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)

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

• Belarus
  • Gomel, Belarus
    • Research Site 144
  • Grodno, Belarus
    • Research Site 143
  • Minsk, Belarus
    • Research Site 142
  • Vitebsk, Belarus
    • Research Site 141
  • Vitebsk, Belarus
    • Research Site 145
• Brazil
  • Belo Horizonte, Brazil
    • Research Site 603
  • Curitiba, Brazil
    • Research Site 599
  • Goiânia, Brazil
    • Research Site 604
  • Joinville, Brazil
    • Research Site 600
  • Passo Fundo, Brazil
    • Research Site 614
  • Porto Alegre, Brazil
    • Research Site 591
  • Porto Alegre, Brazil
    • Research Site 594
  • Porto Alegre, Brazil
    • Research Site 596
  • Vitória, Brazil
    • Research Site 609
• Bulgaria
  • Blagoevgrad, Bulgaria
    • Research Site 155
  • Dupnitsa, Bulgaria
    • Research Site 156
  • Pleven, Bulgaria
    • Research Site 157
  • Pleven, Bulgaria
    • Research Site 801
  • Pleven, Bulgaria
    • Research Site 804
  • Plovdiv, Bulgaria
    • Research Site 805
  • Sofia, 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
  • Veliko Tarnovo, Bulgaria
    • Research Site 154
• Canada
  • Burnaby, Canada
    • Research Site 106
  • London, Canada
    • Research Site 107
  • Montreal, Canada
    • Research Site 105
  • Ottawa, Canada
    • Research Site 101
• France
  • Bordeaux Cedex, France
    • Research Site 455
  • Brest cedex 2, France
    • Research Site 459
  • Clermont Ferrand Cedex, France
    • Reserach Site 451
  • Limoges cedex, France
    • Research Site 458
  • Nimes, France
    • Research Site 456
  • Paris, France
    • Research Site 453
  • Pringy cedex, France
    • Research Site 457
  • Strasbourg cedex, France
    • Research Site 452
  • Tours cedex 9, France
    • Research Site 454
• Germany
  • Augsburg, Germany
    • Research Site 172
  • Berlin, Germany
    • Research Site 177
  • Berlin, Germany
    • Research Site 180
  • Bonn, Germany
    • Research Site 178
  • Dresden, Germany
    • Research Site 184
  • Hamburg, Germany
    • Research Site 174
  • Heidelberg, Germany
    • Research Site 182
  • Koeln, Germany
    • Research Site 179
  • Leipzig, Germany
    • Research Site 181
  • Mainz, Germany
    • Research Site 173
  • Minden, Germany
    • Research Site 176
  • Regensburg, Germany
    • Research Site 171
  • Rostock, Germany
    • Research Site 183
  • Tuebingen, Germany
    • Research Site 175
• Greece
  • Athens, Greece
    • 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
  • Heraklion, Greece
    • Research Site 198
  • Ioannina, Greece
    • Research Site 204
  • Larissa, Greece
    • Research Site 192
  • Marousi, Greece
    • Research Site 199
  • Patra, Greece
    • Research Site 203
  • Patras, Greece
    • Research Site 191
  • Thessaloniki, Greece
    • Research Site 195
• India
  • Ahmedabad, India
    • Research Site 445
  • Bangalore, India
    • Research Site 444
  • Mangalore, India
    • Research Site 443
  • New Delhi, India
    • Research Site 442
• Italy
  • Bari, Italy
    • Research Site 218
  • Catania, Italy
    • Research Site 216
  • Cefalù, Italy
    • Research Site 214
  • Firenze, Italy
    • Research Site 219
  • Milano, Italy
    • Research Site 221
  • Napoli, Italy
    • Research Site 211
  • Napoli, Italy
    • Research Site 215
  • Orbassano, Italy
    • Research Site 220
  • Palermo, Italy
    • Research Site 217
  • Pozzilli, Italy
    • Research Site 212
  • Roma, Italy
    • Research Site 213
  • Roma, Italy
    • Research Site 222
• Latvia
  • Riga, Latvia
    • Research Site 231
  • Riga, Latvia
    • Research Site 232
  • Riga, Latvia
    • Research Site 233
• Lithuania
  • Kaunas, Lithuania
    • Research Site 241
  • Klaipeda, Lithuania
    • Research Site 244
  • Siauliai, Lithuania
    • Research Site 243
  • Vilnius, Lithuania
    • Research Site 242
• Malaysia
  • Kuala Lumpur, Malaysia
    • Research Site 551
  • Kuala Lumpur, Malaysia
    • Research Site 554
  • Kuala Lumpur, Malaysia
    • Research Site 556
  • Kuching, Malaysia
    • Research Site 552
  • Seberang Jaya, Malaysia
    • Research Site 553
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Research Site 251
  • Chisinau, Moldova, Republic of
    • Research Site 252
• Norway
  • Bergen, Norway
    • Research Site 481
  • Drammen, Norway
    • Research site 483
  • Namsos, Norway
    • Research Site 482
• Philippines
  • Baguio City, Philippines
    • Research Site 562
  • Cebu City, Philippines
    • Research Site 561
• Poland
  • Bydgoszcz, Poland
    • Reserach Site 267
  • Bydgoszcz, Poland
    • Reserach Site 268
  • Katowice, Poland
    • Research Site 273
  • Katowice, Poland
