A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis
FENtrepid
A Phase III Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel-Group Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Patients With Primary Progressive Multiple Sclerosis.
3 other identifiers
interventional
985
27 countries
182
Brief Summary
A study to evaluate the efficacy and safety of fenebrutinib on disability progression in adult participants with Primary Progressive Multiple Sclerosis (PPMS). All eligible participants will be randomized 1:1 to either daily oral fenebrutinib (and placebo) or intravenous (IV) ocrelizumab (and placebo) in a blinded fashion through an interactive voice or web-based response system (IxRS). 985 participants were enrolled and recruited globally. Participants who discontinue study medication early or discontinue from the study will not be replaced. The Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis of the study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Oct 2020
Longer than P75 for phase_3
182 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 4, 2020
CompletedFirst Posted
Study publicly available on registry
September 10, 2020
CompletedStudy Start
First participant enrolled
October 26, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 17, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 21, 2027
ExpectedMarch 27, 2026
March 1, 2026
4.9 years
September 4, 2020
March 24, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)
Minimum of 120 weeks
Secondary Outcomes (9)
Time to Onset of Composite 24-week CDP (cCDP24)
Minimum of 120 weeks
Time to Onset of 12-week CDP (CDP12)
Minimum of 120 weeks
Time to Onset of 24-week CDP (CDP24)
Minimum of 120 weeks
Percentage Change in Total Brain Volume Assessed by Magnetic Resonance Imaging (MRI)
From Week 24 to Week 120
Change from Baseline in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis Impact Scale, 29-Item [MSIS-29] Physical Scale
Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
- +4 more secondary outcomes
Study Arms (2)
Fenebrutinib
EXPERIMENTALParticipants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.
Ocrelizumab
ACTIVE COMPARATORParticipants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.
Interventions
Participants will receive ocrelizumab-matching placebo.
Participants will receive fenebrutinib-matching placebo
Eligibility Criteria
You may qualify if:
- For sites in Germany and Italy only, enrollment is restricted to participants aged 46-65 years
- A diagnosis of PPMS in accordance to the revised 2017 McDonald Criteria (Thompson et al. 2018).
- Disability progression in the 12 months prior to screening.
- Expanded Disability Status Scale (EDSS) score from 3.0 to 6.5 inclusive at screening.
- Pyramidal functional subscore \>=2 at screening.
- For participants currently receiving proton pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), symptomatic treatment for MS (e.g. fampridine, cannabis) and/or physiotherapy: treatment at a stable dose during the screening period prior to the initiation of study treatment and plans to remain at a stable dose for the duration of study treatment.
- Neurologically stable for at least 30 days prior to randomization and baseline assessments.
- Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in \<240 seconds.
- Ability to perform 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.
- 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.
- 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.
You may not qualify if:
- For participants enrolled in Germany and in Italy only: Presence of gadolinium-enhancing lesions on T1-weighted MRI (T1Gd +) lesion on the screening MRI
- Any known or suspected active infection (excluding onychomycosis) 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).
- Participants with a previous history of a serious Infusion-Related Reaction (IRR) (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade \>= 4) and/or any hypersensitivity reaction to ocrelizumab.
- History of cancer including hematologic malignancy and solid tumors within 10 years of screening. Exceptions: Basal/squamous cell carcinoma of skin cured by excision. In situ carcinoma of the cervix successfully treated by curative therapy \>1 year prior to screening.
- Known presence of other neurological disorders, that could interfere with the diagnosis of MS or assessments of efficacy or safety during the study, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
- Presence of cirrhosis (Child-Pugh Class A, B, or C)
- Chronic liver disease unless considered stable for \>6 months
- Acute liver disease
- Any concomitant disease that may require chronic treatment with systemic corticosteroids, immunosuppressants or specific medication that could impact the primary evaluation of the study.
- History of alcohol or other drug abuse within 12 months prior to screening.
- Female participants who are pregnant or breastfeeding or intending to become pregnant during the study or 6 or 12 months (as applicable from the local label for ocrelizumab) after final dose of study drug.
- Male participants intending to father a child during the study or for 28 days after final dose of study drug.
- Lack of peripheral venous access.
- Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period.
- Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization.
