Study Stopped
Primary analysis of the RMS phase 3 study (MS200527\_0080) resulted in the early termination of the study.
Study of Evobrutinib in Participants With RMS (evolutionRMS 1)
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)
2 other identifiers
interventional
1,124
29 countries
264
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jun 2020
Typical duration for phase_3
264 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 6, 2020
CompletedFirst Posted
Study publicly available on registry
April 8, 2020
CompletedStudy Start
First participant enrolled
June 12, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 2, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
March 8, 2024
CompletedResults Posted
Study results publicly available
June 12, 2025
CompletedJune 12, 2025
May 1, 2025
3.3 years
April 6, 2020
October 1, 2024
May 26, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Double Blind Treatment Period (DBTP) and Double Blind Extension (DBE) Period: Annualized Relapse Rate (ARR)
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).
From baseline to 172 weeks
Open Label Extension (OLE) Period: Number of Participants With Adverse Events (AEs) and Serious AEs
Adverse event (AE): Any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to 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.
From OLE Baseline (DBTP Week 96) to OLE Week 52
Secondary Outcomes (42)
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 period)
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)
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)
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)
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)
- +37 more secondary outcomes
Study Arms (2)
Teriflunomide
ACTIVE COMPARATOREvobrutinib
EXPERIMENTALInterventions
Participants received Teriflunomide at a dose of 14 milligrams (mg) orally once daily up to 156 weeks in Double blind treatment period (DBTP) followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in double blind extension (DBE) period and followed by once daily oral doses of Teriflunomide 14 mg up to 96 weeks in open label extension (OLE) period.
Participants received Evobrutinib at a dose of 45 mg orally twice daily up to 156 weeks in Double blind treatment period (DBTP) followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in double blind extension (DBE) period and followed by twice daily oral doses of Evobrutinib 45 mg up to 96 weeks in open label extension (OLE) period.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (279)
Research Site 629
Mobile, Alabama, 36693-7003, United States
Research Site 614
Phoenix, Arizona, 85013, United States
Research Site 677
Phoenix, Arizona, 85018, United States
Research Site 642
Long Beach, California, 90806, United States
Research Site 644
Pasadena, California, 91105, United States
Research Site 672
San Diego, California, 92121, United States
Research Site 634
Stamford, Connecticut, 06905, United States
Research Site 656
Washington D.C., District of Columbia, 20007, United States
Research Site 616
Boca Raton, Florida, 33428, United States
Research Site 625
Maitland, Florida, 32751, United States
Research Site 617
Miami, Florida, 33136, United States
Research Site 643
Ormond Beach, Florida, 32174, United States
Research site 645
St. Petersburg, Florida, 33713, United States
Research Site 652
Tallahassee, Florida, 32308, United States
Research Site 621
Elk Grove Village, Illinois, 60007, United States
Research Site 649
Northbrook, Illinois, 60062, United States
Research Site 675
Peoria, Illinois, 61637, United States
Research Site 628
Rolling Meadows, Illinois, 60008, United States
Research Site 624
Indianapolis, Indiana, 46256, United States
