Clinical trial NCT04338022: Study of Evobrutinib in Participants With RMS (evolutionRMS 1)
Official title: A Phase III, Multicenter, Randomized, Parallel Group, Double Blind, Double Dummy, Active Controlled Study of Evobrutinib Compared With Teriflunomide, in Participants With Relapsing Multiple Sclerosis to Evaluate Efficacy and Safety (evolutionRMS 1)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsing Multiple Sclerosis
Keywords: Evobrutinib
Teriflunomide
Aubagio®
Relapsing Multiple Sclerosis
Lead sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
Collaborators: name: EMD Serono Research & Development Institute, Inc.
First posted: 2020-04-08
Enrollment: 1124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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 \<= 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)
timeFrame: From baseline to 172 weeks
measure: Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs
timeFrame: From OLE Baseline (DBTP Week 96) to OLE Week 52
Secondary outcomes:
measure: DBTP and DBE Period: Percentage of Participants Without 12-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)
timeFrame: Week 96 and Week 156 (combined DBTP and DBE period)
measure: DBTP and DBE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)
timeFrame: Week 96 and Week 156 (combined DBTP and DBE periods)
measure: DBTP and DBE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS)
timeFrame: Week 96 and Week 156 (combined DBTP and DBE periods)
measure: 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
timeFrame: Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)
measure: 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
timeFrame: Baseline, Week 48, Week 96, Week 120, Week 144 and Week 156 (combined DBTP and DBE periods)
measure: DBTP and DBE Period: Total Number of T1 Gadolinium-positive (Gd+) Lesions
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Period: New or Enlarging T2 Lesions Rate
timeFrame: From baseline to 176 weeks
measure: DBTP Period: Neurofilament Light Chain Concentration (NfL) at Week 12
timeFrame: Week 12
measure: DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Adverse Events of Special Interest (AESIs)
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Vital Signs: Diastolic Blood Pressure and Systolic Blood Pressure
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Vital Signs: Pulse Rate
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Vital Signs: Respiratory Rate
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Vital Signs: Weight
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Vital Signs: Temperature
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameter: Heart Rate
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Electrocardiograms (ECGs) Parameters: QT Interval - Fridericia's Correction Formula, PR Interval and QRS Duration
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hemoglobin and Erythrocytes Mean Corpuscular Hemoglobin (HGB) Concentration
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Platelets, Leukocytes, Neutrophils, Eosinophils, Basophils, Monocytes, Lymphocytes and Reticulocytes
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Hematocrit
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Bilirubin and Creatinine
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Aspartate Aminotransferase, Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Lipase, Gamma Glutamyl Transferase and Lactate Dehydrogenase
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Sodium, Potassium, Calcium, Magnesium, Glucose, Chloride, Urea Nitrogen, Phosphate, Bicarbonate and Corrected Calcium
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Biochemistry Parameters: Total Protein and Albumin
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Biochemistry Parameter: Glomerular Filtration Rate
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Potential of Hydrogen (pH) of Urine
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Change From Baseline in Urinalyses Parameter: Specific Gravity of Urine
timeFrame: From baseline to 176 weeks
measure: DBTP and DBE Periods: Absolute Concentrations of Immunoglobulin (Ig) Levels
timeFrame: At Week 176
measure: DBTP and DBE Periods: Change From Baseline in Immunoglobulin (Ig) Levels
timeFrame: Baseline to 176 weeks
measure: OLE Period: Annualized Relapse Rate (ARR)
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
measure: OLE Period: Percentage of Participants Without 24-Week Confirmed Disability Progression (CDP) as Measured by Expanded Disability Status Scale (EDSS)
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
measure: OLE Period: Percentage of Participants With 24-Week Confirmed Disability Improvement (CDI) as Measured by Expanded Disability Status Scale (EDSS)
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
measure: OLE Period: Symbol Digit Modalities Test (SDMT)
timeFrame: Assessed from OLE baseline to OLE Week 96; OLE Week 48 were reported for Participants 1 and 2 and OLE Week 12 were reported for Participant 3
