Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
- Conditions
- Relapsing Multiple Sclerosis
- Interventions
- Registration Number
- NCT04586023
- 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
- 751
- 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 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.
- 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:
- Chronic liver disease unless considered stable for > 6 months
- Acute liver disease
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 Placebo Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion. Teriflunomide Teriflunomide 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 (107)
NCL Institute Neuroscience
🇮🇹Roma, Lazio, Italy
Irccs A.O.U.San Martino Ist
🇮🇹Genova, Liguria, Italy
Fond. Istituto Neurologico C.Besta
🇮🇹Milano, Lombardia, Italy
Ospedale Civile di Montichiari
🇮🇹Montichiari, Lombardia, Italy
IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
🇮🇹Pavia, Lombardia, Italy
IRCCS Istituto Neurologico Neuromed
🇮🇹Pozzilli, Molise, Italy
Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari
🇮🇹Bari, Puglia, Italy
Ospedale Binaghi
🇮🇹Cagliari, Sardegna, Italy
AOU Policlinico Giaccone
🇮🇹Palermo, Sicilia, Italy
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Mexico Centre for Clinical Research
🇲🇽Ciudad de México, Mexico CITY (federal District), Mexico
Clinstile S.A de C.V.
🇲🇽Mexico City, Mexico CITY (federal District), Mexico
Grupo Médico Camino S.C.
🇲🇽Mexico, Mexico CITY (federal District), Mexico
Unidad de Investigación en Salud
🇲🇽Chihuahua, Mexico
Unidad de investigacion en salud (UIS)
🇲🇽Ciudad de México, Mexico
NZOZ Vitamed
🇵🇱Bydgoszcz, Poland
Neurocentrum Bydgoszcz sp. z o.o
🇵🇱Bydgoszcz, Poland
COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika
🇵🇱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, Poland
Krasnoyarsk State Medical Academy
🇷🇺Krasnoyarsk, Krasnojarsk, Russian Federation
FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
🇷🇺Krasnoyarsk, Krasnojarsk, Russian Federation
National Center of Social Significant Disease
🇷🇺Sankt-peterburg, Leningrad, Russian Federation
Federal center of brain research and neurotechnologies
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Regional Clinical Hospital N.A. Semashko
🇷🇺Nizhny Novgorod, Niznij Novgorod, Russian Federation
Regional clinical hospital named after prof. S.V. Ochapovsky
🇷🇺Krasnodar, Russian Federation
Nebbiolo Center for Clinical Trials
🇷🇺Tomsk, Russian Federation
Gazi University Medical Faculty
🇹🇷Ankara, Turkey
Bakirkoy State Mental Hospital
🇹🇷Istanbul, Turkey
Sancaktepe Training and Research Hospital
🇹🇷Istanbul, Turkey
Selcuk University Medical Faculty
🇹🇷Istanbul, Turkey
Kocaeli University Hospital
🇹🇷Kocaeli, Turkey
North Central Neurology Associates
🇺🇸Cullman, Alabama, United States
Xenoscience
🇺🇸Phoenix, Arizona, United States
Los Angeles Biomedical Research Institute at Harbor-UCLA
🇺🇸Torrance, California, United States
KI Health Partners, LLC
🇺🇸Stamford, Connecticut, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
University of South Florida
🇺🇸Tampa, Florida, United States
American Health Network Institute, LLC
🇺🇸Avon, Indiana, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Neuro Institute of New England P.C.
🇺🇸Foxboro, Massachusetts, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Hope Neurology
🇺🇸Knoxville, Tennessee, United States
Integrated Neurology Services PLLC
🇺🇸Falls Church, Virginia, United States
Medical College of Wisconsin, Inc.
🇺🇸Milwaukee, Wisconsin, United States
Kepler Universitätskliniken GmbH - Med Campus III
🇦🇹Linz, Austria
L2 Ip Instituto de Pesquisas Clinicas Ltda ME
🇧🇷Brasilia, Distrito Federal, Brazil
Santa Casa de Misericordia
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Instituto de Neurologia de Curitiba
🇧🇷Curitiba, Paraná, Brazil
IMV Pesquisa Neurológica
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Núcleo de Pesquisa do Rio Grande do Sul
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Clinica Neurologica
🇧🇷Joinville, Santa Catarina, Brazil
Praxis Pesquisa Médica
🇧🇷Santo Andre, São Paulo, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clínicos
🇧🇷Sao Bernardo Do Campo, São Paulo, Brazil
Centro de Pesquisas Clinicas
🇧🇷Sao Paulo, São Paulo, Brazil
Hospital Santa Marcelina
🇧🇷Sao Paulo, São Paulo, Brazil
Jordy Sinapse Medicina LTDA ME
🇧🇷São Paulo, Brazil
UMHAT Dr. Georgi Stranski
🇧🇬Pleven, Bulgaria
MHATNP Sveti Naum EAD
🇧🇬Sofia, Bulgaria
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
The Ottawa Hospital - General Campus
🇨🇦Ottawa, Ontario, Canada
CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital
🇨🇦Chicoutimi, Quebec, Canada
MUCH - Montreal Neurological Institute & Hospital
🇨🇦Montreal, Quebec, Canada
CHU de Québec
🇨🇦Quebec City, Quebec, Canada
Sydvestjysk Sygehus Esbjerg
🇩🇰Esbjerg, Denmark
Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken
🇩🇰Sønderborg, Denmark
Hopital Gabriel Montpied CHU de Clermont-Ferrand
🇫🇷Clermont-Ferrand, France
Hôpital Pasteur
🇫🇷Nice, France
Hôpital Charles Nicolle
🇫🇷Rouen, France
Hospital Eginition
🇬🇷Athens, Greece
University General Hospital of Larisa
🇬🇷Larisa, Greece
AHEPA Univ. General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Nucare
🇬🇹Ciudad Guatemala, Guatemala
Max Super Speciality Hospital
🇮🇳New Delhi, Delhi, India
Sir Gangaram Hospital
🇮🇳New Delhi, Delhi, India
Zydus Hospital
🇮🇳Ahmadabad CITY, Gujarat, India
Seth G.S Medical College K.E.M Hospital
🇮🇳Mumbai, Maharashtra, India
Sahyadri Superspeciality Hospital
🇮🇳Pune City, Maharashtra, India
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳Pune, Maharashtra, India
Christian Medical College and Hospital
🇮🇳Ludhiana, Punjab, India
SRM Institute of Medical Sciences
🇮🇳Vadapalani, Tamil NADU, India
Postgraduate Institute of Medical Education and Research
🇮🇳Chandigarh, India
Universita? G. D'Annunzio
🇮🇹Chieti, Abruzzo, Italy
A. O. U. Federico II
🇮🇹Napoli, Campania, Italy
Ospedale S.Camillo Forlanini
🇮🇹Roma, Lazio, Italy
Policlinico Universitario A. Gemelli
🇮🇹Roma, Lazio, Italy
Ege Üniversitesi Tip Fakültesi
🇹🇷Lzmir, Turkey
Mersin University Medical Faculty
🇹🇷Mersin, Turkey
Ondokuz Mayis University School of Medicine
🇹🇷Samsun, Turkey
Karadeniz Tecnical Uni. Med. Fac.
🇹🇷Trabzon, Turkey
Van Yuzuncu Yil University Hospital
🇹🇷Van, Turkey
Baskent Universitesi Ankara Hastanesi
🇹🇷Çankaya, Turkey
Salford Royal NHS Foundation Trust
🇬🇧Salford, United Kingdom