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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Evobrutinib; Drug: Placebo (match to Teriflunomide); Drug: Teriflunomide; Drug: Placebo (match to Evobrutinib)

• Study Type: Interventional
• Enrollment (Actual): 1124
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma 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 de Buenos Aires, Argentina
    • Research Site 561
  • Ciudad Autonoma de Buenos Aires, Argentina
    • Research Site 562
  • Ciudad Autonoma de Buenos Aires, Argentina
    • Research Site 577
  • Cordoba, Argentina
    • Research Site 564
  • Godoy Cruz, Argentina
    • Research Site 568
  • Guaymallen, Argentina
    • Research Site 576
  • Rosario, Argentina
    • Research Site 565
  • Rosario, Argentina
    • Research Site 569
  • Salta, Argentina
    • Research Site 571
  • San Juan, Argentina
    • Research Site 572
  • San Miguel de Tucuman, Argentina
    • Research Site 563
• Australia
  • Auchenflower, Australia
    • Research Site 104
  • Concord, Australia
    • Research Site 107
  • Hobart, Australia
    • Research Site 109
  • Liverpool, Australia
    • Research Site 101
  • New Lambton Heights, Australia
    • Research Site 102
  • St Leonards, Australia
    • Research Site 103
• Austria
  • Innsbruck, Austria
    • Research Site 151
  • Linz, Austria
    • Research Site 156
  • Salzburg, Austria
    • Research Site 154
  • Vienna, Austria
    • Research Site 153
• Belgium
  • Bruxelles, Belgium
    • Research Site 474
  • Bruxelles, Belgium
    • Research Site 475
  • Kortrijk, Belgium
    • Research Site 473
  • La Louvière, Belgium
    • Research Site 471
  • Liège, Belgium
    • Research Site 472
  • Overpelt, Belgium
    • Research Site 478
  • Roeselare, Belgium
    • Research Site 476
• Bosnia and Herzegovina
  • Bihac, Bosnia and Herzegovina
    • Research Site 161
  • Mostar, Bosnia and Herzegovina
    • Research Site 163
  • Sarajevo, Bosnia and Herzegovina
    • Research Site 162
• Bulgaria
  • Pleven, Bulgaria
    • Research Site 171
  • Pleven, Bulgaria
    • Research Site 174
  • Plovdiv, Bulgaria
    • Reasearch Site 175
  • Plovdiv, Bulgaria
    • Research Site 177
  • Sofia, 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
• Canada
  • Greenfield Park, Canada
    • Research Site 126
  • Levis, Canada
    • Research Site 125
  • Moncton, Canada
    • Research Site 128
  • Montreal, Canada
    • Research Site 129
  • Toronto, Canada
    • Research Site 124
• Colombia
  • Barranquilla, Colombia
    • Research Site 591
  • Barranquilla, Colombia
    • Research Site 597
  • Medellin, Colombia
    • Research Site 592
  • Medellin, Colombia
    • Research Site 600
• Croatia
  • Osijek, Croatia
    • Research Site 193
  • Rijeka, Croatia
    • Research Site 197
  • Varazdin, Croatia
    • Research Site 195
  • Zagreb, Croatia
    • Research Site 192
  • Zagreb, Croatia
    • Research Site 194
• Czechia
  • Brno, Czechia
    • Research Site 212
  • Brno, Czechia
    • Research Site 218
  • Hradec Kralove, Czechia
    • Research Site 219
  • Hradec Kralove, Czechia
    • Research Site 222
  • Jihlava, Czechia
    • Research Site 211
  • Ostrava, Czechia
    • Research Site 223
  • Pardubice, Czechia
    • Research Site 215
  • Plzen-Bory, Czechia
    • Research Site 216
  • Praha 10, Czechia
    • Research Site 217
  • Praha 2, Czechia
    • Research Site 220
  • Praha 4 - Krc, Czechia
    • Research Site 213
  • Praha 5, Czechia
    • Research Site 224
• Estonia
  • Tallinn, Estonia
    • Research Site 231
  • Tartu, Estonia
    • Research Site 232
• Finland
  • Turku, Finland
    • Research Site 491
• France
  • Bron cedex, France
    • Research Site 510
  • Caen cedex 9, France
    • Research Site 509
  • Grenoble cedex 09, France
    • Research Site 502
  • Lille, France
    • Research Site 508
  • Lille cedex, France
    • Research Site 504
  • Montpellier, France
    • Reserach Site 505
  • Nantes cedex 1, France
    • Research Site 511
  • Nice Cedex 1, France
    • Research Site 506
  • Rennes cedex 09, France
    • Research Site 507
  • Rouen Cedex, France