measure: OLE Period: Change From Baseline in PROMISnq Physical Function (PF) Multiple Sclerosis (MS) 15a at Week 52
timeFrame: OLE Baseline (DBTP Week 96), OLE Week 52
measure: OLE Period: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue (MS) 8a Score at Week 52
timeFrame: OLE baseline (DBTP Week 96), OLE Week 52
measure: OLE Period: Number of Participants With Abnormalities in Laboratory Parameters
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
measure: OLE Period: Number of Participants With Abnormalities in Vital Signs
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
measure: OLE Period: Number of Participants With Abnormalities in Electrocardiograms (ECGs) Findings
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
measure: OLE Period: Number of New or Enlarging T2 Lesions
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
measure: OLE Period: Change From Baseline in T2 Lesion Volume
timeFrame: From OLE baseline (DBTP Week 96) to OLE Week 52
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Research Site 629
state: Alabama
city: Phoenix
country: United States
facility: Research Site 614
state: Arizona
city: Phoenix
country: United States
facility: Research Site 677
state: Arizona
city: Long Beach
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facility: Research Site 642
state: California
city: Pasadena
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facility: Research Site 644
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city: San Diego
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facility: Research Site 672
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city: Washington
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facility: Research Site 656
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city: Maitland
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facility: Research Site 625
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city: Miami
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country: United States
facility: Research Site 649
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city: Peoria
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facility: Research Site 675
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city: Rolling Meadows
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facility: Research Site 628
state: Illinois
city: Indianapolis
country: United States
facility: Research Site 624
state: Indiana
city: Kansas City
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facility: Research Site 632
state: Kansas
city: New Orleans
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facility: Research Site 653
state: Louisiana
city: Baltimore
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facility: Research Site 623
state: Maryland
city: Boston
country: United States
facility: Research Site 633
state: Massachusetts
city: Foxboro
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facility: Research Site 639
state: Massachusetts
city: Lawrence
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facility: Research Site 635
state: Massachusetts
city: Worcester
country: United States
facility: Research Site 636
state: Massachusetts
city: Detroit
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facility: Research Site 613
state: Michigan
city: Farmington Hills
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facility: Research Site 612
state: Michigan
city: Saint Louis
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facility: Research Site 638
state: Missouri
city: Saint Louis
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facility: Research Site 664
state: Missouri
city: Omaha
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facility: Research Site 668
state: Nebraska
city: Las Vegas
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facility: Research Site 626
state: Nevada
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state: New Jersey
city: Patchogue
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facility: Research Site 620
state: New York
city: Akron
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facility: Research Site 663
state: Ohio
city: Toledo
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facility: Research Site 630
state: Ohio
city: Oklahoma City
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facility: Research Site 611
state: Oklahoma
city: Oklahoma City
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facility: Research Site 641
state: Oklahoma
city: Springfield
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facility: Research Site 615
state: Oregon
city: Willow Grove
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facility: Research Site 647
state: Pennsylvania
city: Knoxville
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facility: Research Site 648
state: Tennessee
city: Nashville
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facility: Research Site 627
state: Tennessee
city: Nashville
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facility: Research Site 637
state: Tennessee
