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

Relapsing Multiple Sclerosis Clinical Trial

— FENhance 2  

Official title:

A Phase III Multicenter Randomized, Double-Blind, Double-Dummy, Parallel-Group Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Adult Patients With Relapsing Multiple Sclerosis

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
• 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
• 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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

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