A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)

NCT04586010 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: GN418512019-004857-102022-502609-14-00
• Study Type: interventional
• Target: 746
• Locations: 23 countries
• Sites: 160

Brief Summary

A study to evaluate the efficacy and safety of fenebrutinib on disability progression and relapse rate in adult participants with RMS. Eligible participants will be randomized 1:1 to either fenebrutinib or teriflunomide. At the end of the DBT phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension phase of the study.

Conditions

Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Annualized Relapse Rate (ARR)

  Minimum of 96 weeks

Secondary Outcomes (12)

• Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)

  Minimum of 96 weeks

• Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24)

  Minimum of 96 weeks

• Time to Onset of 12-week Confirmed Disability Progression (CDP12)

  Minimum of 96 weeks

• Time to Onset of 24-week Confirmed Disability Progression (CDP24)

  Minimum of 96 weeks

• Total Number of T1 Gadolinium Enhancing (Gd+) Lesions, New and/or Enlarging T2-weighted Lesions as Detected by Magnetic Resonance Imaging (MRI)

  Baseline, Weeks 12, 24, 48 and 96

Study Arms (2)

Fenebrutinib

EXPERIMENTAL

Participants will receive oral fenebrutinib with teriflunomide-matching placebo.

Drug: Fenebrutinib; Drug: Placebo

Teriflunomide

ACTIVE COMPARATOR

Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion.

Drug: Teriflunomide; Drug: Placebo

Interventions

Fenebrutinib DRUG

Participants will receive fenebrutinib.

Fenebrutinib

Teriflunomide DRUG

Participants will receive teriflunomide.

Teriflunomide

Placebo DRUG

Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.

Fenebrutinib; Teriflunomide

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening.
• A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria.
• Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in \< 240 seconds.
• Ability to perform the Timed 25-Foot Walk Test (T25FWT) in \<150 seconds.
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.
• Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib.
• Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the accelerated teriflunomide elimination procedure (ATEP) prior to the first administration of open-label fenebrutinib.
• For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs.
• For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm.

You may not qualify if:

• Disease duration of \> 10 years from the onset of symptoms and an EDSS score at screening \< 2.0.
• Female participants who are pregnant or breastfeeding, or intending to become pregnant.
• Male participants who intend to father a child during the study.
• A diagnosis of primary progressive MS (PPMS) or non-active secondary progressive MS (SPMS).
• Any known or suspected active infection at screening, including but not limited to a positive screening test for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML).
• History of cancer including hematologic malignancy and solid tumors within 10 years of screening.
• Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study and clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
• Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption.
• Hypoproteinemia.
• Acute liver disease
• Chronic liver disease unless considered stable for \> 6 months.
• Presence of cirrhosis (Child-Pugh Class A, B, or C) or Gilbert's Syndrome.
• Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia.
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study.
• History of alcohol or other drug abuse within 12 months prior to screening.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (160)

University of Alabama Birmingham

Birmingham, Alabama, 35233, United States

Location

Alabama Neurology Associates

Homewood, Alabama, 35209, United States

Location

Center for Neurology and Spine - Phoenix - Hunt - PPDS

Phoenix, Arizona, 85032, United States

Location

Profound Research, LLC

Carlsbad, California, 92011, United States

Location

University of California Irvine

Irvine, California, 92697, United States

Location

SC3 Research Group, Inc

Pasadena, California, 91105, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

Mountain View Clinical Research

Denver, Colorado, 80209, United States

Location

Advanced Neurology of Colorado, LLC

Fort Collins, Colorado, 80528, United States

Location

Neurology Associates, PA; Research Department

Maitland, Florida, 32751, United States

Location

NorthShore University HealthSystem

Highland Park, Illinois, 60035, United States

Location

Fort Wayne Neurological Center

Fort Wayne, Indiana, 46805, United States

Location

The NeuroMedical Center

Baton Rouge, Louisiana, 70810, United States

Location

Ochsner LSU Health

Shreveport, Louisiana, 71103, United States

Location

Johns Hopkins University School Of Medicine; Outpatient Center

Baltimore, Maryland, 21287, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Holy Name Hospital; Institute For Clinical Research

Teaneck, New Jersey, 07666, United States

Location

University of New Mexico; MS Specialty Clinic

Albuquerque, New Mexico, 87131, United States

Location

Miami Valley Hospital South; Dayton Physician's Office

Centerville, Ohio, 45459, United States

Location

OhioHealth

Columbus, Ohio, 43214, United States

Location

The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company

Columbus, Ohio, 43235, United States

Location

Oklahoma Medical Research Foundation; MS Center of Excellence

Oklahoma City, Oklahoma, 73104, United States

Location

St. Luke's University Health network

Bethlehem, Pennsylvania, 18015, United States

Location

Premier Neurology

Greenville, South Carolina, 29605, United States

Location

New Orleans Center for Clinical Research

Knoxville, Tennessee, 37920, United States

Location

North Texas Institute of Neurology and Headache NextStage Clinical Research Clinic