city: Dallas
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facility: Research Site 662
state: Texas
city: Houston
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facility: Research Site 631
state: Texas
city: Lubbock
country: United States
facility: Research Site 650
state: Texas
city: Round Rock
country: United States
facility: Research Site 619
state: Texas
city: Layton
country: United States
facility: Research Site 676
state: Utah
city: Alexandria
country: United States
facility: Research Site 673
state: Virginia
city: Virginia Beach
country: United States
facility: Research Site 654
state: Virginia
city: Milwaukee
country: United States
facility: Research Site 651
state: Wisconsin
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site 566
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site 567
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site 574
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Research Site 579
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Research Site 561
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Research Site 562
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Research Site 577
city: Cordoba
country: Argentina
facility: Research Site 564
city: Godoy Cruz
country: Argentina
facility: Research Site 568
city: Guaymallen
country: Argentina
facility: Research Site 576
city: Rosario
country: Argentina
facility: Research Site 565
city: Rosario
country: Argentina
facility: Research Site 569
city: Salta
country: Argentina
facility: Research Site 571
city: San Juan
country: Argentina
facility: Research Site 572
city: San Miguel de Tucuman
country: Argentina
facility: Research Site 563
city: Auchenflower
country: Australia
facility: Research Site 104
city: Concord
country: Australia
facility: Research Site 107
city: Hobart
country: Australia
facility: Research Site 109
city: Liverpool
country: Australia
facility: Research Site 101
city: New Lambton Heights
country: Australia
facility: Research Site 102
city: St Leonards
country: Australia
facility: Research Site 103
city: Innsbruck
country: Austria
facility: Research Site 151
city: Linz
country: Austria
facility: Research Site 156
city: Salzburg
country: Austria
facility: Research Site 154
city: Vienna
country: Austria
facility: Research Site 153
city: Bruxelles
country: Belgium
facility: Research Site 474
city: Bruxelles
country: Belgium
facility: Research Site 475
city: Kortrijk
country: Belgium
facility: Research Site 473
city: La Louvière
country: Belgium
facility: Research Site 471
city: Liège
country: Belgium
facility: Research Site 472
city: Overpelt
country: Belgium
facility: Research Site 478
city: Roeselare
country: Belgium
facility: Research Site 476
city: Bihac
country: Bosnia and Herzegovina
facility: Research Site 161
city: Mostar
country: Bosnia and Herzegovina
facility: Research Site 163
city: Sarajevo
country: Bosnia and Herzegovina
facility: Research Site 162
city: Pleven
country: Bulgaria
facility: Research Site 171
city: Pleven
country: Bulgaria
facility: Research Site 174
city: Plovdiv
country: Bulgaria
facility: Reasearch Site 175
city: Plovdiv
country: Bulgaria
facility: Research Site 177
city: Sofia
country: Bulgaria
facility: Research Site 172
city: Sofia
country: Bulgaria
facility: Research Site 173
city: Sofia
country: Bulgaria
facility: Research Site 176
city: Sofia
country: Bulgaria
facility: Research Site 178
city: Sofia
country: Bulgaria
facility: Research Site 179
city: Sofia
country: Bulgaria
facility: Research Site 180
city: Greenfield Park
country: Canada
facility: Research Site 126
city: Levis
country: Canada
facility: Research Site 125
city: Moncton
country: Canada
facility: Research Site 128
city: Montreal
country: Canada
facility: Research Site 129
city: Toronto
country: Canada
facility: Research Site 124
city: Barranquilla
country: Colombia
facility: Research Site 591
city: Barranquilla
country: Colombia
facility: Research Site 597
city: Medellin
country: Colombia
facility: Research Site 592
city: Medellin
country: Colombia
facility: Research Site 600
city: Osijek
country: Croatia
facility: Research Site 193
city: Rijeka
country: Croatia
facility: Research Site 197
city: Varazdin
country: Croatia
facility: Research Site 195
city: Zagreb
country: Croatia
facility: Research Site 192
city: Zagreb
country: Croatia
facility: Research Site 194
city: Brno
country: Czechia
facility: Research Site 212
city: Brno
country: Czechia
facility: Research Site 218
city: Hradec Kralove
country: Czechia
facility: Research Site 219
city: Hradec Kralove
country: Czechia
facility: Research Site 222
city: Jihlava
country: Czechia
facility: Research Site 211
city: Ostrava
country: Czechia
facility: Research Site 223
city: Pardubice
country: Czechia
facility: Research Site 215
city: Plzen-Bory
country: Czechia
facility: Research Site 216
city: Praha 10
country: Czechia
facility: Research Site 217
city: Praha 2
country: Czechia
facility: Research Site 220
city: Praha 4 - Krc
country: Czechia
facility: Research Site 213
city: Praha 5
country: Czechia
