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

Relapsing Multiple Sclerosis Clinical Trial

— FENhance  

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: NCT04586010
• Other study ID #: GN41851
• Secondary ID: 2019-004857-1020
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 17, 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: 746
• 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 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.
• 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
Argentina	Centro de Especialidades Neurológicas y Rehabilitación - CENyR	Buenos Aires
Argentina	CIER	C. A. B. A.
Argentina	NeuroSite	Ciudad Autonoma Buenos Aires
Argentina	Instituto de Investigaciones Metabolicas (Idim)	Ciudad Autonoma de Buenos Aires
Argentina	Diagnostico Medico Oroño	Rosario
Argentina	Cer San Juan	San Juan
Argentina	Centro de Investigaciones Médicas Tucuman	San Miguel de Tucuman
China	Beijing Tiantan Hospital,Capital Medical University	Beijing City
China	Peking University First Hospital	Beijing City
China	the First Hospital of Jilin University	Changchun
China	Xiangya Hospital Central South University	Changsha City
China	West China Hospital, Sichuan University	Chengdu
China	The First Affiliated Hospital, Chongqing Medical University	Chongqing
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou City
China	The second Affiliated Hospital of Guangzhou Medical University	Guangzhou City
China	The affiliated Hospital of Guiyang Medical College	Guiyang
China	The First People?s Hospital of Yunnan Province	Kunming City
China	Lanzhou University Second Hospital	Lanzhou
China	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City
China	Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai
China	The Second Hospital of Hebei Medical University	Shijiazhuang
China	The First Affiliated Hospital of Soochow University; Neurology department	Suzhou City
China	1st Affiliated Hospital of Shanxi Medical University	Taiyuan City
China	Tianjin Medical University General Hospital	Tianjin
China	Xinjiang People Hospital	Urumqi City
China	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	Tangdu Hospital, The Fourth Military Medical University; Neurology Department	Xi'an City
Dominican Republic	NeuroINC	Santiago de los Caballeros
Dominican Republic	Hospital Padre Billini	Santo Domingo
Finland	Helsinki University Central Hospital; Department of Neurology	Helsinki
Georgia	Archangel St. Michael Multiprofile Clinical Hospital	Tbilisi
Georgia	Khechinashvili University Hospital; Neurological Department	Tbilisi
Georgia	MediClab Georgia	Tbilisi
Georgia	New Hospitals; Neurology and Neurorehabilitation	Tbilisi
Georgia	Pineo Medical Ecosystem; Neurological Department	Tbilisi
Germany	Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie	Berlin
Germany	Studienzentrum für Neurologie und Psychiatrie	Böblingen
Germany	Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften	Dresden
Germany	Universitätsklinikum Gießen und Marburg GmbH; Neurologie	Gießen
Germany	Uniklinik Schleswig-Holstein; Neuroimmunologie, Institut für Klinische Chemie + Klinik f. Neurologie	Kiel
Germany	Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie	Münster
Germany	Nordwest-Krankenhaus Sanderbusch gGMBH; Neurologische Klinik	Sande
Germany	Praxis Dr. med. Andreas Kowalik, Arzt für Neurologie und Psychiatrie	Stuttgart
Germany	Universitätsklinikum Tübingen, Zentrum für Neurologie	Tübingen
Germany	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm
Germany	Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz	Westerstede
Hong Kong	Pamela Youde Nethersole Eastern Hospital; Department of Medicine	Hong Kong
Hong Kong	Prince of Wales Hospital; Division of Neurology, Department of Medicine and Therapeutics	Shatin, New Territories
Hungary	Clinexpert Kft.	Budapest
Hungary	S-Medicon Egeszsegugyi Szolgaltato Kft.	Budapest
Hungary	Markhot Ferenc Oktatokorhaz és Rendelointezet; Neurologiai és Stroke Osztaly	Eger
Hungary	Pest Megyei Flor Ferenc Korhaz	Kistarcsa
Hungary	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika	Szeged
Italy	ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla	Bergamo	Lombardia
Italy	AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla	Catania	Sicilia
Italy	AOUC Azienda Ospedaliero-Universitaria Careggi; Neurologia 2	Firenze	Toscana