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (189)
Alabama Neurology Associates
Homewood, Alabama, 35209, United States
Sutter East Bay Medical Foundation
Berkeley, California, 94705, United States
Fullerton Neurology and Headache Center
Fullerton, California, 92835, United States
Palo Alto Medical Foundation Research Center
Sunnyvale, California, 94086, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Yale University School Of Medicine
Fairfield, Connecticut, 06824, United States
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007, United States
Neurology Associates PA
Maitland, Florida, 32751, United States
Neurological Services of Orlando
Orlando, Florida, 32806, United States
University of South Florida
Tampa, Florida, 33612, United States
Josephson Wallack Munshower Neurology PC
Indianapolis, Indiana, 46256, United States
University of Kansas Medical Center
Kansas City, Kansas, 66160, United States
Johns Hopkins University School Of Medicine
Baltimore, Maryland, 21287, United States
Dragonfly Research, LLC
Wellesley, Massachusetts, 02481, United States
Wayne State University
Detroit, Michigan, 48201, United States
Minneapolis Clinic of Neurology
Golden Valley, Minnesota, 55422, United States
Washington University
St Louis, Missouri, 63128, United States
Cleveland Clinic Lou Ruvo
Las Vegas, Nevada, 89106, United States
Hackensack U Med Ctr
Hackensack, New Jersey, 07601, United States
Barnabas Health Ambulatory Care Center
Livingston, New Jersey, 07039, United States
Jersey Shore University Medical Centre
Neptune City, New Jersey, 07753, United States
Rutgers New Jersey Medical School
Newark, New Jersey, 07103, United States
Holy Name Hospital
Teaneck, New Jersey, 07666, United States
Dent Neurological Institute
Amherst, New York, 14226, United States
Columbia University Medical Center
New York, New York, 10032, United States
University of Rochester
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794, United States
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Atrium Health Neurosciences Institute ? Charlotte
Charlotte, North Carolina, 28204, United States
Raleigh Neurology Associates
Raleigh, North Carolina, 27607-6520, United States
Miami Valley Hospital South
Centerville, Ohio, 45459, United States
UC Health, LLC.
Cincinnati, Ohio, 45267, United States
OhioHealth Riverside Methodist Hospital
Columbus, Ohio, 43214, United States
Providence Brain and Spine Institute
Portland, Oregon, 97225, United States
Neurology Clinic PC
Cordova, Tennessee, 38018, United States
Hope Neurology
Knoxville, Tennessee, 37922, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Uni of Texas Health Science Center At Houston
Houston, Texas, 77030, United States
Texas Institute for Neurological Disorders
Sherman, Texas, 75092, United States
Evergreen MS Center
Kirkland, Washington, 98034, United States
Swedish Medical Center
Seattle, Washington, 98122, United States
West Virginia University
Morgantown, West Virginia, 26506, United States
Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, 53226-3596, United States
Centro de Especialidades Neurológicas y Rehabilitación - CENyR
Buenos Aires, C1424, Argentina
Focus CECIC
Buenos Aires, Argentina
Instituto Reumatológico Strusberg
Córdoba, X5000EDC, Argentina
Fundacion Rosarina de Neurorehabilitacion
Rosario, 2000, Argentina
Centro de Investigaciones Médicas Tucuman
San Miguel, T4000AXL, Argentina
Brain and Mind Research Institute
Camperdown, New South Wales, 2050, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
John Hunter Hospital
New Lambton, New South Wales, 2305, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
Austin Hospital
Heidelberg, Victoria, 3084, Australia
Royal Melbourne Hospital
Parkville, Victoria, 3050, Australia
Kepler Universitätsklinikum GmbH - Neuromed Campus
Linz, 4020, Austria
Medizinische Universität Wien
Vienna, 1090, Austria
Santa Casa de Misericordia
Belo Horizonte, Minas Gerais, 30150-221, Brazil
Instituto de Neurologia de Curitiba
Curitiba, Paraná, 81210-310, Brazil
Núcleo de Pesquisa do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90430-001, Brazil
IMV Pesquisa Neurológica
Porto Alegre, Rio Grande do Sul, 90620-130, Brazil
Clinica Neurologica
Joinville, Santa Catarina, 89201-165, Brazil
Centro de Pesquisas Clinicas
São Paulo, São Paulo, 01228-200, Brazil
Hospital Universitario Gaffree e Guinle
Rio de Janeiro, 20270-004, Brazil
UMHAT Dr. Georgi Stranski
Pleven, 5800, Bulgaria
Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD
Sofia, 1113, Bulgaria
University of Alberta Hospital
Edmonton, Alberta, T6G 1Z1, Canada
Fraser Health Authority - Fraser Health Multiple Sclerosis
Burnaby, British Columbia, V5G 2X6, Canada
University of British Columbia
Vancouver, British Columbia, V6T 1Z3, Canada
London Health Sciences Centre Uni Campus
London, Ontario, N6A 5A5, Canada
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6, Canada
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5, Canada
St. Michael's Hospital
Toronto, Ontario, M5B-1W8, Canada
Clinique NeuroOutaouais
Gatineau, Quebec, J8Y 1W2, Canada
Recherche Sepmus Inc.
