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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04586023
Other study ID # GN42272
Secondary ID 2020-001168-2820
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date March 24, 2021
Est. completion date November 27, 2025

Study information

Verified date April 2024
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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. Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis of the study.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 751
Est. completion date November 27, 2025
Est. primary completion date October 2, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria: - 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. Exclusion Criteria: - 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 tests 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. - 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. - History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of human immunodeficiency virus (HIV) infection. - Inability to complete an MRI scan. - Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed). - Receipt of a live-attenuated vaccine within 6 weeks prior to randomization. - Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period. OLE Inclusion Criteria: - 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.

Study Design


Intervention

Drug:
Fenebrutinib
Participants will receive fenebrutinib.
Teriflunomide
Participants will receive teriflunomide.
Placebo
Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.

Locations

Country Name City State
Austria Kepler Universitätskliniken GmbH - Med Campus III; Neurologie & Psychiatrie Linz
Austria Medizinische Universität Wien; Univ.Klinik fuer Neurologie Wien
Brazil Santa Casa de Misericordia; de Belo Horizonte Belo Horizonte MG
Brazil L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar Brasilia DF
Brazil Instituto de Neurologia de Curitiba Curitiba PR
Brazil Clinica Neurologica; Neurocirurgica de Joinville Joinville SC
Brazil Hospital Sao Lucas - PUCRS Porto Alegre RS
Brazil IMV Pesquisa Neurológica Porto Alegre RS
Brazil Núcleo de Pesquisa do Rio Grande do Sul Porto Alegre RS
Brazil Praxis Pesquisa Médica Santo Andre SP
Brazil CEMEC - Centro Multidisciplinar de Estudos Clínicos Sao Bernardo Do Campo SP
Brazil Centro de Pesquisas Clinicas; CPCLIN Sao Paulo SP
Brazil Hospital Santa Marcelina; AME - Ambulatório de Especialidades Médicas Sao Paulo SP
Brazil Jordy Sinapse Medicina LTDA ME Sao Paulo SP
Bulgaria UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases Pleven
Bulgaria MHATNP Sveti Naum EAD Sofia
Canada CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital Chicoutimi Quebec
Canada University of Alberta Hospital Edmonton Alberta
Canada Recherche Sepmus Inc. Greenfield Park Quebec
Canada MUCH - Montreal Neurological Institute & Hospital Montreal Quebec
Canada The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis Ottawa Ontario
Canada CHU de Québec Quebec City Quebec
Denmark Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken Aabenraa
Denmark Sydvestjysk Sygehus Esbjerg; Neurologisk Afd., Skleroseklinikken Esbjerg
France Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B Clermont-Ferrand
France Hôpital Pasteur; Service de Neurologie Nice
France Hôpital Charles Nicolle; Service de Neurologie Rouen
France CHU toulouse - Hôpital Purpan; Departement de Neurologie Toulouse
Greece University General Hospital of Ioannina; Neurology Clinic ??a????a
Greece Hospital Eginition; First Department of Neurology Athens
Greece University General Hospital of Larisa; Neurology Clinic Larisa
Greece AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept. Thessaloniki
Guatemala Nucare Ciudad Guatemala
India Zydus Hospital; Department of Neuro Sciences Ahmadabad CITY Gujarat
India Postgraduate Institute of Medical Education and Research Chandigarh
India Christian Medical College and Hospital Ludhiana Punjab
India Seth G.S Medical College K.E.M Hospital Mumbai Maharashtra
India Max Super Speciality Hospital New Delhi Delhi
India Sir Gangaram Hospital NEW Delhi Delhi Delhi
India Deenanath Mangeshkar Hospital & Research Centre Pune Maharashtra
India Sahyadri Superspeciality Hospital Pune City Maharashtra
India SRM Institute of Medical Sciences Vadapalani Tamil NADU
Italy Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari; Neuroscienze e Organi di Senso Bari Puglia
Italy Ospedale Binaghi; Centro Sclerosi Multipla Cagliari Sardegna
Italy Universita? G. D'Annunzio; Dipartimento di Neuroscienze, Imaging e Scienze Cliniche Chieti Abruzzo
Italy Irccs A.O.U.San Martino Ist; Dinogmi Genova Liguria
Italy Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari Milano Lombardia
Italy Ospedale Civile di Montichiari; Centro Sclerosi Multipla Montichiari Lombardia
Italy A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche Napoli Campania
Italy AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla Palermo Sicilia
Italy IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla Pavia Lombardia
Italy IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla Pozzilli Molise
Italy NCL Institute Neuroscience Roma Lazio
Italy Ospedale S.Camillo Forlanini; UOSD Day Hospital Neurologico e Neurochirurgico Roma Lazio
Italy Policlinico Universitario A. Gemelli; UOC Neurologia - Centro Sclerosi Multipla Roma Lazio
Korea, Republic of Keimyung University Dongsan Medical Center Daegu
Korea, Republic of National Cancer Center Goyang-si
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Mexico Unidad de Investigación en Salud; Psiquiatria Chihuahua
Mexico Grupo Médico Camino S.C. Ciudad de México Mexico CITY (federal District)
Mexico Mexico Centre for Clinical Research Ciudad de México Mexico CITY (federal District)
Mexico Unidad de investigacion en salud (UIS); Neurociencias Ciudad de México
Mexico Clinstile S.A de C.V. Mexico City Mexico CITY (federal District)