Italy	AO.U. Policlinico Riuniti Foggia; Neurologia Univ.-Centro intradip. malattie demielinizzanti	Foggia	Puglia
Italy	Ospedale San Salvatore; Clinica Neurologica - Centro Sclerosi Multipla	L'Aquila	Abruzzo
Italy	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia
Italy	Ospedale Regina Montis Regalis; SC Neurologia, Centro Sclerosi Multipla	Mondovì (CN)	Piemonte
Italy	AOU Policlinico - Università L. Vanvitelli; D.A.I. di Medicina Interna e Specialistica	Napoli	Campania
Italy	AOU Seconda Università degli Studi; Dip. Assistenziale Integrato Medicina Int-II Clinica Neurologica	Napoli	Campania
Italy	Azienda Ospedaliera di Padova; Clinica Neurologica	Padova	Veneto
Italy	A.O.U. di Parma; SC Neurologia, Amb. Sclerosi Multipla (malattie demielinizzanti)	Parma	Emilia-Romagna
Italy	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio
Italy	Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla	Roma	Lazio
Italy	Policlinico Umberto I; Centro Sclerosi Multipla DAI Neuroscienze e Salute Mentale	Roma	Lazio
Italy	AOU Senese - Presidio Ospedaliero Le Scotte; UOSA Neurologia Sperimentale	Siena	Toscana
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona	Torrette - Ancona	Marche
Kenya	Aga Khan University Hospital	Nairobi
Mexico	Health Pharma Professional Research	Cdmx	Mexico CITY (federal District)
Mexico	Neurociencias Estudios Clinicos S.C.	Culiacán	Sinaloa
Mexico	Hospital General de Mexico	Mexico	Tlaxcala
Mexico	Grupo Medico de Investigacion Clinica Multidisciplinaria	Mexico City	Mexico CITY (federal District)
Mexico	Clinical Research Institute Saltillo	Saltillo	Coahuila
Netherlands	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen
North Macedonia	PHO General City Hospital 8th September Center for dialysis	Skopje
North Macedonia	University Clinic for Neurology - Skopje	Skopje
North Macedonia	Clinical Hospital Stip	Stip
Peru	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista
Peru	HOSPITAL NACIONAL GUILLERMO ALMENARA IRIGOYEN; Unidad de Investigacion en Neurologia	La Victoria, Lima
Peru	Clinica Internacional Sede Lima	LIma
Peru	Hospital Maria Auxiliadora	Lima
Peru	Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia	Lima
Peru	Clinica Centenario Peruano Japonesa; Neurology	Pueblo Libre
Poland	ProNeuro Centrum Medyczne	?ory
Poland	Neurocentrum Bydgoszcz sp. z o.o	Bydgoszcz
Poland	Care Clinic	Katowice
Poland	MT Medic Krosno	Krosno
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	Rodzinne Centrum Medyczne Lubimed.pl	Lublin
Poland	Wojewodzki Szpital Specjalistyczny im. Sw. Jadwigi Slaskiej; Oddzia? Neurologii	Opole
Poland	Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych	Plewiska
Poland	MedPolonia	Poznan
Poland	Instytut Psychiatrii i Neurologii II Klinika Neurologiczna	Warszawa
Poland	IBISMED Wielospecjalistyczne Centrum Medyczne	Zabrze
Portugal	Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)	Braga
Portugal	HUC; Servico de Neurologia	Coimbra
Portugal	Hospital da Luz; Neurologia	Lisboa
Portugal	Hospital Santo Antonio dos Capuchos; Servico de Neurologia	Lisboa
Portugal	Hospital de Sao Joao; Servico de Neurologia	Porto
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Portugal	Centro Hospitalar Entre o Douro e Vouga E.P.E. - Hospital de São Sebastião; Servilo de Neurologia	Santa Maria Da Feira
Russian Federation	Center of Cardiology and Neurology	Kirov
Russian Federation	FSBIH Siberian Regional Medical Centre of FMBA of Russia	Novosibirsk
Russian Federation	N.P. Bechtereva Institute of the Human Brain	Sankt-petersburg	Sankt Petersburg
Russian Federation	Leningrad Regional Clinical Hospital	St Petersburg	Sankt Petersburg
Russian Federation	Pavlov State Medical Uni ; Neurology	St Petersburg	Sankt Petersburg
Russian Federation	Republican clinical hospital named after G.G. Kuvatov	UFA	Baskortostan
Russian Federation	Ulyanovsk Regional Clinical Hospital	Ulyanovsk	Uljanovsk
Serbia	University Clinical Center of Serbia; Clinic of neurology	Belgrade
Spain	Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia	Barcelona
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Neurología	EL Palmar (EL Palmar)	Murcia
Spain	Hospital Universitari de Bellvitge; Servicio de Neurologia	L'Hospitalet de Llobregat	Barcelona
Spain	Fundacion Jimenez Diaz; Servicio de Neurología	Madrid
