo Horizonte, Brazil
Research Site 599
🇧🇷Curitiba, Brazil
Research Site 604
🇧🇷Goiânia, Brazil
Research Site 600
🇧🇷Joinville, Brazil
Research Site 614
🇧🇷Passo Fundo, Brazil
Research Site 591
🇧🇷Porto Alegre, Brazil
Research Site 594
🇧🇷Porto Alegre, Brazil
Research Site 596
🇧🇷Porto Alegre, Brazil
Research Site 609
🇧🇷Vitória, Brazil
Research Site 155
🇧🇬Blagoevgrad, Bulgaria
Research Site 156
🇧🇬Dupnitsa, Bulgaria
Research Site 157
🇧🇬Pleven, Bulgaria
Research Site 801
🇧🇬Pleven, Bulgaria
Research Site 804
🇧🇬Pleven, Bulgaria
Research Site 805
🇧🇬Plovdiv, Bulgaria
Research Site 151
🇧🇬Sofia, Bulgaria
Research Site 152
🇧🇬Sofia, Bulgaria
Research Site 153
🇧🇬Sofia, Bulgaria
Research Site 158
🇧🇬Sofia, Bulgaria
Research Site 159
🇧🇬Sofia, Bulgaria
Research Site 160
🇧🇬Sofia, Bulgaria
Research Site 802
🇧🇬Sofia, Bulgaria
Research Site 803
🇧🇬Sofia, Bulgaria
Research Site 808
🇧🇬Sofia, Bulgaria
Research Site 154
🇧🇬Veliko Tarnovo, Bulgaria
Research Site 106
🇨🇦Burnaby, Canada
Research Site 107
🇨🇦London, Canada
Research Site 105
🇨🇦Montreal, Canada
Research Site 101
🇨🇦Ottawa, Canada
Research Site 455
🇫🇷Bordeaux Cedex, France
Research Site 459
🇫🇷Brest cedex 2, France
Reserach Site 451
🇫🇷Clermont Ferrand Cedex, France
Research Site 458
🇫🇷Limoges cedex, France
Research Site 456
🇫🇷Nimes, France
Research Site 453
🇫🇷Paris, France
Research Site 457
🇫🇷Pringy cedex, France
Research Site 452
🇫🇷Strasbourg cedex, France
Research Site 454
🇫🇷Tours cedex 9, France
Research Site 172
🇩🇪Augsburg, Germany
Research Site 177
🇩🇪Berlin, Germany
Research Site 180
🇩🇪Berlin, Germany
Research Site 178
🇩🇪Bonn, Germany
Research Site 184
🇩🇪Dresden, Germany
Research Site 174
🇩🇪Hamburg, Germany
Research Site 182
🇩🇪Heidelberg, Germany
Research Site 202
🇬🇷Athens, Greece
Reserach Site 206
🇬🇷Athens, Greece
Research Site 204
🇬🇷Ioannina, Greece
Research Site 192
🇬🇷Larissa, Greece
Research Site 191
🇬🇷Patras, Greece
Research Site 445
🇮🇳Ahmedabad, India
Research Site 179
🇩🇪Koeln, Germany
Research Site 181
🇩🇪Leipzig, Germany
Research Site 173
🇩🇪Mainz, Germany
Research Site 183
🇩🇪Rostock, Germany
Research Site 175
🇩🇪Tuebingen, Germany
Research Site 196
🇬🇷Athens, Greece
Research Site 197
🇬🇷Athens, Greece
Research Site 201
🇬🇷Athens, Greece
Research Site 176
🇩🇪Minden, Germany
Research Site 171
🇩🇪Regensburg, Germany
Research Site 194
🇬🇷Athens, Greece
Research Site 205
🇬🇷Athens, Greece
Research Site 207
🇬🇷Athens, Greece
Research Site 198
🇬🇷Heraklion, Greece
Research Site 199
🇬🇷Marousi, Greece
Research Site 203
🇬🇷Patra, Greece
Research Site 195
🇬🇷Thessaloniki, Greece
Research Site 212
🇮🇹Pozzilli, Italy
Research Site 233
🇱🇻Riga, Latvia
Research site 241
🇱🇹Kaunas, Lithuania
Research site 244
🇱🇹Klaipeda, Lithuania
Research site 242
🇱🇹Vilnius, Lithuania
Research Site 252
🇲🇩Chisinau, Moldova, Republic of
Research Site 276
🇵🇱Krakow, Poland
Research Site 263
🇵🇱Lodz, Poland
Research Site 270
🇵🇱Poznan, Poland
Research Site 444
🇮🇳Bangalore, India
Research Site 443
🇮🇳Mangalore, India
Research Site 222
🇮🇹Roma, Italy
Research Site 231
🇱🇻Riga, Latvia
Research Site 232
🇱🇻Riga, Latvia
Research site 243
🇱🇹Siauliai, Lithuania
Research Site 442
🇮🇳New Delhi, India
Research Site 218
🇮🇹Bari, Italy
Research Site 216
🇮🇹Catania, Italy
Research Site 214
🇮🇹Cefalù, Italy
Research Site 219
🇮🇹Firenze, Italy
Research Site 221
🇮🇹Milano, Italy
Research Site 211
🇮🇹Napoli, Italy
Research Site 215
🇮🇹Napoli, Italy
Research Site 220
🇮🇹Orbassano, Italy
Research Site 217
🇮🇹Palermo, Italy
Research Site 213
🇮🇹Roma, Italy
Research Site 551
🇲🇾Kuala Lumpur, Malaysia
Research Site 554
🇲🇾Kuala Lumpur, Malaysia
Research Site 556
🇲🇾Kuala Lumpur, Malaysia
Research Site 552
🇲🇾Kuching, Malaysia
Research Site 553
🇲🇾Seberang Jaya, Malaysia
Research Site 251
🇲🇩Chisinau, Moldova, Republic of
Research Site 481
🇳🇴Bergen, Norway
Research site 483
🇳🇴Drammen, Norway
Research Site 482
🇳🇴Namsos, Norway
Research Site 562
🇵🇭Baguio City, Philippines
Research Site 561
🇵🇭Cebu City, Philippines
Reserach Site 267
🇵🇱Bydgoszcz, Poland
Reserach Site 268
🇵🇱Bydgoszcz, Poland
Research site 274
🇵🇱Katowice-Ochojec, Poland
Research Site 273
🇵🇱Katowice, Poland
Research site 846
🇵🇱Katowice, Poland
Research Site 261
🇵🇱Zabrze, Poland
Research Site 278
🇵🇱Zamosc, Poland
Research Site 272
🇵🇱Łódź, Poland
Research Site 293
🇵🇹Aveiro, Portugal
Research Site 282
🇵🇹Braga, Portugal
Research Site 289
🇵🇹Coimbra, Portugal
Research Site 281
🇵🇹Lisboa, Portugal
Research Site 266
🇵🇱Nowa Sol, Poland
Research Site 262
🇵🇱Rzeszow, Poland
Research Site 271
🇵🇱Szczecin, Poland
Research Site 329
🇷🇺Kazan, Russian Federation
Research Site 323
🇷🇺Kemerovo, Russian Federation
Research Site 330
🇷🇺Novosibirsk, Russian Federation
Research Site 331
🇷🇺Novosibirsk, Russian Federation
Research Site 324
🇷🇺Saint-Petersburg, Russian Federation
Research Site 265
🇵🇱Siemianowice, Poland
Research Site 264
🇵🇱Warszawa, Poland
Research Site 277
🇵🇱Warszawa, Poland
Reserach Site 275
🇵🇱Warszawa, Poland
Research Site 283
🇵🇹Lisboa, Portugal
Research Site 287
🇵🇹Lisboa, Portugal
Research SIte 284
🇵🇹Matosinhos, Portugal
Research Site 292
🇵🇹Porto, Portugal
Research Site 288
🇵🇹Pragal, Portugal
Research Site 291
🇵🇹Santa Maria da Feira, Portugal
Research Site 286
🇵🇹Torres Vedras, Portugal
Research Site 791
🇵🇷Guaynabo, Puerto Rico
Research Site 314
🇷🇴Brasov, Romania
Research Site 307
🇷🇴București, Romania
Research Site 309
🇷🇴Caracal, Romania
Research Site 302
🇷🇴Targu Mures, Romania
Research Site 344
🇷🇺Kirov, Russian Federation
Research Site 340
🇷🇺Krasnodar, Russian Federation
Research Site 325
🇷🇺Kazan, Russian Federation
Research Site 334
🇷🇺Krasnoyarsk, Russian Federation
Research Site 341
🇷🇺Moscow, Russian Federation
Research Site 343
🇷🇺Moscow, Russian Federation
Research Site 345
🇷🇺Moscow, Russian Federation
Research Site 332
🇷🇺Nizhniy Novgorod, Russian Federation
Research Site 327
🇷🇺Novosibirsk, Russian Federation
Research Site 335
🇷🇺Novosibirsk, Russian Federation
Research Site 338
🇷🇺Saint-Petersburg, Russian Federation
Research Site 339
🇷🇺Saint-Petersburg, Russian Federation
Research Site 342
🇷🇺Saint-Petersburg, Russian Federation
Research Site 326
🇷🇺Saransk, Russian Federation
Research Site 321
🇷🇺Sestroretsk, Russian Federation
Research Site 337
🇷🇺Tyumen, Russian Federation
Research Site 328
🇷🇺Rostov-on-Don, Russian Federation
Research Site 346
🇷🇺Saint Petersburg, Russian Federation
Research Site 493
🇸🇦Riyadh, Saudi Arabia
Research Site 571
🇸🇬Singapore, Singapore
Research site 572
🇸🇬Singapore, Singapore
Research Site 351
🇸🇰Banska Bystrica, Slovakia
Research Site 352
🇸🇰Bratislava, Slovakia
Research Site 353
🇸🇰Bratislava, Slovakia
Research Site 354
🇸🇰Bratislava, Slovakia
Research Site 356
🇸🇰Bratislava, Slovakia
Research Site 359
🇸🇰Dubnica nad Vahom, Slovakia
Research Site 358
🇸🇰Trencin, Slovakia
Research Site 357
🇸🇰Trnava, Slovakia
Research Site 373
🇸🇮Celje, Slovenia
Research Site 372
🇸🇮Ljubljana, Slovenia
Research Site 371
🇸🇮Maribor, Slovenia
Research Site 501
🇿🇦Cape Town, South Africa
Research Site 502
🇿🇦Cape Town, South Africa
Research Site 503
🇿🇦Cape Town, South Africa
Research Site 504
🇿🇦Pretoria, South Africa
Research Site 384
🇪🇸Alcorcon, Spain
Research Site 391
🇪🇸Barakaldo, Spain
Research Site 390
🇪🇸Barcelona, Spain
Research Site 382
🇪🇸Cordoba, Spain
Research Site 389
🇪🇸El Palmar, Spain
Research Site 388
🇪🇸Madrid, Spain
Research Site 392
🇪🇸Majadahonda, Spain
Research Site 383
🇪🇸Malaga, Spain
Research Site 387
🇪🇸Sevilla, Spain
Research Site 385
🇪🇸Valencia, Spain
Research Site 386
🇪🇸Valencia, Spain
Research Site 381
🇪🇸Vigo, Spain
Research Site 512
🇸🇪Göteborg, Sweden
Research site 514
🇸🇪Malmö, Sweden
Research Site 511
🇸🇪Stockholm, Sweden
Research Site 513
🇸🇪Uppsala, Sweden
Research Site 404
🇨🇭Aarau, Switzerland
Research Site 402
🇨🇭Bern, Switzerland
Research Site 583
🇹🇭Bangkoknoi, Thailand
Research Site 403
🇨🇭Lugano, Switzerland
Research Site 582
🇹🇭Muang, Thailand
Research Site 538
🇹🇷Ankara, Turkey
Research Site 544
🇹🇷Ankara, Turkey
Research Site 531
🇹🇷Istanbul, Turkey
Research Site 534
🇹🇷Istanbul, Turkey
Research Site 536
🇹🇷Istanbul, Turkey
Research Site 541
🇹🇷Istanbul, Turkey
Research Site 543
🇹🇷Istanbul, Turkey
Research Site 539
🇹🇷Izmir, Turkey
Research Site 533
🇹🇷Kocaeli, Turkey
Research Site 537
🇹🇷Konya, Turkey
Research Site 540
🇹🇷Mersin, Turkey
Research Site 535
🇹🇷Samsun, Turkey
Research Site 532
🇹🇷Trabzon, Turkey
Research Site 415
🇺🇦Chernihiv, Ukraine
Research Site 417
🇺🇦Chernihiv, Ukraine
Research Site 414
🇺🇦Dnipro, Ukraine
Research Site 416
🇺🇦Dnipro, Ukraine
Research Site 420
🇺🇦Dnipro, Ukraine
Research Site 413
🇺🇦Ivano-Frankivsk, Ukraine
Research Site 624
🇺🇦Kharkiv, Ukraine
Research Site 632
🇺🇦Kharkiv, Ukraine
Research Site 633
🇺🇦Kharkiv, Ukraine
Research Site 419
🇺🇦Kherson, Ukraine
Research Site 411
🇺🇦Kyiv, Ukraine
Research Site 418
🇺🇦Kyiv, Ukraine
Research Site 629
🇺🇦Lutsk, Ukraine
Research Site 627
🇺🇦Lviv, Ukraine
Research Site 622
🇺🇦Poltava, Ukraine
Research Site 625
🇺🇦Rivne, Ukraine
Research Site 628
🇺🇦Ternopil, Ukraine
Research Site 630
🇺🇦Uzhgorod, Ukraine
Research Site 623
🇺🇦Vinnytsia, Ukraine
Research Site 412
🇺🇦Zaporizhzhia, Ukraine
Research Site 621
🇺🇦Zaporizhzhia, Ukraine
Research Site 631
🇺🇦Zaporizhzhia, Ukraine
Research Site 626
🇺🇦Zhytomyr, Ukraine