Study of Evobrutinib in Participants With RMS (evolutionRMS 2)

NCT ID: NCT04338061

Last Updated: 2025-03-21

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

1166 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-02

Study Completion Date

2024-03-19

Brief Summary

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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.

Detailed Description

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Conditions

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Relapsing Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Teriflunomide

Group Type ACTIVE_COMPARATOR

Teriflunomide

Intervention Type DRUG

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.

Evobrutinib

Group Type EXPERIMENTAL

Evobrutinib

Intervention Type DRUG

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.

Interventions

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Teriflunomide

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.

Intervention Type DRUG

Evobrutinib

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.

Intervention Type DRUG

Other Intervention Names

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M2951

Eligibility Criteria

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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 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

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role collaborator

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

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Research Site 752

Cullman, Alabama, United States

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Research Site 741

Scottsdale, Arizona, United States

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Research Site 704

Tucson, Arizona, United States

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Research Site 751

Hanford, California, United States

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Research Site 737

West Hollywood, California, United States

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Research Site 759

Colorado Springs, Colorado, United States

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Research Site 725

Fort Collins, Colorado, United States

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Research Site 746

Altamonte Springs, Florida, United States

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Research Site 718

Jacksonville, Florida, United States

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Research Site 702

Naples, Florida, United States

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Research Site 740

Orlando, Florida, United States

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Research Site 726

Port Charlotte, Florida, United States

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Research Site 719

Sarasota, Florida, United States

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Research Site 743

Tampa, Florida, United States

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Research Site 707

Tampa, Florida, United States

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Research Site 732

Vero Beach, Florida, United States

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Research Site 705

Weeki Wachee, Florida, United States

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Research Site 753

West Palm Beach, Florida, United States

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Research Site 742

Honolulu, Hawaii, United States

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Research Site 715

Evanston, Illinois, United States

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Research Site 714

Fort Wayne, Indiana, United States

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Research Site 744

Lafayette, Indiana, United States

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Research Site 717

Overland Park, Kansas, United States

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Research Site 735

Nicholasville, Kentucky, United States

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Research Site 706

Scarborough, Maine, United States

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Research Site 738

Detroit, Michigan, United States

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Research Site 723

St Louis, Missouri, United States

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Research Site 724

Amherst, New York, United States

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Research Site 736

Asheville, North Carolina, United States

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Research Site 712

Chapel Hill, North Carolina, United States

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Research Site 730

Raleigh, North Carolina, United States

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Research Site 728

Winston-Salem, North Carolina, United States

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Research Site 711

Canton, Ohio, United States

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Research Site 757

Columbus, Ohio, United States

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Research Site 734

Dayton, Ohio, United States

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Research Site 748

Philadelphia, Pennsylvania, United States

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Research Site 703

San Antonio, Texas, United States

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Research Site 721

Norfolk, Virginia, United States

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Research Site 143

Grodno, , Belarus

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Research Site 144

Homyel, , Belarus

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Research Site 142

Minsk, , Belarus

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Research Site 141

Vitebsk, , Belarus

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Research Site 145

Vitebsk, , Belarus

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Research Site 603

Belo Horizonte, , Brazil

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Research Site 599

Curitiba, , Brazil

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Research Site 604

Goiânia, , Brazil

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Research Site 600

Joinville, , Brazil

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Research Site 614

Passo Fundo, , Brazil

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Research Site 591

Porto Alegre, , Brazil

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Research Site 594

Porto Alegre, , Brazil

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Research Site 596

Porto Alegre, , Brazil

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Research Site 609

Vitória, , Brazil

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Research Site 155

Blagoevgrad, , Bulgaria

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Research Site 156

Dupnitsa, , Bulgaria

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Research Site 157

Pleven, , Bulgaria

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Research Site 801

Pleven, , Bulgaria

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Research Site 804

Pleven, , Bulgaria

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Plovdiv, , Bulgaria

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Research Site 151

Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Sofia, , Bulgaria

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Veliko Tarnovo, , Bulgaria

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Research Site 106

Burnaby, , Canada

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London, , Canada

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Montreal, , Canada

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Ottawa, , Canada

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Research Site 455

Bordeaux, , France

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Brest, , France

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Reserach Site 451

Clermont-Ferrand, , France

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Limoges, , France

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Nîmes, , France

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Paris, , France

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Pringy, , France

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Strasbourg, , France

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Tours, , France

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Augsburg, , Germany

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Berlin, , Germany

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Berlin, , Germany

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Bonn, , Germany

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Cologne, , Germany

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Dresden, , Germany

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Hamburg, , Germany

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Heidelberg, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Minden, , Germany

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Regensburg, , Germany

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Rostock, , Germany

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Tübingen, , Germany

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Athens, , Greece

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Heraklion, , Greece

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Ioannina, , Greece

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Larissa, , Greece

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Marousi, , Greece

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Pátrai, , Greece

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Pátrai, , Greece

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Thessaloniki, , Greece

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Ahmedabad, , India

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Bangalore, , India

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Mangalore, , India

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New Delhi, , India

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Bari, , Italy

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Catania, , Italy

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Cefalù, , Italy

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Florence, , Italy

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Milan, , Italy

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Napoli, , Italy

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Napoli, , Italy

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Orbassano, , Italy

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Palermo, , Italy

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Pozzilli, , Italy

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Roma, , Italy

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Roma, , Italy

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Riga, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Kaunas, , Lithuania

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Klaipėda, , Lithuania

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Šiauliai, , Lithuania

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Vilnius, , Lithuania

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Kuala Lumpur, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuala Lumpur, , Malaysia

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Kuching, , Malaysia

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Seberang Jaya, , Malaysia

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Chisinau, , Moldova

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Chisinau, , Moldova

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Bergen, , Norway

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Drammen, , Norway

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Namsos, , Norway

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Baguio City, , Philippines

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Cebu City, , Philippines

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Reserach Site 267

Bydgoszcz, , Poland

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Bydgoszcz, , Poland

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Katowice, , Poland

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Research site 846

Katowice, , Poland

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Katowice-Ochojec, , Poland

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Krakow, , Poland

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Lodz, , Poland

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Lodz, , Poland

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Nowa Sól, , Poland

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Poznan, , Poland

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Rzeszów, , Poland

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Siemianowice Śląskie, , Poland

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Szczecin, , Poland

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Warsaw, , Poland

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Warsaw, , Poland

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Reserach Site 275

Warsaw, , Poland

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Research Site 269

Wroclaw, , Poland

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Zabrze, , Poland

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Zamość, , Poland

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Aveiro, , Portugal

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Braga, , Portugal

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Coimbra, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Lisbon, , Portugal

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Research SIte 284

Matosinhos Municipality, , Portugal

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Porto, , Portugal

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Pragal, , Portugal

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Santa Maria da Feira, , Portugal

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Torres Vedras, , Portugal

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Guaynabo, , Puerto Rico

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Brasov, , Romania

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Bucharest, , Romania

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Caracal, , Romania

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Târgu Mureş, , Romania

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Kazan', , Russia

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Kazan', , Russia

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Kemerovo, , Russia

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Kirov, , Russia

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Krasnodar, , Russia

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Krasnoyarsk, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Nizhny Novgorod, , Russia

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Novosibirsk, , Russia

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Novosibirsk, , Russia

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Novosibirsk, , Russia

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Novosibirsk, , Russia

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Rostov-on-Don, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Research Site 326

Saransk, , Russia

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Research Site 321

Sestroretsk, , Russia

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Tyumen, , Russia

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Research Site 493

Riyadh, , Saudi Arabia

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Research Site 571

Singapore, , Singapore

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Research site 572

Singapore, , Singapore

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Research Site 351

Banská Bystrica, , Slovakia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Bratislava, , Slovakia

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Dubnica nad Váhom, , Slovakia

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Trenčín, , Slovakia

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Trnava, , Slovakia

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Celje, , Slovenia

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Ljubljana, , Slovenia

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Maribor, , Slovenia

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Cape Town, , South Africa

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Cape Town, , South Africa

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Cape Town, , South Africa

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Pretoria, , South Africa

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Alcorcón, , Spain

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Barakaldo, , Spain

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Barcelona, , Spain

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Córdoba, , Spain

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El Palmar, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Málaga, , Spain

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Seville, , Spain

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Research Site 385

Valencia, , Spain

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Valencia, , Spain

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Vigo, , Spain

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Research Site 512

Gothenburg, , Sweden

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Malmo, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Aarau, , Switzerland

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Bern, , Switzerland

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Lugano, , Switzerland

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Research Site 583

Bangkoknoi, , Thailand

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Research Site 582

Muang, , Thailand

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Ankara, , Turkey (Türkiye)

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Research Site 539

Izmir, , Turkey (Türkiye)

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Research Site 533

Kocaeli, , Turkey (Türkiye)

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Konya, , Turkey (Türkiye)

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Research Site 540

Mersin, , Turkey (Türkiye)

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Research Site 535

Samsun, , Turkey (Türkiye)

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Trabzon, , Turkey (Türkiye)

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Chernihiv, , Ukraine

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Chernihiv, , Ukraine

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Dnipro, , Ukraine

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Dnipro, , Ukraine

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Dnipro, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kharkiv, , Ukraine

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Kherson, , Ukraine

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Kyiv, , Ukraine

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Kyiv, , Ukraine

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Lutsk, , Ukraine

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Lviv, , Ukraine

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Poltava, , Ukraine

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Rivne, , Ukraine

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Ternopil, , Ukraine

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Uzhhorod, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhzhia, , Ukraine

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Zaporizhzhia, , Ukraine

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Research Site 631

Zaporizhzhia, , Ukraine

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Research Site 626

Zhytomyr, , Ukraine

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Countries

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United States Belarus Brazil Bulgaria Canada France Germany Greece India Italy Latvia Lithuania Malaysia Moldova Norway Philippines Poland Portugal Puerto Rico Romania Russia Saudi Arabia Singapore Slovakia Slovenia South Africa Spain Sweden Switzerland Thailand Turkey (Türkiye) Ukraine

References

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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.

Reference Type RESULT
PMID: 39307151 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2019-004980-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200527_0082

Identifier Type: -

Identifier Source: org_study_id

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