Research Site 632
Kansas City, Kansas, 66160, United States
Research Site 653
New Orleans, Louisiana, 70115, United States
Research Site 623
Baltimore, Maryland, 21201, United States
Research Site 633
Boston, Massachusetts, 02114, United States
Research Site 639
Foxborough, Massachusetts, 02035, United States
Research Site 635
Lawrence, Massachusetts, 01843, United States
Research Site 636
Worcester, Massachusetts, 01655, United States
Research Site 613
Detroit, Michigan, 48201, United States
Research Site 612
Farmington Hills, Michigan, 48334, United States
Research Site 638
St Louis, Missouri, 63110, United States
Research Site 664
St Louis, Missouri, 63131, United States
Research Site 668
Omaha, Nebraska, 68130, United States
Research Site 626
Las Vegas, Nevada, 89106, United States
Research Site 667
Audubon, New Jersey, 08106, United States
Research Site 620
Patchogue, New York, 11772, United States
Research Site 663
Akron, Ohio, 44320, United States
Research Site 630
Toledo, Ohio, 43614-2598, United States
Research Site 611
Oklahoma City, Oklahoma, 73104, United States
Research Site 641
Oklahoma City, Oklahoma, 73104, United States
Research Site 615
Springfield, Oregon, 97477, United States
Research Site 647
Willow Grove, Pennsylvania, 19090, United States
Research Site 648
Knoxville, Tennessee, 37922, United States
Research Site 627
Nashville, Tennessee, 37205, United States
Research Site 637
Nashville, Tennessee, 37215, United States
Research Site 662
Dallas, Texas, 75214, United States
Research Site 631
Houston, Texas, 77030, United States
Research Site 650
Lubbock, Texas, 79410, United States
Research Site 619
Round Rock, Texas, 78681, United States
Research Site 676
Layton, Utah, 84041, United States
Research Site 673
Alexandria, Virginia, 22310, United States
Research Site 654
Virginia Beach, Virginia, 23456, United States
Research Site 651
Milwaukee, Wisconsin, 53226-3596, United States
Research Site 561
Buenos Aires, Argentina
Research Site 562
Buenos Aires, Argentina
Research Site 577
Buenos Aires, Argentina
Research Site 566
Ciudad Autonoma Buenos Aires, Argentina
Research Site 567
Ciudad Autonoma Buenos Aires, Argentina
Research Site 574
Ciudad Autonoma Buenos Aires, Argentina
Research Site 579
Ciudad Autonoma Buenos Aires, Argentina
Research Site 564
Córdoba, Argentina
Research Site 568
Godoy Cruz, Argentina
Research Site 565
Rosario, Argentina
Research Site 569
Rosario, Argentina
Research Site 571
Salta, Argentina
Research Site 572
San Juan, Argentina
Research Site 563
San Miguel de Tucumán, Argentina
Research Site 576
Villa Nueva, Argentina
Research Site 104
Auchenflower, Australia
Research Site 107
Concord, Australia
Research Site 109
Hobart, Australia
Research Site 101
Liverpool, Australia
Research Site 102
New Lambton Heights, Australia
Research Site 103
St Leonards, Australia
Research Site 151
Innsbruck, Austria
Research Site 156
Linz, Austria
Research Site 154
Salzburg, Austria
Research Site 153
Vienna, Austria
Research Site 474
Brussels, Belgium
Research Site 475
Brussels, Belgium
Research Site 473
Kortrijk, Belgium
Research Site 471
La Louvière, Belgium
Research Site 472
Liège, Belgium
Research Site 478
Overpelt, Belgium
Research Site 476
Roeselare, Belgium
Research Site 161
Bihać, Bosnia and Herzegovina
Research Site 163
Mostar, Bosnia and Herzegovina
Research Site 162
Sarajevo, Bosnia and Herzegovina
Research Site 171
Pleven, Bulgaria
Research Site 174
Pleven, Bulgaria
Reasearch Site 175
Plovdiv, Bulgaria
Research Site 177
Plovdiv, Bulgaria
Research Site 172
Sofia, Bulgaria
Research Site 173
Sofia, Bulgaria
Research Site 176
Sofia, Bulgaria
Research Site 178
Sofia, Bulgaria
Research Site 179
Sofia, Bulgaria
Research Site 180
Sofia, Bulgaria
