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

NCT04586023 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: GN422722020-001168-282022-502618-95-00
• Study Type: interventional
• Target: 751
• Locations: 17 countries
• Sites: 108

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 in a 1:1 ratio to receive either fenebrutinib or teriflunomide. At the end of the double-blind treatment (DBT) phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension (OLE) 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 (PO) fenebrutinib, with teriflunomide-matching placebo.

Drug: Fenebrutinib; Drug: Placebo

Teriflunomide

ACTIVE COMPARATOR

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

Drug: Teriflunomide; Drug: Placebo

Interventions

Placebo DRUG

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

Fenebrutinib; Teriflunomide

Fenebrutinib DRUG

Participants will receive fenebrutinib.

Fenebrutinib

Teriflunomide DRUG

Participants will receive teriflunomide.

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 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 multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
• Any known or suspected active infection at screening, including but not limited to a positive screening tests for hepatitis B (HBV) and hepatitis C (HCV), 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 (GI) 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 (108)

North Central Neurology Associates

Cullman, Alabama, 35058, United States

Location

Xenoscience

Phoenix, Arizona, 85004, United States

Location

Los Angeles Biomedical Research Institute at Harbor-UCLA

Torrance, California, 90502, United States

Location

KI Health Partners, LLC

Stamford, Connecticut, 06905, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

American Health Network Institute, LLC

Avon, Indiana, 46123, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Neuro Institute of New England P.C.

Foxborough, Massachusetts, 02035, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Hope Neurology

Knoxville, Tennessee, 37922, United States

Location

Integrated Neurology Services PLLC

Falls Church, Virginia, 22043, United States

Location

Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, 53226-3596, United States

Location

Kepler Universitätskliniken GmbH - Med Campus III

Linz, 4021, Austria

Location

L2 Ip Instituto de Pesquisas Clinicas Ltda ME

Brasília, Federal District, 70200-730, Brazil

Location

Santa Casa de Misericordia

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Instituto de Neurologia de Curitiba

Curitiba, Paraná, 81210-310, Brazil

Location

IMV Pesquisa Neurológica

Porto Alegre, Rio Grande do Sul, 90110-000, Brazil

Location

Núcleo de Pesquisa do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, 90430-001, Brazil

Location

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Clinica Neurologica

Joinville, Santa Catarina, 89202-190, Brazil

Location

Praxis Pesquisa Médica

Santo André, São Paulo, 09090-790, Brazil

Location

CEMEC - Centro Multidisciplinar de Estudos Clínicos

São Bernardo do Campo, São Paulo, 09715-090, Brazil

Location

Centro de Pesquisas Clinicas

São Paulo, São Paulo, 01228-200, Brazil

Location

Hospital Santa Marcelina

São Paulo, São Paulo, 08270-070, Brazil

Location

Jordy Sinapse Medicina LTDA ME

São Paulo, Brazil

Location

UMHAT Dr. Georgi Stranski

Pleven, 5800, Bulgaria

Location

MHATNP Sveti Naum EAD

Sofia, 1113, Bulgaria

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1Z1, Canada

Location

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital

Chicoutimi, Quebec, G7H 5H6, Canada

Location

MUCH - Montreal Neurological Institute & Hospital

Montreal, Quebec, H3A 2B4, Canada

Location

CHU de Québec

Québec, Quebec, G1J 1Z4, Canada

Location

Sydvestjysk Sygehus Esbjerg

Esbjerg, 6700, Denmark

Location

Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken

Sønderborg, 6400, Denmark

Location

Hopital Gabriel Montpied CHU de Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Hôpital Pasteur