facility: Research Site 224
city: Tallinn
country: Estonia
facility: Research Site 231
city: Tartu
country: Estonia
facility: Research Site 232
city: Turku
country: Finland
facility: Research Site 491
city: Bron cedex
country: France
facility: Research Site 510
city: Caen cedex 9
country: France
facility: Research Site 509
city: Grenoble cedex 09
country: France
facility: Research Site 502
city: Lille cedex
country: France
facility: Research Site 504
city: Lille
country: France
facility: Research Site 508
city: Montpellier
country: France
facility: Reserach Site 505
city: Nantes cedex 1
country: France
facility: Research Site 511
city: Nice Cedex 1
country: France
facility: Research Site 506
city: Rennes cedex 09
country: France
facility: Research Site 507
city: Rouen Cedex
country: France
facility: Research Site 501
city: Toulouse cedex 9
country: France
facility: Research Site 503
city: Tbilisi
country: Georgia
facility: Research Site 241
city: Tbilisi
country: Georgia
facility: Research Site 242
city: Tbilisi
country: Georgia
facility: Research Site 243
city: Tbilisi
country: Georgia
facility: Research Site 244
city: Tbilisi
country: Georgia
facility: Research Site 245
city: Tbilisi
country: Georgia
facility: Research Site 246
city: Tbilisi
country: Georgia
facility: Research Site 247
city: Tbilisi
country: Georgia
facility: Research Site 248
city: Tbilisi
country: Georgia
facility: Research Site 249
city: Tbilisi
country: Georgia
facility: Research Site 250
city: Bamberg
country: Germany
facility: Research Site 265
city: Bayreuth
country: Germany
facility: Research Site 267
city: Berlin
country: Germany
facility: Research Site 271
city: Bochum
country: Germany
facility: Research Site 264
city: Bonn
country: Germany
facility: Research Site 274
city: Erbach
country: Germany
facility: Research Site 270
city: Essen
country: Germany
facility: Research Site 268
city: Frankfurt
country: Germany
facility: Research Site 263
city: Hannover
country: Germany
facility: Research Site 275
city: Mannheim
country: Germany
facility: Research Site 272
city: Muenchen
country: Germany
facility: Research Site 262
city: Muenster
country: Germany
facility: Research Site 266
city: Potsdam
country: Germany
facility: Research Site 261
city: Siegen
country: Germany
facility: Research Site 273
city: Ulm
country: Germany
facility: Research Site 269
city: Hong Kong
country: Hong Kong
facility: Research Site 700
city: Hongkong
country: Hong Kong
facility: Research Site 704
city: Shatin
country: Hong Kong
facility: Research Site 701
city: Budapest
country: Hungary
facility: Research Site 282
city: Budapest
country: Hungary
facility: Research Site 285
city: Budapest
country: Hungary
facility: Research Site 286
city: Budapest
country: Hungary
facility: Research Site 288
city: Budapest
country: Hungary
facility: Research Site 290
city: Kistarcsa
country: Hungary
facility: Research Site 281
city: Pecs
country: Hungary
facility: Research Site 284
city: Tatabanya
country: Hungary
facility: Research Site 289
city: Vac
country: Hungary
facility: Research Site 291
city: Hyderabad
country: India
facility: Research Site 457
city: Nashik
country: India
facility: Research Site 456
city: New Delhi
country: India
facility: Research Site 451
city: Ashkelon
country: Israel
facility: Research Site 303
city: Jerusalem
country: Israel
facility: Research Site 305
city: Petah Tikva
country: Israel
facility: Research Site 307
city: Ramat Gan
country: Israel
facility: Research Site 308
city: Rechovot
country: Israel
facility: Research Site 301
city: Safed
country: Israel
facility: Research Site 304
city: Bologna
country: Italy
facility: Research Site 319
city: Chieti
country: Italy
facility: Research Site 321
city: Genova
country: Italy
facility: Research Site 322
city: Messina
country: Italy
facility: Research Site 320
city: Milano
country: Italy
facility: Research Site 315
city: Montichiari
country: Italy
facility: Research Site 314
city: Napoli
country: Italy
facility: Research Site 316
city: Napoli
country: Italy
facility: Research Site 317
city: Reggio Calabria
country: Italy
facility: Research Site 311
city: Roma
country: Italy
facility: Research Site 318
city: Salerno
country: Italy
facility: Research Site 312
city: Verona
country: Italy
facility: Research Site 313
city: Goyang-si
country: Korea, Republic of
facility: Research Site 462
city: Seoul
country: Korea, Republic of
facility: Research Site 461
city: Seoul
country: Korea, Republic of
facility: Research Site 463
city: Seoul
country: Korea, Republic of
facility: Research Site 464
city: Seoul
country: Korea, Republic of
facility: Research Site 465
city: Seoul
country: Korea, Republic of
facility: Research Site 466
city: Seoul
country: Korea, Republic of
facility: Research Site 467
city: Aguascalientes
country: Mexico
facility: Research Site 133
city: Culiacan
country: Mexico
facility: Research Site 134
city: Hoorn
country: Netherlands
facility: Research Site 534
city: Nieuwegein
country: Netherlands
facility: Research Site 531
city: Rotterdam
country: Netherlands
facility: Research Site 535
city: Sittard-Geleen
country: Netherlands
facility: Research Site 532
city: Bydgoszcz
country: Poland
facility: Research Site 332
city: Gdansk
country: Poland
facility: Research Site 335
city: Katowice
country: Poland
facility: Research Site 336
city: Knurow
country: Poland
facility: Research Site 340
city: Lodz
country: Poland
facility: Research Site 339
city: Lublin
country: Poland
facility: Research Site 337
city: Oswiecim
country: Poland
facility: Research Site 331
city: Rzeszów
country: Poland
facility: Research Site 338
city: Warszawa
country: Poland
facility: Research Site 341
city: Warszawa
country: Poland
facility: Research Site 342
city: Barnaul
country: Russian Federation
facility: Research Site 365
city: Ekaterinburg
country: Russian Federation
facility: Research Site 368
city: Kaluga
country: Russian Federation
facility: Research Site 355
city: Kazan
country: Russian Federation
facility: Research Site 358
city: Kirov
country: Russian Federation
facility: Research Site 354
city: Krasnoyarsk
country: Russian Federation
facility: Research Site 363
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
facility: Research Site 359
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site 352
city: Perm
country: Russian Federation
facility: Research Site 367
city: Pyatigorsk
country: Russian Federation
facility: Research Site 362
city: Saint-Petersburg
country: Russian Federation
facility: Research Site 369
city: Saratov
country: Russian Federation
facility: Research Site 360
city: Smolensk
country: Russian Federation
facility: Research Site 361
city: St.Petersburg
country: Russian Federation
facility: Research Site 356
city: Tomsk
country: Russian Federation
facility: Research Site 370
city: Ufa
country: Russian Federation
facility: Research Site 351
city: Ulyanovsk
country: Russian Federation
facility: Research Site 357
city: Yaroslavl
country: Russian Federation
facility: Research Site 366
city: Belgrade
country: Serbia
facility: Research Site 382
city: Belgrade
country: Serbia
facility: Research Site 383
city: Belgrade
country: Serbia
facility: Research Site 385
city: Kragujevac
country: Serbia
facility: Research Site 389
city: Nis
country: Serbia
facility: Research Site 390
city: Novi Sad
country: Serbia
facility: Research Site 388
city: Uzice
country: Serbia
facility: Research Site 384
city: Valjevo
country: Serbia
facility: Research Site 381
city: Barcelona
country: Spain
facility: Research Site 406
city: Barcelona
country: Spain
facility: Research Site 407
city: Cadiz
country: Spain
facility: Research Site 405
city: Lleida
country: Spain
facility: Research Site 401
city: Madrid
country: Spain
facility: Research Site 403
city: Madrid
country: Spain
facility: Research Site 408
city: Madrid
country: Spain
facility: Research Site 409
city: Pozuelo de Alarcon
country: Spain
facility: Research Site 411
city: Salt
country: Spain
facility: Research Site 410
city: San Sebastian
country: Spain
facility: Research Site 402
city: Sevilla
country: Spain
facility: Research Site 404
city: Kaohsiung
country: Taiwan
facility: Research site 713
city: Taichung
country: Taiwan
facility: Research Site 711
city: Taipei
country: Taiwan
facility: Research site 714
city: Taipei
country: Taiwan
facility: Research site 715
city: Chernivtsi
country: Ukraine
facility: Research Site 432
city: Kharkiv
country: Ukraine
facility: Research Site 425
city: Kharkiv
country: Ukraine
facility: Research Site 429
city: Kharkiv
country: Ukraine
facility: Research Site 430
city: Kharkiv
country: Ukraine
facility: Research Site 435
city: Kharkiv
country: Ukraine
facility: Research Site 436
city: Kharkiv
country: Ukraine
facility: Research Site 437
city: Kropyvnytskyi
country: Ukraine
facility: Research Site 422
city: Kyiv
country: Ukraine
facility: Research Site 438
city: Lviv
country: Ukraine
facility: Research Site 426
city: Odesa
country: Ukraine
facility: Research Site 424
city: Poltava
country: Ukraine
facility: Research Site 423
city: Sumy
country: Ukraine
facility: Research Site 427
city: Vinnytsia
country: Ukraine
facility: Research Site 431
city: Zaporizhzhia
country: Ukraine
facility: Research Site 421
city: Zaporizhzhia
country: Ukraine
facility: Research Site 428
city: Exeter
country: United Kingdom
facility: Research Site 544
city: Glasgow
country: United Kingdom
facility: Research Site 549
city: Newcastle
country: United Kingdom
facility: Research Site 552
city: Swansea
country: United Kingdom
facility: Research Site 547
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: Montalban X, Vermersch P, Arnold DL, Bar-Or A, Cree BAC, Cross AH, Kubala Havrdova E, Kappos L, Stuve O, Wiendl H, Wolinsky JS, Dahlke F, Le Bolay C, Shen Loo L, Gopalakrishnan S, Hyvert Y, Javor A, Guehring H, Tenenbaum N, Tomic D; evolutionRMS investigators. Safety and efficacy of evobrutinib in relapsing multiple sclerosis (evolutionRMS1 and evolutionRMS2): two multicentre, randomised, double-blind, active-controlled, phase 3 trials. Lancet Neurol. 2024 Nov;23(11):1119-1132. doi: 10.1016/S1474-4422(24)00328-4. Epub 2024 Sep 19.