A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- Registration Number
- NCT04586010
- Lead Sponsor
- Hoffmann-La Roche
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 746
- 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.
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.
- 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.
- 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 Exclusion Criteria:
- Acute liver disease
- Chronic liver disease unless considered stable for > 6 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fenebrutinib Fenebrutinib Participants will receive oral fenebrutinib with teriflunomide-matching placebo. Fenebrutinib Placebo Participants will receive oral fenebrutinib with teriflunomide-matching placebo. Teriflunomide Teriflunomide Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion. Teriflunomide Placebo Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion.
- Primary Outcome Measures
Name Time Method Annualized Relapse Rate (ARR) Minimum of 96 weeks
- Secondary Outcome Measures
Name Time Method 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 Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI From Week 24 to Week 96 Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis, 29-Item [MSIS-29] Physical Scale Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96 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.
Time to Onset of 12-week Confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) Score Minimum of 96 weeks 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.
Change from Baseline to Week 48 in the Concentration of Blood Neurofilament Light Chain (NfL) Up to 48 weeks Percentage of Participants with Adverse Events (AEs) Up to 4.5 years Plasma Concentrations of Fenebrutinib at Specified Timepoints Up to 4.5 years Time to Onset of Composite 12-week Confirmed Progression Independent of Relapse Activity (cPIRA12) Minimum of 96 weeks
Trial Locations
- Locations (160)
Inselspital Bern Medizin Neurologie
🇨🇭Bern, Switzerland
Ospedale Regionale di Lugano - Civico
🇨🇭Lugano, Switzerland
Hopital Razi
🇹🇳Mannouba, Tunisia
Fattouma Bourguiba Hospital
🇹🇳Monastir, Tunisia
Hospital Habib Bourguiba
🇹🇳Sfax, Tunisia
MNE Lviv Territorial Medical Association Clinical Hospital for Palliative Care
🇺🇦Lviv, Chernihiv Governorate, Ukraine
Medical Center Dopomoga Plus
🇺🇦Kyiv, Katerynoslav Governorate, Ukraine
LCC "Medical center "Unimed"
🇺🇦Zaporizhia, Katerynoslav Governorate, Ukraine
Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
🇺🇦Zaporizhzhia, Katerynoslav Governorate, Ukraine
SI USSRI of Medical and Social Problems of Disabilities of MOHU
🇺🇦Dnipro, KIEV Governorate, Ukraine
Medical Center of Private Execution First Private Clinic
🇺🇦Kyiv, KIEV Governorate, Ukraine
Salutem Medical Center
🇺🇦Vinnytsia, KIEV Governorate, Ukraine
Medical Clinical Research Center of Medical Center LLC Health Clinic
🇺🇦Vinnytsi, Podolia Governorate, Ukraine
Separated structural unit ?University hospital? of Dnipro State Medical University
🇺🇦Dnipro, Tavria Okruha, Ukraine
Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz
🇩🇪Westerstede, Germany
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Alabama Neurology Associates
🇺🇸Homewood, Alabama, United States
Center for Neurology and Spine - Phoenix - Hunt - PPDS
🇺🇸Phoenix, Arizona, United States
Profound Research, LLC
🇺🇸Carlsbad, California, United States
University of California Irvine
🇺🇸Irvine, California, United States