Nice, 06002, France

Location

Hôpital Charles Nicolle

Rouen, 76031, France

Location

CHU toulouse - Hôpital Purpan

Toulouse, 31059, France

Location

Hospital Eginition

Athens, 115 28, Greece

Location

University General Hospital of Larisa

Larissa, 411 10, Greece

Location

AHEPA Univ. General Hospital of Thessaloniki

Thessaloniki, 54636, Greece

Location

Nucare

Guatemala City, 01015, Guatemala

Location

Zydus Hospital

Ahmedabad, Gujarat, 380054, India

Location

Seth G.S Medical College K.E.M Hospital

Mumbai, Maharashtra, 400012, India

Location

Deenanath Mangeshkar Hospital & Research Centre

Pune, Maharashtra, 411004, India

Location

Sahyadri Superspeciality Hospital

Pune, Maharashtra, 411006, India

Location

Max Super Speciality Hospital

New Delhi, National Capital Territory of Delhi, 110017, India

Location

Sir Gangaram Hospital

New Delhi, National Capital Territory of Delhi, 110060, India

Location

Christian Medical College and Hospital

Ludhiana, Punjab, 141008, India

Location

SRM Institute of Medical Sciences

Vadapalani, Tamil Nadu, 600026, India

Location

Postgraduate Institute of Medical Education and Research

Chandigarh, 160012, India

Location

Universita? G. D'Annunzio

Chieti, Abruzzo, 66100, Italy

Location

Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari

Bari, Apulia, 70124, Italy

Location

A. O. U. Federico II

Naples, Campania, 80131, Italy

Location

Ospedale S.Camillo Forlanini

Rome, Lazio, 00152, Italy

Location

Policlinico Universitario A. Gemelli

Rome, Lazio, 00168, Italy

Location

NCL Institute Neuroscience

Rome, Lazio, 00178, Italy

Location

Irccs A.O.U.San Martino Ist

Genoa, Liguria, 16132, Italy

Location

Fond. Istituto Neurologico C.Besta

Milan, Lombardy, 20133, Italy

Location

Ospedale Civile di Montichiari

Montichiari, Lombardy, 25018, Italy

Location

IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla

Pavia, Lombardy, 27100, Italy

Location

IRCCS Istituto Neurologico Neuromed

Pozzilli, Molise, 86077, Italy

Location

Ospedale Binaghi

Cagliari, Sardinia, 09126, Italy

Location

AOU Policlinico Giaccone

Palermo, Sicily, 90129, Italy

Location

Mexico Centre for Clinical Research

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

Location

Clinstile S.A de C.V.

Mexico City, Mexico CITY (federal District), 06700, Mexico

Location

Grupo Médico Camino S.C.

México, Mexico CITY (federal District), 03600, Mexico

Location

Unidad de Investigación en Salud

Chihuahua City, 31203, Mexico

Location

Unidad de investigacion en salud (UIS)

Mexico City, 14050, Mexico

Location

NZOZ Vitamed

Bydgoszcz, 85-079, Poland

Location

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, 85-796, Poland

Location

COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika

Gdansk, 80-803, Poland

Location

RESMEDICA Spolka z o.o.

Kielce, 25-726, Poland

Location

Centrum Neurologii Klinicznej

Krakow, 31-505, Poland

Location

Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.

Krakow, 31-637, Poland

Location

Centrum Neurologii Krzysztof Selmaj

Lodz, 90-324, Poland

Location

Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.

Oświęcim, 32-600, Poland

Location

Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych

Plewiska, 62-064, Poland

Location

MedPolonia

Poznan, 60-693, Poland

Location

NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek

Późna, 61-853, Poland

Location

Wojewódzki Szpital Specjalistyczny Nr 3

Rybnik, 44-200, Poland

Location

Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie

Warsaw, 02-097, Poland

Location

Wro Medica

Wroc?aw, 51-685, Poland

Location

IBISMED Wielospecjalistyczne Centrum Medyczne

Zabrze, 41-800, Poland

Location

Krasnoyarsk State Medical Academy

Krasnoyarsk, Krasnoyarsk Krai, 660022, Russia

Location

FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

Krasnoyarsk, Krasnoyarsk Krai, 660037, Russia

Location

Federal center of brain research and neurotechnologies

Moskva, Moscow Oblast, 117997, Russia

Location

Regional Clinical Hospital N.A. Semashko

Nizhny Novgorod, Niznij Novgorod, 603126, Russia

Location

National Center of Social Significant Disease

Saint Petersburg, Sankt-Peterburg, 197110, Russia

Location

Regional clinical hospital named after prof. S.V. Ochapovsky

Krasnodar, 350086, Russia

Location

Nebbiolo Center for Clinical Trials

Tomsk, 634009, Russia

Location

Keimyung University Dongsan Medical Center

Daegu, 41931, South Korea

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Gazi University Medical Faculty

Ankara, 06500, Turkey (Türkiye)

Location

Baskent Universitesi Ankara Hastanesi

Çankaya, 06490, Turkey (Türkiye)

Location

Bakirkoy State Mental Hospital

Istanbul, 34000, Turkey (Türkiye)

Location

Sancaktepe Training and Research Hospital

Istanbul, 34785, Turkey (Türkiye)

Location

Selcuk University Medical Faculty

Istanbul, 42131, Turkey (Türkiye)

Location

Kocaeli University Hospital

Kocaeli, 41380, Turkey (Türkiye)

Location

Ege Üniversitesi Tip Fakültesi

Lzmir, 35100, Turkey (Türkiye)

Location

Mersin University Medical Faculty

Mersin, 33079, Turkey (Türkiye)

Location

Ondokuz Mayis University School of Medicine

Samsun, 55139, Turkey (Türkiye)

Location

Karadeniz Tecnical Uni. Med. Fac.

Trabzon, 61080, Turkey (Türkiye)

Location

Van Yuzuncu Yil University Hospital

Van, 65080, Turkey (Türkiye)

Location

Salford Royal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

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 24, 2021
• Primary Completion: September 5, 2025
• Study Completion (Estimated): July 9, 2027
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

GB (1); GU (1); ME (5); IN (9); IT (13); KR (4); FR (4); CA (5); BR (12); GR (3); TU (11); BU (2); US (13); PL (15); AU (1); RU (7); DK (2)