    • Research Site 501
  • Toulouse cedex 9, France
    • Research Site 503
• Georgia
  • Tbilisi, Georgia
    • 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
• Germany
  • Bamberg, Germany
    • Research Site 265
  • Bayreuth, Germany
    • Research Site 267
  • Berlin, Germany
    • Research Site 271
  • Bochum, Germany
    • Research Site 264
  • Bonn, Germany
    • Research Site 274
  • Erbach, Germany
    • Research Site 270
  • Essen, Germany
    • Research Site 268
  • Frankfurt, Germany
    • Research Site 263
  • Hannover, Germany
    • Research Site 275
  • Mannheim, Germany
    • Research Site 272
  • Muenchen, Germany
    • Research Site 262
  • Muenster, Germany
    • Research Site 266
  • Potsdam, Germany
    • Research Site 261
  • Siegen, Germany
    • Research Site 273
  • Ulm, Germany
    • Research Site 269
• Hong Kong
  • Hong Kong, Hong Kong
    • Research Site 700
  • Hongkong, Hong Kong
    • Research Site 704
  • Shatin, Hong Kong
    • Research Site 701
• Hungary
  • Budapest, Hungary
    • Research Site 282
  • Budapest, Hungary
    • Research Site 285
  • Budapest, Hungary
    • Research Site 286
  • Budapest, Hungary
    • Research Site 288
  • Budapest, Hungary
    • Research Site 290
  • Kistarcsa, Hungary
    • Research Site 281
  • Pecs, Hungary
    • Research Site 284
  • Tatabanya, Hungary
    • Research Site 289
  • Vac, Hungary
    • Research Site 291
• India
  • Hyderabad, India
    • Research Site 457
  • Nashik, India
    • Research Site 456
  • New Delhi, India
    • Research Site 451
• Israel
  • Ashkelon, Israel
    • Research Site 303
  • Jerusalem, Israel
    • Research Site 305
  • Petah Tikva, Israel
    • Research Site 307
  • Ramat Gan, Israel
    • Research Site 308
  • Rechovot, Israel
    • Research Site 301
  • Safed, Israel
    • Research Site 304
• Italy
  • Bologna, Italy
    • Research Site 319
  • Chieti, Italy
    • Research Site 321
  • Genova, Italy
    • Research Site 322
  • Messina, Italy
    • Research Site 320
  • Milano, Italy
    • Research Site 315
  • Montichiari, Italy
    • Research Site 314
  • Napoli, Italy
    • Research Site 316
  • Napoli, Italy
    • Research Site 317
  • Reggio Calabria, Italy
    • Research Site 311
  • Roma, Italy
    • Research Site 318
  • Salerno, Italy
    • Research Site 312
  • Verona, Italy
    • Research Site 313
• Korea, Republic of
  • Goyang-si, Korea, Republic of
    • Research Site 462
  • Seoul, Korea, Republic of
    • Research Site 461
  • Seoul, Korea, Republic of
    • Research Site 463
  • Seoul, Korea, Republic of
    • Research Site 464
  • Seoul, Korea, Republic of
    • Research Site 465
  • Seoul, Korea, Republic of
    • Research Site 466
  • Seoul, Korea, Republic of
    • Research Site 467
• Mexico
  • Aguascalientes, Mexico
    • Research Site 133
  • Culiacan, Mexico
    • Research Site 134
• Netherlands
  • Hoorn, Netherlands
    • Research Site 534
  • Nieuwegein, Netherlands
    • Research Site 531
  • Rotterdam, Netherlands
    • Research Site 535
  • Sittard-Geleen, Netherlands
    • Research Site 532
• Poland
  • Bydgoszcz, Poland
    • Research Site 332
  • Gdansk, Poland
    • Research Site 335
  • Katowice, Poland
    • Research Site 336
  • Knurow, Poland
    • Research Site 340
  • Lodz, Poland
    • Research Site 339
  • Lublin, Poland
    • Research Site 337
  • Oswiecim, Poland
    • Research Site 331
  • Rzeszów, Poland
    • Research Site 338
  • Warszawa, Poland
    • Research Site 341
  • Warszawa, Poland
    • Research Site 342
• Russian Federation
  • Barnaul, Russian Federation
    • Research Site 365
  • Ekaterinburg, Russian Federation
    • Research Site 368
  • Kaluga, Russian Federation
    • Research Site 355
  • Kazan, Russian Federation
    • Research Site 358
  • Kirov, Russian Federation
    • Research Site 354
  • Krasnoyarsk, Russian Federation
    • Research Site 363
  • Moscow, Russian Federation
    • Research Site 353
  • Moscow, Russian Federation
    • Research Site 359
  • Nizhniy Novgorod, Russian Federation
    • Research Site 352
  • Perm, Russian Federation
    • Research Site 367
  • Pyatigorsk, Russian Federation
