Study Stopped
Primary analysis of the RMS phase 3 study (MS200527\_0082) resulted in the early termination of the study.
Study of Evobrutinib in Participants With RMS (evolutionRMS 2)
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 2)
2 other identifiers
interventional
1,166
31 countries
270
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 Jul 2020
Typical duration for phase_3
270 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
July 2, 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 19, 2024
CompletedResults Posted
Study results publicly available
January 14, 2025
CompletedMarch 21, 2025
March 1, 2025
3.3 years
April 6, 2020
October 1, 2024
March 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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).
Baseline up to 170 weeks
Secondary Outcomes (31)
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)
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)
- +26 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.
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.
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 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
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 (278)
Research Site 752
Cullman, Alabama, 35058, United States
Research Site 741
Scottsdale, Arizona, 85258, United States
Research Site 704
Tucson, Arizona, 85710, United States
Research Site 751
Hanford, California, 93230, United States
Research Site 737
West Hollywood, California, 90048, United States
Research Site 759
Colorado Springs, Colorado, 80907, United States
Research Site 725
Fort Collins, Colorado, 80528, United States
Research Site 746
Altamonte Springs, Florida, 32714, United States
Research Site 718
Jacksonville, Florida, 32209, United States
Research Site 702
Naples, Florida, 34105, United States
Research Site 740
Orlando, Florida, 32806, United States
Research Site 726
Port Charlotte, Florida, 33952, United States
Research Site 719
Sarasota, Florida, 34243, United States
Research Site 743
Tampa, Florida, 33612, United States
Research Site 707
Tampa, Florida, 33634, United States
Research Site 732
Vero Beach, Florida, 32960, United States
Research Site 705
Weeki Wachee, Florida, 34607, United States
Research Site 753
West Palm Beach, Florida, 33407, United States
Research Site 742
Honolulu, Hawaii, 96817, United States
Research Site 715
Evanston, Illinois, 60201, United States
Research Site 714
Fort Wayne, Indiana, 46804, United States
Research Site 744
Lafayette, Indiana, 47904, United States
Research Site 717
Overland Park, Kansas, 66212, United States
Research Site 735
Nicholasville, Kentucky, 40356, United States
Research Site 706
Scarborough, Maine, 04074, United States
Research Site 738
Detroit, Michigan, 48202, United States
Research Site 723
St Louis, Missouri, 63128, United States
Research Site 724
Amherst, New York, 14226, United States
Research Site 736
Asheville, North Carolina, 28006, United States
Research Site 712
Chapel Hill, North Carolina, 27599, United States
Research Site 730
Raleigh, North Carolina, 27607, United States
Research Site 728
Winston-Salem, North Carolina, 27157, United States
Research Site 711
Canton, Ohio, 44735, United States
Research Site 757
Columbus, Ohio, 43214, United States
Research Site 734
Dayton, Ohio, 45459, United States
Research Site 748
Philadelphia, Pennsylvania, 19107, United States
Research Site 703
San Antonio, Texas, 78258, United States
Research Site 721
Norfolk, Virginia, 23502, United States
Research Site 143
Grodno, Belarus
Research Site 144
Homyel, Belarus
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, France
Research Site 459
Brest, France
Reserach Site 451
Clermont-Ferrand, France
Research Site 458
Limoges, France
Research Site 456
Nîmes, France
Research Site 453
Paris, France
Research Site 457
Pringy, France
Research Site 452
Strasbourg, France
Research Site 454
Tours, France
Research Site 172
Augsburg, Germany
Research Site 177
Berlin, Germany
Research Site 180
Berlin, Germany
Research Site 178
Bonn, Germany
Research Site 179
Cologne, Germany
Research Site 184
Dresden, Germany
Research Site 174
Hamburg, Germany
Research Site 182
Heidelberg, Germany
Research Site 181
Leipzig, Germany
Research Site 173
Mainz, Germany
Research Site 176
Minden, Germany
Research Site 171
Regensburg, Germany
Research Site 183
Rostock, Germany
Research Site 175
Tübingen, Germany
Research Site 194
Athens, Greece
Research Site 196
Athens, Greece
Research Site 197
Athens, Greece
Research Site 201
Athens, Greece
Research Site 202
Athens, Greece
Research Site 205
Athens, Greece
Research Site 207
Athens, Greece
Reserach Site 206
Athens, Greece
Research Site 198
Heraklion, Greece
Research Site 204
Ioannina, Greece
Research Site 192
Larissa, Greece
Research Site 199
Marousi, Greece