Greenfield Park, Quebec, J4V 2J2, Canada
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4, Canada
CeCim Biocinetic
Santiago, 8331143, Chile
Clinica Alemana
Vitacura, 0, Chile
Organizacion Sanitas Internacional
Bogotá, Colombia
Fundacion Clinica Valle del Lili
Cali, Colombia
Instituto Neurologico de Colombia INDEC
Medellín, Colombia
Aarhus Universitetshospital
Aarhus N, 8200, Denmark
Rigshospitalet
Glostrup Municipality, 2600, Denmark
Groupe Hospitalier Pellegrin
Bordeaux, 33076, France
Hopital Pierre Wertheimer
Bron, 69677, France
CHRU de Montpellier, Hopital Gui de Chauliac
Montpellier, 34295, France
Hopital Guillaume Et Rene Laennec
Nantes, 44805, France
Hôpital Pasteur
Nice, 06002, France
Hopitaux Universitaires de Strasbourg
Strasbourg, 67091, France
Charite - Universitatsmedizin Berlin
Berlin, 10117, Germany
Studienzentrum Dr. Bischof GmbH
Böblingen, 71034, Germany
Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
Dresden, 01307, Germany
Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie
Freiburg im Breisgau, 79106, Germany
Klinikum rechts der Isar der TU Muenchen
München, 81675, Germany
Universitaetsklinikum Tuebingen
Tübingen, 72076, Germany
Deutsche Klinik für Diagnostik
Wiesbaden, 65191, Germany
Hospital Eginition
Athens, 115 28, Greece
401 Military Hospital of Athens
Athens, 11525, Greece
AHEPA Univ. General Hospital of Thessaloniki
Thessaloniki, 54636, Greece
Clinexpert Kft.
Budapest, 1033, Hungary
S-Medicon Egeszsegugyi Szolgaltato Kft.
Budapest, 1044, Hungary
Budapesti Jahn Ferenc Dél-pesti Kórház és Rendel?intézet
Budapest, 1204, Hungary
Markhot Ferenc Oktatokorhaz és Rendelointezet
Eger, 3300, Hungary
Pest Megyei Flor Ferenc Korhaz
Kistarcsa, 2143, Hungary
Rambam Medical Center
Haifa, 3109601, Israel
The Chaim Sheba Medical Center
Ramat Gan, 5262100, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
AOU Seconda Università degli Studi
Naples, Campania, 80138, Italy
A.O.U. di Parma
Parma, Emilia-Romagna, 43126, Italy
Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
Rome, Lazio, 00133, Italy
Irccs A.O.U.San Martino Ist
Genoa, Liguria, 16132, Italy
IRCCS Ospedale San Raffaele
Milan, Lombardy, 20132, Italy
Ospedale Civile di Montichiari
Montichiari, Lombardy, 25018, Italy
IRCCS Istituto Neurologico Neuromed
Pozzilli, Molise, 86077, Italy
A.R.N.A.S. Civico Di Cristina Benfratelli
Palermo, Sicily, 90127, Italy
Mexico Centre for Clinical Research
Mexico City, Mexico CITY (federal District), 03100, Mexico
Clinstile S.A de C.V.
Mexico City, Mexico CITY (federal District), 06700, Mexico
Hospital Juarez de Mexico
Mexico City, Mexico CITY (federal District), 07760, Mexico
Grupo Médico Camino S.C.
México, Mexico CITY (federal District), 03600, Mexico
Clinical Research Institute
Tialnepantla, Mexico, 54055, Mexico
University Clinic of Neurology
Skopje, 1000, North Macedonia
Hospital IV Alberto Sabogal Sologuren
Bellavista, Callao 2, Peru
Clinica Internacional
Lima, 15001, Peru
Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo
Lima, Lima 01, Peru
Neurocentrum Bydgoszcz sp. z o.o
Bydgoszcz, 85-796, Poland
Care Clinic
Katowice, 40-568, Poland
NEURO-CARE Sp. z o.o. Sp. Komandytowa
Katowice, 40-749, Poland
Centrum Neurologii Krzysztof Selmaj
Lodz, 90-324, Poland
Med Polonia
Późna, 60-693, Poland
Centrum Medyczne "MEDYK"
Rzeszów, 35-055, Poland
Nmedis sp. z o.o.