    • Research site 846
  • Katowice-Ochojec, Poland
    • Research Site 274
  • Krakow, Poland
    • Research Site 276
  • Lodz, Poland
    • Research Site 263
  • Nowa Sol, Poland
    • Research Site 266
  • Poznan, Poland
    • Research Site 270
  • Rzeszow, Poland
    • Research Site 262
  • Siemianowice, Poland
    • Research Site 265
  • Szczecin, Poland
    • Research Site 271
  • Warszawa, Poland
    • Research Site 264
  • Warszawa, Poland
    • Research Site 277
  • Warszawa, Poland
    • Reserach Site 275
  • Zabrze, Poland
    • Research Site 261
  • Zamosc, Poland
    • Research Site 278
  • Łódź, Poland
    • Research Site 272
• Portugal
  • Aveiro, Portugal
    • Research Site 293
  • Braga, Portugal
    • Research Site 282
  • Coimbra, Portugal
    • Research Site 289
  • Lisboa, Portugal
    • Research Site 281
  • Lisboa, Portugal
    • Research Site 283
  • Lisboa, Portugal
    • Research Site 287
  • Matosinhos, Portugal
    • Research Site 284
  • Porto, Portugal
    • Research Site 292
  • Pragal, Portugal
    • Research Site 288
  • Santa Maria da Feira, Portugal
    • Research Site 291
  • Torres Vedras, Portugal
    • Research Site 286
• Puerto Rico
  • Guaynabo, Puerto Rico
    • Research Site 791
• Romania
  • Brasov, Romania
    • Research Site 314
  • București, Romania
    • Research Site 307
  • Caracal, Romania
    • Research Site 309
  • Targu Mures, Romania
    • Research Site 302
• Russian Federation
  • Kazan, Russian Federation
    • Research Site 325
  • Kazan, Russian Federation
    • Research Site 329
  • Kemerovo, Russian Federation
    • Research Site 323
  • Kirov, Russian Federation
    • Research Site 344
  • Krasnodar, Russian Federation
    • Research Site 340
  • Krasnoyarsk, Russian Federation
    • Research Site 334
  • Moscow, Russian Federation
    • Research Site 341
  • Moscow, Russian Federation
    • Research Site 343
  • Moscow, Russian Federation
    • Research Site 345
  • Nizhniy Novgorod, Russian Federation
    • Research Site 332
  • Novosibirsk, Russian Federation
    • Research Site 327
  • Novosibirsk, Russian Federation
    • Research Site 330
  • Novosibirsk, Russian Federation
    • Research Site 331
  • Novosibirsk, Russian Federation
    • Research Site 335
  • Rostov-on-Don, Russian Federation
    • Research Site 328
  • Saint Petersburg, Russian Federation
    • Research Site 346
  • Saint-Petersburg, Russian Federation
    • Research Site 324
  • Saint-Petersburg, Russian Federation
    • Research Site 338
  • Saint-Petersburg, Russian Federation
    • Research Site 339
  • Saint-Petersburg, Russian Federation
    • Research Site 342
  • Saransk, Russian Federation
    • Research Site 326
  • Sestroretsk, Russian Federation
    • Research Site 321
  • Tyumen, Russian Federation
    • Research Site 337
• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Research Site 493
• Singapore
  • Singapore, Singapore
    • Research Site 571
  • Singapore, Singapore
    • Research Site 572
• Slovakia
  • Banska Bystrica, Slovakia
    • Research Site 351
  • Bratislava, Slovakia
    • Research Site 352
  • Bratislava, Slovakia
    • Research Site 353
  • Bratislava, Slovakia
    • Research Site 354
  • Bratislava, Slovakia
    • Research Site 356
  • Dubnica nad Vahom, Slovakia
    • Research Site 359
  • Trencin, Slovakia
    • Research Site 358
  • Trnava, Slovakia
    • Research Site 357
• Slovenia
  • Celje, Slovenia
    • Research Site 373
  • Ljubljana, Slovenia
    • Research Site 372
  • Maribor, Slovenia
    • Research Site 371
• South Africa
  • Cape Town, South Africa
    • Research Site 501
  • Cape Town, South Africa
    • Research Site 502
  • Cape Town, South Africa
    • Research Site 503
  • Pretoria, South Africa
    • Research Site 504
• Spain
  • Alcorcon, Spain
    • Research Site 384
  • Barakaldo, Spain
    • Research Site 391
  • Barcelona, Spain
    • Research Site 390
  • Cordoba, Spain
    • Research Site 382
  • El Palmar, Spain
    • Research Site 389
  • Madrid, Spain
    • Research Site 388
  • Majadahonda, Spain
    • Research Site 392
  • Malaga, Spain
    • Research Site 383
  • Sevilla, Spain
    • Research Site 387
  • Valencia, Spain
    • Research Site 385
  • Valencia, Spain
    • Research Site 386
  • Vigo, Spain
    • Research Site 381
• Sweden
  • Göteborg, Sweden
    • Research Site 512
  • Malmö, Sweden
    • Research site 514
  • Stockholm, Sweden
    • Research Site 511
  • Uppsala, Sweden
    • Research Site 513
• Switzerland
  • Aarau, Switzerland
    • Research Site 404
  • Bern, Switzerland
    • Research Site 402
  • Lugano, Switzerland
    • Research Site 403
• Thailand
  • Bangkoknoi, Thailand
    • Research Site 583