SC3 Research Group, Inc
🇺🇸Pasadena, California, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Mountain View Clinical Research
🇺🇸Denver, Colorado, United States
Advanced Neurology of Colorado, LLC
🇺🇸Fort Collins, Colorado, United States
Neurology Associates, PA; Research Department
🇺🇸Maitland, Florida, United States
NorthShore University HealthSystem
🇺🇸Highland Park, Illinois, United States
Fort Wayne Neurological Center
🇺🇸Fort Wayne, Indiana, United States
The NeuroMedical Center
🇺🇸Baton Rouge, Louisiana, United States
Ochsner LSU Health
🇺🇸Shreveport, Louisiana, United States
Johns Hopkins University School Of Medicine; Outpatient Center
🇺🇸Baltimore, Maryland, United States
University of Massachusetts Medical School
🇺🇸Worcester, Massachusetts, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Holy Name Hospital; Institute For Clinical Research
🇺🇸Teaneck, New Jersey, United States
University of New Mexico; MS Specialty Clinic
🇺🇸Albuquerque, New Mexico, 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
Oklahoma Medical Research Foundation; MS Center of Excellence
🇺🇸Oklahoma City, Oklahoma, United States
St. Luke's University Health network
🇺🇸Bethlehem, Pennsylvania, United States
Premier Neurology
🇺🇸Greenville, South Carolina, United States
New Orleans Center for Clinical Research
🇺🇸Knoxville, Tennessee, United States
North Texas Institute of Neurology and Headache NextStage Clinical Research Clinic
🇺🇸Plano, Texas, United States
Texas Institute for Neurological Disorders
🇺🇸Sherman, Texas, United States
Multiple Sclerosis Center of Greater Washington
🇺🇸Vienna, Virginia, United States
Evergreen MS Center
🇺🇸Kirkland, Washington, United States
Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders
🇺🇸Milwaukee, Wisconsin, United States
IME - Instituto Médico Especializado
🇦🇷Buenos Aires, Argentina
Centro de Especialidades Neurológicas y Rehabilitación - CENyR
🇦🇷Buenos Aires, Argentina
CIER
🇦🇷C. A. B. A., 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, Argentina
Peking University First Hospital
🇨🇳Beijing City, China
Beijing Tiantan Hospital,Capital Medical University
🇨🇳Beijing, 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
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou City, China
1st Affiliated Hospital of Shanxi Medical University
🇨🇳Taiyuan, 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
🇨🇳Xi'an, China
NeuroINC
🇩🇴Santiago de los Caballeros, Dominican Republic
Hospital Padre Billini
🇩🇴Santo Domingo, Dominican Republic
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
New Hospitals
🇬🇪Tbilisi, Georgia
Pineo Medical Ecosystem
🇬🇪Tbilisi, Georgia
St. Michael hospital
🇬🇪Tbilisi, Georgia
MediClab Georgia
🇬🇪Tbilisi, Georgia
Khechinashvili University Hospital
🇬🇪Tbilisi, Georgia
Jüdisches Krankenhaus Berlin
🇩🇪Berlin, Germany
Studienzentrum Dr. Bischof GmbH
🇩🇪Böblingen, Germany
Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
🇩🇪Dresden, Germany
Universitätsklinikum Gießen und Marburg GmbH
🇩🇪Gießen, Germany
Uniklinik Schleswig-Holstein
🇩🇪Kiel, Germany
Praxis Dr. med. Andreas Kowalik, Arzt für Neurologie und Psychiatrie
🇩🇪Stuttgart, Germany
Universitätsklinikum Tübingen, Zentrum für Neurologie
🇩🇪Tübingen, Germany
Universitätsklinikum Ulm
🇩🇪Ulm, Germany
Pamela Youde Nethersole Eastern Hospital
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰Shatin, New Territories, Hong Kong
Clinexpert Kft.
🇭🇺Budapest, Hungary
S-Medicon Egeszsegugyi Szolgaltato Kft.