Plano, Texas, 75024, United States

Location

Texas Institute for Neurological Disorders

Sherman, Texas, 75092, United States

Location

Multiple Sclerosis Center of Greater Washington

Vienna, Virginia, 22182, United States

Location

Evergreen MS Center

Kirkland, Washington, 98034, United States

Location

Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders

Milwaukee, Wisconsin, 53215, United States

Location

Instituto de Investigaciones Metabolicas (Idim)

Buenos Aires, C1012AAR, Argentina

Location

IME - Instituto Médico Especializado

Buenos Aires, C1405BCH, Argentina

Location

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

Buenos Aires, C1424, Argentina

Location

CIER

C. A. B. A., C1055AAF, Argentina

Location

Diagnostico Medico Oroño

Rosario, 2000, Argentina

Location

Cer San Juan

San Juan, J5400CEP, Argentina

Location

Centro de Investigaciones Médicas Tucuman

San Miguel de Tucumán, T4000AXL, Argentina

Location

Peking University First Hospital

Beijing, 100034, China

Location

Beijing Tiantan Hospital,Capital Medical University

Beijing, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Xiangya Hospital Central South University

Changsha, 410008, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

The First Affiliated Hospital, Chongqing Medical University

Chongqing, 400016, China

Location

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, 510080, China

Location

The second Affiliated Hospital of Guangzhou Medical University

Guangzhou, 510260, China

Location

The affiliated Hospital of Guiyang Medical College

Guiyang, China

Location

The First People?s Hospital of Yunnan Province

Kunming, 650021, China

Location

The Second Hospital of Hebei Medical University

Shijiazhuang, 05000, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, 215031, China

Location

1st Affiliated Hospital of Shanxi Medical University

Taiyuan, China

Location

Tianjin Medical University General Hospital

Tianjin, 300052, China

Location

Xinjiang People Hospital

Ürümqi, 830000, China

Location

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430030, China

Location

Tangdu Hospital, The Fourth Military Medical University

Xi'an, China

Location

NeuroINC

Santiago de los Caballeros, 51000, Dominican Republic

Location

Hospital Padre Billini

Santo Domingo, 10210, Dominican Republic

Location

Helsinki University Central Hospital

Helsinki, 00290, Finland

Location

New Hospitals

Tbilisi, 0114, Georgia

Location

Pineo Medical Ecosystem

Tbilisi, 0114, Georgia

Location

St. Michael hospital

Tbilisi, 0159, Georgia

Location

MediClab Georgia

Tbilisi, 0160, Georgia

Location

Khechinashvili University Hospital

Tbilisi, 0179, Georgia

Location

Jüdisches Krankenhaus Berlin

Berlin, 13347, Germany

Location

Studienzentrum Dr. Bischof GmbH

Böblingen, 71034, Germany

Location

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

Dresden, 01307, Germany

Location

Universitätsklinikum Gießen und Marburg GmbH

Giessen, 35385, Germany

Location

Uniklinik Schleswig-Holstein

Kiel, 24105, Germany

Location

Praxis Dr. med. Andreas Kowalik, Arzt für Neurologie und Psychiatrie

Stuttgart, 70174, Germany

Location

Universitätsklinikum Tübingen, Zentrum für Neurologie

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz

Westerstede, 26655, Germany

Location

Pamela Youde Nethersole Eastern Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

Clinexpert Kft.

Budapest, 1033, Hungary

Location

S-Medicon Egeszsegugyi Szolgaltato Kft.

Budapest, 1044, Hungary

Location

Markhot Ferenc Oktatokorhaz és Rendelointezet

Eger, 3300, Hungary

Location

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, 2143, Hungary

Location

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

Szeged, 6725, Hungary

Location

AO.U. Policlinico Riuniti Foggia

Foggia, Apulia, 71100, Italy

Location

AOU Seconda Università degli Studi

Naples, Campania, 80131, Italy

Location

AOU Policlinico - Università L. Vanvitelli

Naples, Campania, 80138, Italy

Location

A.O.U. di Parma

Parma, Emilia-Romagna, 43126, Italy

Location

Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla

Rome, Lazio, 00133, Italy

Location

Policlinico Umberto I

Rome, Lazio, 00185, Italy

Location

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, 00189, Italy

Location

ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla

Bergamo, Lombardy, 24127, Italy

Location

IRCCS Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Ospedale Regina Montis Regalis

Mondovì (CN), Piedmont, 12084, Italy

Location

AOU Policlinico V. Emanuele - P.O G. Rodolico

Catania, Sicily, 95123, Italy

Location

Azienda Ospedaliera di Padova

Padua, Veneto, 35128, Italy

Location

The Aga Khan University-Kenya.

Nairobi, 00100, Kenya

Location

Clinical Research Institute Saltillo

Saltillo, Coahuila, 25050, Mexico

Location

Grupo Medico de Investigacion Clinica Multidisciplinaria

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

Health Pharma Professional Research

Mexico City, Mexico CITY (federal District), 03100, Mexico

Location

Neurociencias Estudios Clinicos S.C.