Research Site 126
Greenfield Park, Canada
Research Site 125
Lévis, Canada
Research Site 128
Moncton, Canada
Research Site 129
Montreal, Canada
Research Site 124
Toronto, Canada
Research Site 591
Barranquilla, Colombia
Research Site 597
Barranquilla, Colombia
Research Site 592
Medellín, Colombia
Research Site 600
Medellín, Colombia
Research Site 193
Osijek, Croatia
Research Site 197
Rijeka, Croatia
Research Site 195
Varaždin, Croatia
Research Site 192
Zagreb, Croatia
Research Site 194
Zagreb, Croatia
Research Site 212
Brno, Czechia
Research Site 218
Brno, Czechia
Research Site 219
Hradec Králové, Czechia
Research Site 222
Hradec Králové, Czechia
Research Site 211
Jihlava, Czechia
Research Site 223
Ostrava, Czechia
Research Site 215
Pardubice, Czechia
Research Site 216
Plzen-Bory, Czechia
Research Site 217
Prague, Czechia
Research Site 220
Prague, Czechia
Research Site 224
Prague, Czechia
Research Site 213
Praha 4 - Krc, Czechia
Research Site 231
Tallinn, Estonia
Research Site 232
Tartu, Estonia
Research Site 491
Turku, Finland
Research Site 510
Bron, France
Research Site 509
Caen, France
Research Site 502
Grenoble, France
Research Site 504
Lille, France
Research Site 508
Lille, France
Reserach Site 505
Montpellier, France
Research Site 511
Nantes, France
Research Site 506
Nice, France
Research Site 507
Rennes, France
Research Site 501
Rouen, France
Research Site 503
Toulouse, France
Research Site 241
Tbilisi, Georgia
Research Site 242
Tbilisi, Georgia
Research Site 243
Tbilisi, Georgia
Research Site 244
Tbilisi, Georgia
Research Site 245
Tbilisi, Georgia
Research Site 246
Tbilisi, Georgia
Research Site 247
Tbilisi, Georgia
Research Site 248
Tbilisi, Georgia
Research Site 249
Tbilisi, Georgia
Research Site 250
Tbilisi, Georgia
Research Site 265
Bamberg, Germany
Research Site 267
Bayreuth, Germany
Research Site 271
Berlin, Germany
Research Site 264
Bochum, Germany
Research Site 274
Bonn, Germany
Research Site 270
Erbach im Odenwald, Germany
Research Site 268
Essen, Germany
Research Site 263
Frankfurt, Germany
Research Site 275
Hanover, Germany
Research Site 272
Mannheim, Germany
Research Site 262
München, Germany
Research Site 266
Münster, Germany
Research Site 261
Potsdam, Germany
Research Site 273
Siegen, Germany
Research Site 269
Ulm, Germany
Research Site 700
Hong Kong, Hong Kong
Research Site 704
Hong Kong, Hong Kong
Research Site 701
Shatin, Hong Kong
Research Site 282
Budapest, Hungary
Research Site 285
Budapest, Hungary
Research Site 286
Budapest, Hungary
Research Site 288
Budapest, Hungary
Research Site 290
Budapest, Hungary
Research Site 281
Kistarcsa, Hungary
Research Site 284
Pécs, Hungary
Research Site 289
Tatabánya, Hungary
Research Site 291
Vác, Hungary
Research Site 457
Hyderabad, India
Research Site 456
Nashik, India
Research Site 451
New Delhi, India
Research Site 303
Ashkelon, Israel
Research Site 305
Jerusalem, Israel
Research Site 307
Petah Tikva, Israel
Research Site 308
Ramat Gan, Israel
Research Site 301
Rehovot, Israel
Research Site 304
Safed, Israel
Research Site 319
Bologna, Italy
Research Site 321
Chieti, Italy
Research Site 322
Genova, Italy
Research Site 320
Messina, Italy
Research Site 315
Milan, Italy
Research Site 314
Montichiari, Italy
Research Site 316
Napoli, Italy
Research Site 317
Napoli, Italy
Research Site 311
Reggio Calabria, Italy
Research Site 318
Roma, Italy
Research Site 312
Salerno, Italy
Research Site 313
Verona, Italy
Research Site 133
Aguascalientes, Mexico
Research Site 134
Culiacán, Mexico
Research Site 534
Hoorn, Netherlands
Research Site 531
Nieuwegein, Netherlands
Research Site 535
Rotterdam, Netherlands
Research Site 532
Sittard-Geleen, Netherlands
Research Site 332
Bydgoszcz, Poland
Research Site 335
Gdansk, Poland