🇭🇺Budapest, Hungary
Markhot Ferenc Oktatokorhaz és Rendelointezet
🇭🇺Eger, Hungary
Pest Megyei Flor Ferenc Korhaz
🇭🇺Kistarcsa, Hungary
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
🇭🇺Szeged, Hungary
AOU Seconda Università degli Studi
🇮🇹Napoli, Campania, Italy
AOU Policlinico - Università L. Vanvitelli
🇮🇹Napoli, Campania, Italy
A.O.U. di Parma
🇮🇹Parma, Emilia-Romagna, Italy
Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
🇮🇹Roma, Lazio, Italy
Policlinico Umberto I
🇮🇹Roma, Lazio, Italy
Azienda Ospedaliera Sant'Andrea
🇮🇹Roma, Lazio, Italy
ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla
🇮🇹Bergamo, Lombardia, Italy
IRCCS Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Ospedale Regina Montis Regalis
🇮🇹Mondovì (CN), Piemonte, Italy
AO.U. Policlinico Riuniti Foggia
🇮🇹Foggia, Puglia, Italy
AOU Policlinico V. Emanuele - P.O G. Rodolico
🇮🇹Catania, Sicilia, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Veneto, Italy
Aga Khan University Hospital
🇰🇪Nairobi, Kenya
Clinical Research Institute Saltillo
🇲🇽Saltillo, Coahuila, Mexico
Health Pharma Professional Research
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
Grupo Medico de Investigacion Clinica Multidisciplinaria
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Neurociencias Estudios Clinicos S.C.
🇲🇽Culiacán, Sinaloa, Mexico
Hospital General de Mexico
🇲🇽Mexico, Tlaxcala, Mexico
Zuyderland Medisch Centrum - Sittard Geleen
🇳🇱Sittard-Geleen, Netherlands
PHO General City Hospital 8th September Center for dialysis
🇲🇰Skopje, North Macedonia
University Clinic for Neurology - Skopje
🇲🇰Skopje, North Macedonia
Clinical Hospital Stip
🇲🇰Stip, North Macedonia
Hospital IV Alberto Sabogal Sologuren
🇵🇪Bellavista, Peru
Hospital Nacional Guillermo Almenara Irigoyen
🇵🇪La Victoria, Lima, Peru
Hospital Nacional Dos de Mayo
🇵🇪Lima, Peru
Clinica Internacional Sede Lima
🇵🇪LIma, Peru
Hospital Maria Auxiliadora
🇵🇪Lima, Peru
Clinica Centenario Peruano Japonesa
🇵🇪Pueblo Libre, Peru
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
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, Poland
Hospital Alvaro Cunqueiro
🇪🇸Vigo, Pontevedra, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario de la Princesa
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Ramon y Cajal
🇪🇸Madrid, Spain
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga ? Hospital General
🇪🇸Malaga, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital de Braga
🇵🇹Braga, Portugal
HUC
🇵🇹Coimbra, Portugal
Hospital Santo Antonio dos Capuchos
🇵🇹Lisboa, Portugal
Hospital da Luz
🇵🇹Lisboa, Portugal
Hospital Geral de Santo Antonio
🇵🇹Porto, Portugal
Hospital de Sao Joao
🇵🇹Porto, Portugal
Centro Hospitalar Entre o Douro e Vouga E.P.E. - Hospital de São Sebastião
🇵🇹Santa Maria Da Feira, Portugal
Republican clinical hospital named after G.G. Kuvatov
🇷🇺UFA, Baskortostan, Russian Federation
Leningrad Regional Clinical Hospital
🇷🇺St Petersburg, Sankt Petersburg, Russian Federation
Pavlov State Medical Uni
🇷🇺St Petersburg, Sankt Petersburg, Russian Federation
Ulyanovsk Regional Clinical Hospital
🇷🇺Ulyanovsk, Uljanovsk, Russian Federation
Center of Cardiology and Neurology
🇷🇺Kirov, Russian Federation
FSBIH Siberian Regional Medical Centre of FMBA of Russia
🇷🇺Novosibirsk, Russian Federation
University Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Hospital Universitari de Bellvitge
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Quiron de Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Universitario Virgen de Arrixaca
🇪🇸EL Palmar (EL Palmar), Murcia, Spain
Ams of Ukraine
🇺🇦Kharkov, Ukraine
Lviv Regional Clinical Hospital
🇺🇦Lviv, Ukraine
Odesa Regional Clinical Hospital
🇺🇦Odesa, Ukraine