Culiacán, Sinaloa, 80020, Mexico

Location

Hospital General de Mexico

Mexico, Tlaxcala, 06726, Mexico

Location

Zuyderland Medisch Centrum - Sittard Geleen

Sittard-Geleen, 6162 BG, Netherlands

Location

Clinical Hospital Stip

Shtip, 2000, North Macedonia

Location

PHO General City Hospital 8th September Center for dialysis

Skopje, 1000, North Macedonia

Location

University Clinic for Neurology - Skopje

Skopje, 1000, North Macedonia

Location

Hospital IV Alberto Sabogal Sologuren

Bellavista, Callao 2, Peru

Location

Hospital Nacional Guillermo Almenara Irigoyen

La Victoria, Lima, Lima 13, Peru

Location

Hospital Nacional Dos de Mayo

Lima, 15018, Peru

Location

Clinica Internacional Sede Lima

Lima, Lima 01, Peru

Location

Hospital Maria Auxiliadora

Lima, Lima 29, Peru

Location

Clinica Centenario Peruano Japonesa

Pueblo Libre, Lima 21, Peru

Location

ProNeuro Centrum Medyczne

?ory, 44-240, Poland

Location

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, 85-796, Poland

Location

Care Clinic

Katowice, 40-568, Poland

Location

MT Medic Krosno

Krosno, 38-400, Poland

Location

Centrum Neurologii Krzysztof Selmaj

Lodz, 90-324, Poland

Location

Rodzinne Centrum Medyczne Lubimed.pl

Lublin, 20-492, Poland

Location

Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych

Plewiska, 62-064, Poland

Location

MedPolonia

Poznan, 60-693, Poland

Location

Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

Warsaw, 02-957, Poland

Location

IBISMED Wielospecjalistyczne Centrum Medyczne

Zabrze, 41-800, Poland

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

HUC

Coimbra, 3000-075, Portugal

Location

Hospital Santo Antonio dos Capuchos

Lisbon, 1169-050, Portugal

Location

Hospital da Luz

Lisbon, 1500-650, Portugal

Location

Hospital Geral de Santo Antonio

Porto, 4099-001, Portugal

Location

Hospital de Sao Joao

Porto, 4200-319, Portugal

Location

Centro Hospitalar Entre o Douro e Vouga E.P.E. - Hospital de São Sebastião

Santa Maria da Feira, 4520-211, Portugal

Location

Republican clinical hospital named after G.G. Kuvatov

Ufa, Bashkortostan Republic, 450005, Russia

Location

Leningrad Regional Clinical Hospital

Saint Petersburg, Sankt-Peterburg, 194291, Russia

Location

Pavlov State Medical Uni

Saint Petersburg, Sankt-Peterburg, 197022, Russia

Location

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, Ulyanovsk Oblast, 432063, Russia

Location

Center of Cardiology and Neurology

Kirov, 610007, Russia

Location

FSBIH Siberian Regional Medical Centre of FMBA of Russia

Novosibirsk, 630007, Russia

Location

University Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Hospital Universitari de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Quiron de Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario Virgen de Arrixaca

EL Palmar (EL Palmar), Murcia, 30120, Spain

Location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, 36213, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario de la Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Regional Universitario de Malaga ? Hospital General

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Inselspital Bern Medizin Neurologie

Bern, 3010, Switzerland

Location

Ospedale Regionale di Lugano - Civico

Lugano, 6903, Switzerland

Location

Hopital Razi

Mannouba, 2010, Tunisia

Location

Fattouma Bourguiba Hospital

Monastir, 5000, Tunisia

Location

Hospital Habib Bourguiba

Sfax, 3029, Tunisia

Location

Salutem Medical Center

Vinnytsia, KIEV Governorate, 21009, Ukraine

Location

Separated structural unit ?University hospital? of Dnipro State Medical University

Dnipro, Tavria Okruha, Ukraine

Location

SI USSRI of Medical and Social Problems of Disabilities of MOHU

Dnipro, 49027, Ukraine

Location

Ams of Ukraine

Kharkiv, 61068, Ukraine

Location

Medical Center Dopomoga Plus

Kyiv, 02123, Ukraine

Location

Medical Center of Private Execution First Private Clinic

Kyiv, 03037, Ukraine

Location

Lviv Regional Clinical Hospital

Lviv, 79010, Ukraine

Location

"Neurofocus" LLC

Lviv, 79029, Ukraine

Location

Odesa Regional Clinical Hospital

Odesa, 65117, Ukraine

Location

Medical Clinical Research Center of Medical Center LLC Health Clinic

Vinnytsi, 21009, Ukraine

Location

LCC "Medical center "Unimed"

Zaporizhzhia, 69035, Ukraine

Location

Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council

Zaporizhzhia, 69600, Ukraine

Location

MeSH Terms

Interventions

fenebrutinib; teriflunomide

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor will also be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2020
• First Posted: October 14, 2020
• Study Start: March 17, 2021
• Primary Completion: January 27, 2026
• Study Completion (Estimated): November 30, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

FI (1); RU (6); PE (6); PL (10); ES (11); KE (1); AR (7); US (32); CN (17); IT (12); NL (1); GE (5); DO (2); PT (7); SE (1); DE (9); ME (5); NO (3); CH (2); TU (3); UA (12); HK (2); HU (5)