Research Site 336
Katowice, Poland
Research Site 340
Knurów, Poland
Research Site 339
Lodz, Poland
Research Site 337
Lublin, Poland
Research Site 331
Oświęcim, Poland
Research Site 338
Rzeszów, Poland
Research Site 341
Warsaw, Poland
Research Site 342
Warsaw, Poland
Research Site 365
Barnaul, Russia
Research Site 355
Kaluga, Russia
Research Site 358
Kazan', Russia
Research Site 354
Kirov, Russia
Research Site 363
Krasnoyarsk, Russia
Research Site 353
Moscow, Russia
Research Site 359
Moscow, Russia
Research Site 352
Nizhny Novgorod, Russia
Research Site 367
Perm, Russia
Research Site 362
Pyatigorsk, Russia
Research Site 356
Saint Petersburg, Russia
Research Site 369
Saint Petersburg, Russia
Research Site 360
Saratov, Russia
Research Site 361
Smolensk, Russia
Research Site 370
Tomsk, Russia
Research Site 351
Ufa, Russia
Research Site 357
Ulyanovsk, Russia
Research Site 366
Yaroslavl, Russia
Research Site 368
Yekaterinburg, Russia
Research Site 382
Belgrade, Serbia
Research Site 383
Belgrade, Serbia
Research Site 385
Belgrade, Serbia
Research Site 389
Kragujevac, Serbia
Research Site 390
Niš, Serbia
Research Site 388
Novi Sad, Serbia
Research Site 384
Užice, Serbia
Research Site 381
Valjevo, Serbia
Research Site 462
Goyang-si, South Korea
Research Site 461
Seoul, South Korea
Research Site 463
Seoul, South Korea
Research Site 464
Seoul, South Korea
Research Site 465
Seoul, South Korea
Research Site 466
Seoul, South Korea
Research Site 467
Seoul, South Korea
Research Site 406
Barcelona, Spain
Research Site 407
Barcelona, Spain
Research Site 405
Cadiz, Spain
Research Site 402
Donostia / San Sebastian, Spain
Research Site 401
Lleida, Spain
Research Site 403
Madrid, Spain
Research Site 408
Madrid, Spain
Research Site 409
Madrid, Spain
Research Site 411
Pozuelo de Alarcón, Spain
Research Site 410
Salt, Spain
Research Site 404
Seville, Spain
Research site 713
Kaohsiung City, Taiwan
Research Site 711
Taichung, Taiwan
Research site 714
Taipei, Taiwan
Research site 715
Taipei, Taiwan
Research Site 432
Chernivtsi, Ukraine
Research Site 425
Kharkiv, Ukraine
Research Site 429
Kharkiv, Ukraine
Research Site 430
Kharkiv, Ukraine
Research Site 435
Kharkiv, Ukraine
Research Site 436
Kharkiv, Ukraine
Research Site 437
Kharkiv, Ukraine
Research Site 422
Kropyvnytskyi, Ukraine
Research Site 438
Kyiv, Ukraine
Research Site 426
Lviv, Ukraine
Research Site 424
Odesa, Ukraine
Research Site 423
Poltava, Ukraine
Research Site 427
Sumy, Ukraine
Research Site 431
Vinnytsia, Ukraine
Research Site 421
Zaporizhzhia, Ukraine
Research Site 428
Zaporizhzhia, Ukraine
Research Site 544
Exeter, United Kingdom
Research Site 549
Glasgow, United Kingdom
Research Site 552
Newcastle, United Kingdom
Research Site 547
Swansea, United Kingdom
Related Publications (1)
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.
PMID: 39307151RESULT
Related Links
MeSH Terms
Interventions
Limitations and Caveats
The Final Analysis represents the analysis of the cumulative data collected up to the Primary Analysis trigger and beyond through DBE up to the final database lock. Therefore, the endpoints were evaluated considering a time period from the start of DBTP to the end of the DBE Period.
Results Point of Contact
- Title
- Communication Center
- Organization
- Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Study Officials
- STUDY DIRECTOR
Medical Responsible
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 6, 2020
First Posted
April 8, 2020
Study Start
June 12, 2020
Primary Completion
October 2, 2023
Study Completion
March 8, 2024
Last Updated
June 12, 2025
Results First Posted
June 12, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
- Access Criteria
- Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21