    • Research Site 362
  • Saint-Petersburg, Russian Federation
    • Research Site 369
  • Saratov, Russian Federation
    • Research Site 360
  • Smolensk, Russian Federation
    • Research Site 361
  • St.Petersburg, Russian Federation
    • Research Site 356
  • Tomsk, Russian Federation
    • Research Site 370
  • Ufa, Russian Federation
    • Research Site 351
  • Ulyanovsk, Russian Federation
    • Research Site 357
  • Yaroslavl, Russian Federation
    • Research Site 366
• Serbia
  • Belgrade, Serbia
    • Research Site 382
  • Belgrade, Serbia
    • Research Site 383
  • Belgrade, Serbia
    • Research Site 385
  • Kragujevac, Serbia
    • Research Site 389
  • Nis, Serbia
    • Research Site 390
  • Novi Sad, Serbia
    • Research Site 388
  • Uzice, Serbia
    • Research Site 384
  • Valjevo, Serbia
    • Research Site 381
• Spain
  • Barcelona, Spain
    • Research Site 406
  • Barcelona, Spain
    • Research Site 407
  • Cadiz, Spain
    • Research Site 405
  • Lleida, Spain
    • Research Site 401
  • Madrid, Spain
    • Research Site 403
  • Madrid, Spain
    • Research Site 408
  • Madrid, Spain
    • Research Site 409
  • Pozuelo de Alarcon, Spain
    • Research Site 411
  • Salt, Spain
    • Research Site 410
  • San Sebastian, Spain
    • Research Site 402
  • Sevilla, Spain
    • Research Site 404
• Taiwan
  • Kaohsiung, Taiwan
    • Research site 713
  • Taichung, Taiwan
    • Research Site 711
  • Taipei, Taiwan
    • Research site 714
  • Taipei, Taiwan
    • Research site 715
• Ukraine
  • Chernivtsi, Ukraine
    • Research Site 432
  • Kharkiv, 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
  • Kropyvnytskyi, Ukraine
    • Research Site 422
  • Kyiv, Ukraine
    • Research Site 438
  • Lviv, Ukraine
    • Research Site 426
  • Odesa, Ukraine
    • Research Site 424
  • Poltava, Ukraine
    • Research Site 423
  • Sumy, Ukraine
    • Research Site 427
  • Vinnytsia, Ukraine
    • Research Site 431
  • Zaporizhzhia, Ukraine
    • Research Site 421
  • Zaporizhzhia, Ukraine
    • Research Site 428
• United Kingdom
  • Exeter, United Kingdom
    • Research Site 544
  • Glasgow, United Kingdom
    • Research Site 549
  • Newcastle, United Kingdom
    • Research Site 552
  • Swansea, United Kingdom
    • Research Site 547
• United States
  • Alabama
    • Mobile, Alabama, United States, 36693-7003
      • Research Site 629
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Research Site 614
    • Phoenix, Arizona, United States, 85018
      • Research Site 677
  • California
    • Long Beach, California, United States, 90806
      • Research Site 642
    • Pasadena, California, United States, 91105
      • Research Site 644
    • San Diego, California, United States, 92121
      • Research Site 672
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • Research Site 634
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Research Site 656
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Research Site 616
    • Maitland, Florida, United States, 32751
      • Research Site 625
    • Miami, Florida, United States, 33136
      • Research Site 617
    • Ormond Beach, Florida, United States, 32174
      • Research Site 643
    • Saint Petersburg, Florida, United States, 33713
      • Research site 645
    • Tallahassee, Florida, United States, 32308
      • Research Site 652
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Research Site 621
    • Northbrook, Illinois, United States, 60062
      • Research Site 649
    • Peoria, Illinois, United States, 61637
      • Research Site 675
    • Rolling Meadows, Illinois, United States, 60008
      • Research Site 628
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Research Site 624
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Research Site 632
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Research Site 653
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Research Site 623
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site 633
    • Foxboro, Massachusetts, United States, 02035
      • Research Site 639
    • Lawrence, Massachusetts, United States, 01843