Poland Neurocentrum Bydgoszcz sp. z o.o Bydgoszcz
Poland NZOZ Vitamed Bydgoszcz
Poland COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny Gdansk
Poland RESMEDICA Spolka z o.o. Kielce
Poland Centrum Neurologii Klinicznej Krakow
Poland Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o. Krakow
Poland Centrum Neurologii Krzysztof Selmaj Lodz
Poland Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k. Oswiecim
Poland Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych Plewiska
Poland NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek Pozna?
Poland MedPolonia Poznan
Poland Wojewódzki Szpital Specjalistyczny Nr 3 Rybnik
Poland Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie Warszawa
Poland Wro Medica Wroc?aw
Poland IBISMED Wielospecjalistyczne Centrum Medyczne Zabrze
Russian Federation Regional clinical hospital named after prof. S.V. Ochapovsky Krasnodar
Russian Federation FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency Krasnoyarsk Krasnojarsk
Russian Federation Krasnoyarsk State Medical Academy Krasnoyarsk Krasnojarsk
Russian Federation Federal center of brain research and neurotechnologies Moskva Moskovskaja Oblast
Russian Federation Regional Clinical Hospital N.A. Semashko; Neurology Nizhny Novgorod Niznij Novgorod
Russian Federation State Novosibirsk Regional Clinical Hospital Novosibirsk
Russian Federation National Center of Social Significant Disease Sankt-peterburg Leningrad
Russian Federation Nebbiolo Center for Clinical Trials Tomsk
Turkey Gazi University Medical Faculty; Departmant of Norology Ankara
Turkey Hacettepe University Medical Faculty; Neurology Ankara
Turkey Baskent Universitesi Ankara Hastanesi; Noroloji Bolumu Çankaya
Turkey Bakirkoy State Mental Hospital Istanbul
Turkey Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali Istanbul
Turkey Sancaktepe Training and Research Hospital; Neurology Istanbul
Turkey Selcuk University Medical Faculty; Norology department Istanbul
Turkey Kocaeli University Hospital; Department of Neurology Kocaeli
Turkey Ege Üniversitesi Tip Fakültesi Lzmir
Turkey Mersin University Medical Faculty; Neurology Mersin
Turkey Ondokuz Mayis University School of Medicine; Neurology Samsun
Turkey Karadeniz Tecnical Uni. Med. Fac.; Neurology Trabzon
Turkey Van Yuzuncu Yil University Hospital; Neurology Van
United Kingdom Salford Royal NHS Foundation Trust Salford
United Kingdom Recognition Health Winchester
United States American Health Network Institute, LLC Avon Indiana
United States University of Cincinnati; Department of Neurology Cincinnati Ohio
United States North Central Neurology Associates Cullman Alabama
United States Wayne State University; Department of Neurology Detroit Michigan
United States Integrated Neurology Services PLLC Falls Church Virginia
United States Neuro Institute of New England P.C.; Research Foxboro Massachusetts
United States University of Kansas Medical Center Kansas City Kansas
United States Hope Neurology Knoxville Tennessee
United States Medical College of Wisconsin, Inc. Milwaukee Wisconsin
United States Xenoscience Phoenix Arizona
United States KI Health Partners, LLC; New England Institute for Clinical Research Stamford Connecticut
United States Stanford University Medical Center; Stanford Neuroscience Health Center Stanford California
United States University of South Florida Tampa Florida
United States Los Angeles Biomedical Research Institute at Harbor-UCLA Torrance California
United States Georgetown University Medical Center Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Austria,  Brazil,  Bulgaria,  Canada,  Denmark,  France,  Greece,  Guatemala,  India,  Italy,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Annualized Relapse Rate (ARR) Minimum of 96 weeks
Secondary Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12) Minimum of 96 weeks
Secondary Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24) Minimum of 96 weeks
Secondary Time to Onset of 12-week Confirmed Disability Progression (CDP12) Minimum of 96 weeks
Secondary Time to Onset of 24-week Confirmed Disability Progression (CDP24) Minimum of 96 weeks
Secondary 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
Secondary Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI From Week 24 to Week 96
Secondary Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis, 29-Item [MSIS-29] Physical Scale The MSIS-29, version 2 is a 29-item patient-reported measure of the physical and psychological impacts of MS. Participants are asked to rate how much their functioning and well-being has been impacted over the past 14 days on a 4-point scale, from "Not at all" (1) to "Extremely" (4). The physical score is the sum of items 1-20, which is then transformed to a 0-100 scale. The psychological score is the sum of items 21-29, transformed to a 0-100 scale. Higher scores indicate a greater impact of MS. Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96
Secondary Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) Score The SDMT is used for detecting the presence of cognitive impairment and changes in cognitive functioning over time and in response to treatment. The SDMT is brief, is easy to administer test, and involves a simple substitution task. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected only orally, and administration time is approximately 5 minutes. The number of correct responses in 90 seconds will be considered the SDMT score. A decrease by 4 points on the SDMT score from baseline represents a clinically meaningful change in cognitive processing. The SDMT score ranges from 0 to 110. The higher the results, the better processing speed/working memory. Minimum of 96 weeks
Secondary Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light chain (NfL) Up to 48 weeks
Secondary Percentage of Participants with Adverse Events (AEs) Up to 4.5 years
Secondary Plasma Concentrations of Fenebrutinib at Specified Timepoints Up to 4.5 years
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