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Neurologia	Madrid
Spain	Hospital Ramon y Cajal; Servicio de Neurologia	Madrid
Spain	Hospital Universitario de la Princesa; Servicio de Neurologia	Madrid
Spain	Hospital Regional Universitario de Malaga ? Hospital General; Servicio de Neurologia	Malaga
Spain	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Virgen Macarena; Servicio de Neurologia	Sevilla
Spain	Hospital Alvaro Cunqueiro; Servicio de Neurologia	Vigo	Pontevedra
Switzerland	Inselspital Bern Medizin Neurologie; Neurologische Poliklinik	Bern
Switzerland	Ospedale Regionale di Lugano - Civico; Neurologia	Lugano
Tunisia	Hopital Razi; Neurology Department	Mannouba
Tunisia	Fattouma Bourguiba Hospital	Monastir
Tunisia	Hospital Habib Bourguiba	Sfax
Ukraine	Separated structural unit ?University clinic? of Dnipro State Medical University	Dnipro	Kharkiv Governorate
Ukraine	SI USSRI of Medical and Social Problems of Disabilities of MOHU	Dnipro	KIEV Governorate
Ukraine	Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology	Kharkov
Ukraine	Medical Center Dopomoga Plus	Kyiv	Chernihiv Governorate
Ukraine	Medical Center of Private Execution First Private Clinic	Kyiv	KIEV Governorate
Ukraine	Lviv Regional Clinical Hospital; Department of Neurology	Lviv
Ukraine	MNE Lviv Territorial Medical Association Clinical Hospital for Palliative Care	Lviv	Chernihiv Governorate
Ukraine	Odesa Regional Clinical Hospital; Neurosurgery Department	Odesa
Ukraine	Medical Clinical Research Center of Medical Center LLC Health Clinic	Vinnytsia	Podolia Governorate
Ukraine	Salutem Medical Center	Vinnytsia	KIEV Governorate
Ukraine	Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council	Zaporizhzhia	Katerynoslav Governorate
Ukraine	Zaporizhia City Multispecialty Clinical Hospital #9	Zaporizhzhye	Katerynoslav Governorate
United States	University of New Mexico; MS Specialty Clinic	Albuquerque	New Mexico
United States	University of Colorado Denver	Aurora	Colorado
United States	Johns Hopkins University School Of Medicine; Outpatient Center	Baltimore	Maryland
United States	The NeuroMedical Center	Baton Rouge	Louisiana
United States	St. Luke's University Health network	Bethlehem	Pennsylvania
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Profound Research, LLC	Carlsbad	California
United States	Miami Valley Hospital South; Dayton Physician's Office	Centerville	Ohio
United States	OhioHealth	Columbus	Ohio
United States	The Boster Center for MS	Columbus	Ohio
United States	Mountain View Clinical Research	Denver	Colorado
United States	Henry Ford Health System	Detroit	Michigan
United States	Advanced Neurology of Colorado, LLC	Fort Collins	Colorado
United States	Fort Wayne Neurological Center	Fort Wayne	Indiana
United States	Premier Neurology	Greenville	South Carolina
United States	NorthShore University HealthSystem	Highland Park	Illinois
United States	Alabama Neurology Associates	Homewood	Alabama
United States	University of California Irvine	Irvine	California
United States	Evergreen MS Center	Kirkland	Washington
United States	New Orleans Center for Clinical Research	Knoxville	Tennessee
United States	Neurology Associates, PA; Research Department	Maitland	Florida
United States	Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders	Milwaukee	Wisconsin
United States	Oklahoma Medical Research Foundation; MS Center of Excellence	Oklahoma City	Oklahoma
United States	SC3 Research Group, Inc	Pasadena	California
United States	Center for Neurology and Spine - Phoenix - Hunt - PPDS	Phoenix	Arizona
United States	North Texas Institute of Neurology and Headache NextStage Clinical Research Clinic	Plano	Texas
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Texas Institute for Neurological Disorders	Sherman	Texas
United States	Ochsner LSU Health	Shreveport	Louisiana
United States	Holy Name Hospital; Institute For Clinical Research	Teaneck	New Jersey
United States	Multiple Sclerosis Center of Greater Washington	Vienna	Virginia
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  China,  Dominican Republic,  Finland,  Georgia,  Germany,  Hong Kong,  Hungary,  Italy,  Kenya,  Mexico,  Netherlands,  North Macedonia,  Peru,  Poland,  Portugal,  Russian Federation,  Serbia,  Spain,  Switzerland,  Tunisia,  Ukraine, 

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