      • Research Site 635
    • Worcester, Massachusetts, United States, 01655
      • Research Site 636
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site 613
    • Farmington Hills, Michigan, United States, 48334
      • Research Site 612
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Research Site 638
    • Saint Louis, Missouri, United States, 63131
      • Research Site 664
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Site 668
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Research Site 626
  • New Jersey
    • Audubon, New Jersey, United States, 08106
      • Research Site 667
  • New York
    • Patchogue, New York, United States, 11772
      • Research Site 620
  • Ohio
    • Akron, Ohio, United States, 44320
      • Research Site 663
    • Toledo, Ohio, United States, 43614-2598
      • Research Site 630
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Research Site 611
    • Oklahoma City, Oklahoma, United States, 73104
      • Research Site 641
  • Oregon
    • Springfield, Oregon, United States, 97477
      • Research Site 615
  • Pennsylvania
    • Willow Grove, Pennsylvania, United States, 19090
      • Research Site 647
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Research Site 648
    • Nashville, Tennessee, United States, 37205
      • Research Site 627
    • Nashville, Tennessee, United States, 37215
      • Research Site 637
  • Texas
    • Dallas, Texas, United States, 75214
      • Research Site 662
    • Houston, Texas, United States, 77030
      • Research Site 631
    • Lubbock, Texas, United States, 79410
      • Research Site 650
    • Round Rock, Texas, United States, 78681
      • Research Site 619
  • Utah
    • Layton, Utah, United States, 84041
      • Research Site 676
  • Virginia
    • Alexandria, Virginia, United States, 22310
      • Research Site 673
    • Virginia Beach, Virginia, United States, 23456
      • Research Site 654
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3596
      • Research Site 651

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Evobrutinib + Teriflunomide matched Placebo: DB Period	Drug: Evobrutinib; Evobrutinib twice daily (BID) in DBTP.; Other Names: M2951; Drug: Placebo (match to Teriflunomide); Placebo match to Teriflunomide once daily in DBTP.
Active Comparator: Teriflunomide + Evobrutinib matched Placebo: DB Period	Drug: Teriflunomide; Teriflunomide once daily in DBTP.; Drug: Placebo (match to Evobrutinib); Placebo match to Evobrutinib BID in DBTP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OLE Period: Number of Participants with Adverse Events and Serious Adverse Events (SAE)s		Baseline OLE up to 96 weeks
DBTP: Annualized Relapse Rate (ARR)	The annualized relapse rates up to 156 weeks will be calculated based on qualified relapses. Qualifying relapse is defined as occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than 24 hours, no fever, infection, injury, adverse events, and preceded by a stable or improving neurological state for greater than or equal to (=>) 30 days).	Up to 156 weeks
DBE Period: ARR	The annualized relapse rates up to 96 weeks will be calculated based on qualified relapses. Qualifying relapse is defined as occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis (MS) (for more than 24 hours, no fever, infection, injury, adverse events, and preceded by a stable or improving neurological state for greater than or equal to (=>) 30 days).	Up to 96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OLE Period: Time to first occurrence of 24-week CDP as measured by EDSS		Baseline OLE up to 96 weeks
OLE Period: Time to first occurrence of 24-week CDI as measured by EDSS		Baseline OLE up to 96 weeks
OLE Period: Symbol Digital Modalities Test Over time		Baseline OLE up to 96 weeks
OLE Period: PROMISnq PF (MS) 15a score change over time		Baseline OLE up to 96 weeks
OLE Period: PROMIS Fatigue (MS) 8a Score Change Over Time		Baseline OLE up to 96 weeks
OLE Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Electrocardiogram (ECG) and Laboratory Findings		Baseline OLE up to 96 weeks