Research Site 191
Pátrai, Greece
Research Site 203
Pátrai, Greece
Research Site 195
Thessaloniki, Greece
Research Site 445
Ahmedabad, India
Research Site 444
Bangalore, India
Research Site 443
Mangalore, India
Research Site 442
New Delhi, India
Research Site 218
Bari, Italy
Research Site 216
Catania, Italy
Research Site 214
Cefalù, Italy
Research Site 219
Florence, Italy
Research Site 221
Milan, Italy
Research Site 211
Napoli, Italy
Research Site 215
Napoli, Italy
Research Site 220
Orbassano, Italy
Research Site 217
Palermo, Italy
Research Site 212
Pozzilli, Italy
Research Site 213
Roma, Italy
Research Site 222
Roma, Italy
Research Site 231
Riga, Latvia
Research Site 232
Riga, Latvia
Research Site 233
Riga, Latvia
Research site 241
Kaunas, Lithuania
Research site 244
Klaipėda, Lithuania
Research site 243
Šiauliai, Lithuania
Research site 242
Vilnius, Lithuania
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
Research Site 252
Chisinau, Moldova
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 273
Katowice, Poland
Research site 846
Katowice, Poland
Research site 274
Katowice-Ochojec, Poland
Research Site 276
Krakow, Poland
Research Site 263
Lodz, Poland
Research Site 272
Lodz, Poland
Research Site 266
Nowa Sól, Poland
Research Site 270
Poznan, Poland
Research Site 262
Rzeszów, Poland
Research Site 265
Siemianowice Śląskie, Poland
Research Site 271
Szczecin, Poland
Research Site 264
Warsaw, Poland
Research Site 277
Warsaw, Poland
Reserach Site 275
Warsaw, Poland
Research Site 269
Wroclaw, Poland
Research Site 261
Zabrze, Poland
Research Site 278
Zamość, Poland
Research Site 293
Aveiro, Portugal
Research Site 282
Braga, Portugal
Research Site 289
Coimbra, Portugal
Research Site 281
Lisbon, Portugal
Research Site 283
Lisbon, Portugal
Research Site 287
Lisbon, Portugal
Research SIte 284
Matosinhos Municipality, 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
Bucharest, Romania
Research Site 309
Caracal, Romania
Research Site 302
Târgu Mureş, Romania
Research Site 325
Kazan', Russia
Research Site 329
Kazan', Russia
Research Site 323
Kemerovo, Russia
Research Site 344
Kirov, Russia
Research Site 340
Krasnodar, Russia
Research Site 334
Krasnoyarsk, Russia
Research Site 341
Moscow, Russia
Research Site 343
Moscow, Russia
Research Site 345
Moscow, Russia
Research Site 332
Nizhny Novgorod, Russia
Research Site 327
Novosibirsk, Russia
Research Site 330
Novosibirsk, Russia
Research Site 331
Novosibirsk, Russia
Research Site 335
Novosibirsk, Russia
Research Site 328
Rostov-on-Don, Russia
Research Site 324
Saint Petersburg, Russia
Research Site 338
Saint Petersburg, Russia
Research Site 339
Saint Petersburg, Russia
Research Site 342
Saint Petersburg, Russia
Research Site 346
Saint Petersburg, Russia
Research Site 326
Saransk, Russia
Research Site 321
Sestroretsk, Russia
Research Site 337
Tyumen, Russia
Research Site 493
Riyadh, Saudi Arabia
Research Site 571
Singapore, Singapore
Research site 572
Singapore, Singapore
Research Site 351
Banská 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 Váhom, Slovakia
Research Site 358
Trenčín, 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
Alcorcón, Spain
Research Site 391
Barakaldo, Spain
Research Site 390
Barcelona, Spain
Research Site 382
Córdoba, Spain
Research Site 389
El Palmar, Spain
Research Site 388
Madrid, Spain
Research Site 392
Majadahonda, Spain
Research Site 383
Málaga, Spain
Research Site 387
Seville, Spain
Research Site 385
Valencia, Spain
Research Site 386
Valencia, Spain
Research Site 381
Vigo, Spain
Research Site 512
Gothenburg, Sweden
Research site 514
Malmo, Sweden
Research Site 511
Stockholm, Sweden
Research Site 513
Uppsala, Sweden
Research Site 404
Aarau, Switzerland
Research Site 402
Bern, Switzerland
Research Site 403
Lugano, Switzerland
Research Site 583
Bangkoknoi, Thailand
Research Site 582
Muang, Thailand
Research Site 538
Ankara, Turkey (Türkiye)
Research Site 544
Ankara, Turkey (Türkiye)
Research Site 531
Istanbul, Turkey (Türkiye)
Research Site 534
Istanbul, Turkey (Türkiye)
Research Site 536
Istanbul, Turkey (Türkiye)
Research Site 541
Istanbul, Turkey (Türkiye)
Research Site 543
Istanbul, Turkey (Türkiye)
Research Site 539
Izmir, Turkey (Türkiye)
Research Site 533
Kocaeli, Turkey (Türkiye)
Research Site 537
Konya, Turkey (Türkiye)
Research Site 540
Mersin, Turkey (Türkiye)
Research Site 535
Samsun, Turkey (Türkiye)
Research Site 532
Trabzon, Turkey (Türkiye)
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
Uzhhorod, 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
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
July 2, 2020
Primary Completion
October 2, 2023
Study Completion
March 19, 2024
Last Updated
March 21, 2025
Results First Posted
January 14, 2025
Record last verified: 2025-03
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