  • Muang, Thailand
    • Research Site 582
• Turkey
  • Ankara, Turkey
    • Research Site 538
  • Ankara, Turkey
    • Research Site 544
  • Istanbul, Turkey
    • Research Site 531
  • Istanbul, Turkey
    • Research Site 534
  • Istanbul, Turkey
    • Research Site 536
  • Istanbul, Turkey
    • Research Site 541
  • Istanbul, Turkey
    • Research Site 543
  • Izmir, Turkey
    • Research Site 539
  • Kocaeli, Turkey
    • Research Site 533
  • Konya, Turkey
    • Research Site 537
  • Mersin, Turkey
    • Research Site 540
  • Samsun, Turkey
    • Research Site 535
  • Trabzon, Turkey
    • Research Site 532
• Ukraine
  • Chernihiv, Ukraine
    • Research Site 415
  • Chernihiv, Ukraine
    • Research Site 417
  • Dnipro, Ukraine
    • Research Site 414
  • Dnipro, Ukraine
    • Research Site 416
  • Dnipro, Ukraine
    • Research Site 420
  • Ivano-Frankivsk, Ukraine
    • Research Site 413
  • Kharkiv, Ukraine
    • Research Site 624
  • Kharkiv, Ukraine
    • Research Site 632
  • Kharkiv, Ukraine
    • Research Site 633
  • Kherson, Ukraine
    • Research Site 419
  • Kyiv, Ukraine
    • Research Site 411
  • Kyiv, Ukraine
    • Research Site 418
  • Lutsk, Ukraine
    • Research Site 629
  • Lviv, Ukraine
    • Research Site 627
  • Poltava, Ukraine
    • Research Site 622
  • Rivne, Ukraine
    • Research Site 625
  • Ternopil, Ukraine
    • Research Site 628
  • Uzhgorod, Ukraine
    • Research Site 630
  • Vinnytsia, Ukraine
    • Research Site 623
  • Zaporizhzhia, Ukraine
    • Research Site 412
  • Zaporizhzhia, Ukraine
    • Research Site 621
  • Zaporizhzhia, Ukraine
    • Research Site 631
  • Zhytomyr, Ukraine
    • Research Site 626
• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • Research Site 752
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Research Site 741
    • Tucson, Arizona, United States, 85710
      • Research Site 704
  • California
    • Hanford, California, United States, 93230
      • Research Site 751
    • West Hollywood, California, United States, 90048
      • Research Site 737
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Research Site 759
    • Fort Collins, Colorado, United States, 80528
      • Research Site 725
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Research Site 746
    • Jacksonville, Florida, United States, 32209
      • Research Site 718
    • Naples, Florida, United States, 34105
      • Research Site 702
    • Orlando, Florida, United States, 32806
      • Research Site 740
    • Port Charlotte, Florida, United States, 33952
      • Research Site 726
    • Sarasota, Florida, United States, 34243
      • Research Site 719
    • Tampa, Florida, United States, 33612
      • Research Site 743
    • Tampa, Florida, United States, 33634
      • Research Site 707
    • Vero Beach, Florida, United States, 32960
      • Research Site 732
    • Weeki Wachee, Florida, United States, 34607
      • Research Site 705
    • West Palm Beach, Florida, United States, 33407
      • Research Site 753
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Research Site 742
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Research site 715
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Research site 714
    • Lafayette, Indiana, United States, 47904
      • Research Site 744
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • Research Site 717
  • Kentucky
    • Nicholasville, Kentucky, United States, 40356
      • Research Site 735
  • Maine
    • Scarborough, Maine, United States, 04074
      • Research Site 706
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Site 738
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Research Site 723
  • New York
    • Amherst, New York, United States, 14226
      • Research Site 724
  • North Carolina
    • Asheville, North Carolina, United States, 28006
      • Research Site 736
    • Chapel Hill, North Carolina, United States, 27599
      • Research Site 712
    • Winston-Salem, North Carolina, United States, 27157
      • Research Site 728
  • Ohio
    • Canton, Ohio, United States, 44735
      • Research Site 711
    • Columbus, Ohio, United States, 43214
      • Research Site 757
    • Dayton, Ohio, United States, 45459
      • Research Site 734
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Research Site 748
  • Texas
    • San Antonio, Texas, United States, 78258
      • Research Site 703
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Research Site 721

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): July 2, 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 3, 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_0082; 2019-004980-36 (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