OLE: Total Number of New or Enlarging T2 Lesions Assessed on the Last Available Magnetic Resonance Imaging (MRI) Scans		Baseline OLE up to 96 weeks
OLE: Change from Baseline in T2 lesion Volume Over Time		Baseline OLE up to 96 weeks
DBTP: Time to First Occurrence of 12-Week Confirmed Disability Progression (CDP) as measured by Expanded Disability Status Scale (EDSS) Progression		Up to 156 weeks
DBTP: Time to First Occurrence of 24-Week CDP as measured by EDSS Progression		Up to 156 weeks
DBTP: Time to First Occurrence of 24-Week Confirmed Disability Improvement (CDI) as measured by EDSS Improvement		Up to 156 weeks
DBTP: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Fatigue Short Form Score		Baseline up to 96 weeks
DBTP: Total Number of Gadolinium-Enhancing (Gd+) T1 Lesions Assessed by all Available Magnetic Resonance Imaging (MRI) Scans		Up to Week 156
DBTP: Neurofilament light chain (NfL) Serum Concentration		At Week 12
DBTP: Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.	Baseline up to 156 weeks
DBTP: Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings	Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported.	Baseline up to 156 weeks
DBTP: Absolute Concentrations of Immunoglobulin (Ig) Levels		Baseline up to 156 weeks
DBTP: Change From Baseline in Immunoglobulin (Ig) Levels		Baseline up to 156 weeks
DBE Period: Time to First Occurrence of 12-Week CDP as measured by EDSS Progression		Up to 96 weeks
DBE Period: Time to First Occurrence of 24-Week CDP as measured by EDSS Progression		Up to 96 weeks
DBE Period: Change From Baseline in PROMIS MS PF Short Form Score		Baseline up to 96 weeks
DBE Period: Change From Baseline in PROMIS MS Fatigue Short Form Score		Baseline up to 96 weeks
DBE Period: Total Number of Gd+ T1 Lesions Assessed by all Available MRI Scans		Up to Week 96
DBE Period: Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)	An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment.	Baseline up to 96 weeks
DBE Period: Number of Participants With Clinically Significant Change From Baseline in Vital Signs, Laboratory Parameters and Electrocardiogram Findings	Number of participants with clinically significant change from baseline in vital signs, laboratory parameters and electrocardiogram findings will be reported.	Baseline up to 96 weeks
DBE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels		Baseline up to 96 weeks
DBE Period: Change From Baseline in Immunoglobulin (Ig) Levels		Baseline up to 96 weeks
OLE Period: ARR based on protocol-defined qualified relapses		Baseline OLE up to 96 weeks
DBTP: Change From Baseline in Patient Reported Outcomes Measurement Information System (PROMIS) MS Physical Function (PF) Short Form Score		Baseline up to 96 weeks
DBTP: Total Number of New or Enlarging T2 Lesions Assessed by the Last Available Magnetic Resonance Imaging (MRI) Scan Relative to Baseline MRI Scan		Up to Week 156
DBE Period: Time to First Occurrence of 24-Week CDI as measured by EDSS Improvement		Up to 96 weeks
DBE Period: Total Number of New or Enlarging T2 Lesions Assessed on the Last Available MRI Scans Relative to Baseline MRI Scan		Up to Week 96

Collaborators and Investigators

• Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
• Collaborators: EMD Serono Research & Development Institute, Inc.
• Investigators: Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• US Medical Information website, Medical Resources
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2020
• Primary Completion (Actual): October 2, 2023
• Study Completion (Estimated): June 26, 2026

Study Registration Dates

• First Submitted: April 6, 2020
• First Submitted That Met QC Criteria: April 6, 2020
• First Posted (Actual): April 8, 2020

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Evobrutinib; Relapsing Multiple Sclerosis; Teriflunomide; Aubagio®
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Teriflunomide
• Other Study ID Numbers: MS200527_0080; 2019-004972-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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
• IPD Sharing 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
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No