Rzeszów, 35-323, Poland
Centrum Medyczne NeuroProtect
Warsaw, 01-684, Poland
Wro Medica
Wroc?aw, 51-685, Poland
SPSK nr 1
Zabrze, 41-800, Poland
Hospital de Braga
Braga, 4710-243, Portugal
Hospital Santo Antonio dos Capuchos
Lisbon, 1169-050, Portugal
Hospital de Santa Maria
Lisbon, 1649-035, Portugal
Hospital Geral de Santo Antonio
Porto, 4099-001, Portugal
Hospital de Sao Joao
Porto, 4200-319, Portugal
San Juan MS Center
Guaynabo, 968, Puerto Rico
Krasnoyarsk State Medical Academy
Krasnoyarsk, Krasnoyarsk Krai, 660022, Russia
FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
Krasnoyarsk, Krasnoyarsk Krai, 660037, Russia
Federal center of brain research and neurotechnologies
Moskva, Moscow Oblast, 117997, Russia
City Clinical Hospital #24
Moskva, Moscow Oblast, 127015, Russia
National Center of Social Significant Disease
Saint Petersburg, Sankt-Peterburg, 197110, Russia
City Hospital #40 of Resort Administrative District
Saint Petersburg, Sankt-Peterburg, 197706, Russia
Sverdlovsk Regional Clinical Hospital 1
Yekaterinburg, Sverdlovsk Oblast, 620102, Russia
Vertebronevrologiya LLC
Kazan', Tatarstan Republic, 420047, Russia
Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik
Tyumen, Tyumen Oblast, 625048, Russia
Center of Cardiology and Neurology
Kirov, 610007, Russia
State Novosibirsk Regional Clinical Hospital
Novosibirsk, 630087, Russia
Complejo Hospitalario Universitario A Coruña (CHUAC)
A Coruña, LA Coruna, 15006, Spain
Hospital Universitari Arnau de Vilanova de Lleida
Lleida, Lerida, 25198, Spain
Hospital Quiron de Madrid
Pozuelo de Alarcón, Madrid, 28223, Spain
Hospital Alvaro Cunqueiro
Vigo, Pontevedra, 36213, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Puerta del Mar
Cadiz, 11009, Spain
Hospital Ramon y Cajal
Madrid, 28034, Spain
Hospital Regional Universitario de Malaga ? Hospital General
Málaga, 29010, Spain
Hospital Universitario Virgen Macarena
Seville, 41009, Spain
Universitätsspital Basel
Basel, 4031, Switzerland
Inselspital Bern Medizin Neurologie
Bern, 3010, Switzerland
Hacettepe University Medical Faculty
Ankara, 06100, Turkey (Türkiye)
Baskent Universitesi Ankara Hastanesi
Çankaya, 06490, Turkey (Türkiye)
Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi
Istanbul, 34098, Turkey (Türkiye)
Sancaktepe Training and Research Hospital
Istanbul, 34785, Turkey (Türkiye)
Selcuk University Medical Faculty
Istanbul, 42131, Turkey (Türkiye)
Kocaeli University Hospital
Kocaeli, 41380, Turkey (Türkiye)
Mersin University Medical Faculty
Mersin, 33079, Turkey (Türkiye)
Ondokuz Mayis Univ. Med. Fac.
Samsun, 55139, Turkey (Türkiye)
Karadeniz Tecnical Uni. Med. Fac.
Trabzon, 61080, Turkey (Türkiye)
Van Yuzuncu Yil University Hospital
Van, 65080, Turkey (Türkiye)
CNPE City Clinical Hospital #3 of Chernivtsi City Council
Chernivtsi, Chernihiv Governorate, 58022, Ukraine
Medical Centre of PE First Private Clinic
Zhytomyr, Crimean Regional Governmenta, 10008, Ukraine
Ams of Ukraine
Kharkiv, Kharkiv Governorate, 61068, Ukraine
Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
Zaporizhzhia, Kharkiv Governorate, 69600, Ukraine
MEDBUD
Kyiv, KIEV Governorate, 03037, Ukraine
Lviv Regional Clinical Hospital
Lviv, KIEV Governorate, 79010, Ukraine
Salutem Medical Center
Vinnytsia, KIEV Governorate, 21009, Ukraine
Separated structural unit ?University hospital? of Dnipro State Medical University
Dnipro, Tavria Okruha, Ukraine
Regional Clinical Hospital
Ivano-Frankivsk, 76008, Ukraine
Volyn Regional Clinical Hospital
Lutsk, 43024, Ukraine
"Neurofocus" LLC
Lviv, 79029, Ukraine
Odesa Regional Clinical Hospital
Odesa, 65117, Ukraine
Medical Clinical Research Center of Medical Center LLC Health Clinic
Vinnytsia, 21009, Ukraine
Queen Elizabeth University Hospital
Glasgow, G51 4TF, United Kingdom
Charing Cross Hospital
London, W6 8RF, United Kingdom
Nottingham University Hospitals NHS Trust
Nottingham, NG7 2UH, United Kingdom
Morriston Hospital
Swansea, SA6 6NL, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Sponsor will also be blinded.
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 4, 2020
First Posted
September 10, 2020
Study Start
October 26, 2020
Primary Completion
September 17, 2025
Study Completion (Estimated)
July 21, 2027
Last Updated
March 27, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing