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.

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). Approximately 946 participants will be enrolled and will be 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis, Primary Progressive
• Intervention / Treatment: Drug: Fenebrutinib; Drug: Placebo matched to ocrelizumab; Drug: Ocrelizumab; Drug: Placebo matched to fenebrutinib

• Study Type: Interventional
• Enrollment (Actual): 985
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: GN41791 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1424
    • Centro de Especialidades Neurológicas y Rehabilitación - CENyR
  • Caba, Argentina, C1126AAB
    • Instituto De Neurología Cognitiva - INECO
  • Ciudad Autonoma de Buenos Aires, Argentina, C1012AAR
    • Instituto de Investigaciones Metabolicas (IDIM)
  • Cordoba, Argentina, X5000EDC
    • Instituto Reumatológico Strusberg
  • Rosario, Argentina, S2000BZL
    • Fundacion Rosarina de Neurorehabilitacion
  • San Miguel, Argentina, T4000AXL
    • Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Brain and Mind Research Institute
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital; Department of Neurology
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital; Department of Neurology
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital; Department of Neurology
• Austria
  • Linz, Austria, 4020
    • Kepler Universitätsklinikum GmbH - Neuromed Campus; Neurologie
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik fuer Neurologie
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Santa Casa de Misericordia; de Belo Horizonte
  • PR
    • Curitiba, PR, Brazil, 81210-310
      • Instituto de Neurologia de Curitiba
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20270-004
      • Hospital Universitario Gaffree e Guinle
  • RS
    • Porto Alegre, RS, Brazil, 90110-000
      • IMV Pesquisa Neurológica
    • Porto Alegre, RS, Brazil, 90430-001
      • Núcleo de Pesquisa do Rio Grande do Sul
  • SC
    • Joinville, SC, Brazil, 89202-190
      • Clinica Neurologica; Neurocirurgica de Joinville
  • SP
    • Sao Paulo, SP, Brazil, 01228-200
      • Centro de Pesquisas Clinicas; CPCLIN
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases
  • Sofia, Bulgaria, 1113
    • Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z1
      • University of Alberta Hospital
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Fraser Health Authority - Fraser Health Multiple Sclerosis
    • Vancouver, British Columbia, Canada, V6T 1Z4
      • University of British Columbia
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Regional health authority A vitalite health network
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre Uni Campus
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5B-1W8
      • St. Michael's Hospital; MS Clinic
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 1W2
      • Clinique NeuroOutaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche Sepmus Inc.
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
• Chile
  • Santiago, Chile, 8331143
    • CECIM Biocinetic
  • Vitacura, Chile, 7650568
    • Clínica Alemana
• Colombia
  • Bogota, D.C., Colombia, 111321
    • Organizacion Sanitas Internacional
  • Cali, Colombia
    • Fundacion Clinica Valle del Lili; Unidad de Investigaciones Clinicas
  • Medellin, Colombia
    • Instituto Neurologico de Colombia INDEC
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken
  • Glostrup, Denmark, 2600
    • Rigshospitalet; Neurologisk Klinik Glostrup
• France
  • Bordeaux, France, 33076
    • Groupe Hospitalier Pellegrin; Service de neurochirurgie B
  • Bron, France, 69677
    • Hopital Pierre Wertheimer; Neurologie D
  • Montpellier, France, 34295
    • CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie
  • Nantes, France, 44805
    • Hopital Guillaume Et Rene Laennec
  • Nice, France, 06002
    • Hôpital Pasteur; Service de Neurologie
  • Strasbourg, France, 67091
    • Hopital Civil de Strasbourg; Service de Neurologie
• Germany
  • Berlin, Germany, 10117
    • Charite - Universitatsmedizin Berlin; Klinik fur Neurologie
  • Böblingen, Germany, 71034
    • Studienzentrum fur Neurologie und Psychiatrie
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
  • Tuebingen, Germany, 72076
    • Universitaetsklinikum Tuebingen; Abteilung Neurologie
  • Wiesbaden, Germany, 65191
    • Deutsche Klinik für Diagnostik; DKD Helios Klinik Wiesbaden, Abt. Neurologie
• Greece
  • Athens, Greece, 115 25
    • 401 Military Hospital of Athens; Neurology Department
  • Athens, Greece, 115 28
    • Hospital Eginition; First Department of Neurology
  • Thessaloniki, Greece, 546 36
    • AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.
• Hungary
  • Budapest, Hungary, 1033
    • Clinexpert Kft.
  • Budapest, Hungary, 1138
    • S-Medicon Egeszsegugyi Szolgaltato Kft.
  • Budapest, Hungary, 1204
    • Budapesti Jahn Ferenc Dél-pesti Kórház és Rendel?intézet
  • Eger, Hungary, 3300
    • Markhot Ferenc Oktatokorhaz és Rendelointezet; Neurologiai és Stroke Osztaly
  • Kistarcsa, Hungary, 2143
    • Pest Megyei Flor Ferenc Korhaz
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center; Neurology Unit
  • Ramat-Gan, Israel, 5262100
    • The Chaim Sheba Medical Center; Multiple Sclerosis Center
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center; Department of Neurology
• Italy
  • Campania
    • Napoli, Campania, Italy, 80138
      • AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica
  • Emilia-Romagna
    • Parma, Emilia-Romagna, Italy, 43126
      • A.O.U. di Parma; SC Neurologia, Amb. Sclerosi Multipla (malattie demielinizzanti)
  • Lazio
    • Roma, Lazio, Italy, 00133
      • Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Irccs A.O.U.San Martino Ist; Dinogmi
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
    • Montichiari, Lombardia, Italy, 25018
      • Ospedale Civile di Montichiari; Centro Sclerosi Multipla
  • Molise
    • Pozzilli, Molise, Italy, 86077
      • IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • A.R.N.A.S. Civico Di Cristina Benfratelli; U.O.C. Neurologia con Stroke Unit
• Mexico
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03100
      • Mexico Centre for Clinical Research
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03600
      • Grupo Medico Camino S.C.
    • Ciudad de México, Mexico CITY (federal District), Mexico, 07760
      • Hospital Juarez de Mexico
    • Mexico City, Mexico CITY (federal District), Mexico, 06700
      • Clinstile S.A de C.V.
    • Tlalnepantla de Baz, Mexico CITY (federal District), Mexico, 54055
      • Clinical Research Institute
• North Macedonia
  • Skopje, North Macedonia, 1000
    • University Clinic of Neurology; Movement Disorders
• Peru
  • Bellavista, Peru, Callao 2
    • Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion
  • Lima, Peru, 15001
    • Clinica Internacional; Unidad De Investigacion
  • Lima, Peru, Lima 01
    • Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo; Peru
• Poland
  • Bydgoszcz, Poland, 85-796
    • Neurocentrum Bydgoszcz sp. z o.o
  • Katowice, Poland, 40-568
    • Care Clinic
  • Lodz, Poland, 90-324
    • Centrum Neurologii Krzysztof Selmaj
  • Pozna?, Poland, 60-693
    • Med Polonia
  • Rzeszow, Poland, 35-055
    • Centrum Medyczne "Medyk"
  • Rzeszów, Poland, 35-232
    • Nmedis sp. z o.o.
  • Siemianowice ?l?skie, Poland, 41-100
    • Neuro-Care Sp. z o.o. Sp. Komandytowa
  • Warszawa, Poland, 01-684
    • Centrum Medyczne NeuroProtect
  • Wroc?aw, Poland, 51-685
    • Wro Medica
  • Zabrze, Poland, 41-800
    • SPSK nr 1; Klinika Neurologii
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga; Servico de Neurologia
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Neurologia
  • Lisboa, Portugal, 1169-050
    • Hospital Santo Antonio dos Capuchos; Servico de Neurologia
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio; Servico de Neurologia
  • Porto, Portugal, 4200-319
    • Hospital de Sao Joao; Servico de Neurologia
• Puerto Rico
  • Guaynabo, Puerto Rico, 00968
    • San Juan MS Center
• Russian Federation
  • Kirov, Russian Federation, 610007
    • Center of Cardiology and Neurology
  • Novosibirsk, Russian Federation, 630087
    • State Novosibirsk Regional Clinical Hospital
  • Krasnojarsk
    • Krasnoyarsk, Krasnojarsk, Russian Federation, 660037
      • FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
    • Krasnoyarsk, Krasnojarsk, Russian Federation, 660049
      • Krasnoyarsk State Medical Academy
  • Leningrad
    • Sankt-peterburg, Leningrad, Russian Federation, 197110
      • National Center of Social Significant Disease
  • Moskovskaja Oblast
    • Moskva, Moskovskaja Oblast, Russian Federation, 117997
      • Federal center of brain research and neurotechnologies
    • Moskva, Moskovskaja Oblast, Russian Federation, 127015
      • City Clinical Hospital #24; Multipal Sclerosis department
  • Sankt Petersburg
    • St. Petersburg, Sankt Petersburg, Russian Federation, 197706
      • City Hospital #40 of Resort Administrative District
  • Sverdlovsk
    • Yekaterinburg, Sverdlovsk, Russian Federation, 620102
      • Sverdlovsk Regional Clinical Hospital 1
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420047
      • Vertebronevrologiya LLC
  • Tjumen
    • Tyumen, Tjumen, Russian Federation, 625048
      • Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik; Neurology
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
  • Cadiz, Spain, 11009
    • Hospital Puerta del Mar; Sevicio de Neurologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Malaga ? Hospital General; Servicio de Neurologia
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • LA Coruña
    • Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia
  • Lerida
    • Lleida, Lerida, Spain, 25198
      • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Neurología
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Neurologia
  • Pontevedra
    • Vigo, Pontevedra, Spain
      • Hospital Alvaro Cunqueiro; Servicio de Neurologia
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel; Neurologie
  • Bern, Switzerland, 3010
    • Inselspital Bern Medizin Neurologie
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty; Neurology
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
  • Istanbul, Turkey, 42131
    • Selcuk University Medical Faculty; Norology department
  • Istanbul, Turkey, 34785
    • Sancaktepe Training and Research Hospital; Neurology
  • Kocaeli, Turkey, 41380
    • Kocaeli University Hospital; Department of Neurology
  • Mersin, Turkey, 33079
    • Mersin University Medical Faculty; Neurology
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Univ. Med. Fac.; Neurology
  • Trabzon, Turkey, 61080
    • Karadeniz Tecnical Uni. Med. Fac.; Neurology
  • Van, Turkey, 65080
    • Van Yuzuncu Yil University Hospital; Neurology
  • Çankaya, Turkey, 06490
    • Baskent Universitesi Ankara Hastanesi; Noroloji Bolumu
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital; Neurology Department
  • Kharkov, Ukraine, 61068
    • Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology
  • Lutsk, Ukraine, 43024
    • Volyn Regional Clinical Hospital
  • Odesa, Ukraine, 65117
    • Odesa Regional Clinical Hospital; Neurosurgery Department
  • Chernihiv Governorate
    • Chernivtsi, Chernihiv Governorate, Ukraine, 58022
      • CNPE City Clinical Hospital #3 of Chernivtsi City Council
    • Lviv, Chernihiv Governorate, Ukraine, 79007
      • MNE Lviv Territorial Medical Association Clinical Hospital for Palliative Care
  • Crimean Regional Governmenta
    • Zhytomir, Crimean Regional Governmenta, Ukraine, 10008
      • Medical Centre of PE First Private Clinic
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 03037
      • MEDBUD
    • Lviv, KIEV Governorate, Ukraine, 79010
      • Lviv Regional Clinical Hospital
    • Vinnytsia, KIEV Governorate, Ukraine, 21050
      • Salutem Medical Center
  • Kharkiv Governorate
    • Dnipro, Kharkiv Governorate, Ukraine, 49038
      • Separated structural unit ?University clinic? of Dnipro State Medical University
    • Kharkiv, Kharkiv Governorate, Ukraine, 61058
      • Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital
    • Zaporizhzhia, Kharkiv Governorate, Ukraine, 69600
      • Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council
  • Podolia Governorate
    • Vinnytsia, Podolia Governorate, Ukraine, 21009
      • Medical Clinical Research Center of Medical Center LLC Health Clinic
• United Kingdom
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospitals NHS Trust
  • Swansea, United Kingdom, SA6 6NL
    • Morriston Hospital
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Alabama Neurology Associates
  • California
    • Berkeley, California, United States, 94705
      • Sutter East Bay Medical Foundation
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation Research Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • Uni of Miami School of Medicine
    • Orlando, Florida, United States, 32806
      • Neurological Services of Orlando
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology PC
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University School Of Medicine; Outpatient Center
  • Massachusetts
    • Wellesley, Massachusetts, United States, 02481
      • Dragonfly Research, LLC
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Washington University
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo; Center for Brain Research
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack U Med Ctr
    • Livingston, New Jersey, United States, 07039
      • Barnabas Health Ambulatory Care Center
    • Neptune, New Jersey, United States, 07753
      • Jersey Shore University Medical Centre
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital; Institute For Clinical Research
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurological Institute
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Medical Center
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health Neurosciences Institute ? Charlotte
    • Hickory, North Carolina, United States, 28602
      • Neurology Associates PA
    • Raleigh, North Carolina, United States, 27607-6520
      • Raleigh Neurology Associates
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South; Dayton Physician's Office
    • Cincinnati, Ohio, United States, 45219
      • UC Health, LLC.
    • Columbus, Ohio, United States, 43214
      • OhioHealth Riverside Methodist Hospital; Pharmacy Services
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Brain and Spine Institute
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
    • Knoxville, Tennessee, United States, 37922
      • Hope Neurology
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Uni of Texas Health Science Center At Houston
    • Sherman, Texas, United States, 75092
      • Texas Institute for Neurological Disorders
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen MS Center
    • Seattle, Washington, United States, 98104-1360
      • Swedish Medical Center
  • West Virginia
    • Charleston, West Virginia, United States, 25304
      • West Virginia University
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226-3596
      • Medical College of Wisconsin, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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)
• 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.
• Immunocompromised state, history of primary or secondary (non-drug related) immunodeficiency, or history of transplantation or antirejection therapy
• Known bleeding diathesis, anemia, or history of hospitalization or transfusion for gastrointestinal (GI) bleed
• Any previous treatment with cladribine, mitoxantrone, daclizumab, alemtuzumab, or cyclophosphamide

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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fenebrutinib; Participants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.	Drug: Fenebrutinib; Participants will receive fenebrutinib.; Drug: Placebo matched to ocrelizumab; Participants will receive ocrelizumab-matching placebo.
Active Comparator: Ocrelizumab; Participants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.	Drug: Ocrelizumab; Participants will receive ocrelizumab.; Drug: Placebo matched to fenebrutinib; Participants will receive fenebrutinib-matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)	Minimum of 120 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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, 96, 108 and 120
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, 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 120 weeks
Percentage of Participants with Adverse Events (AEs)		Up to 4.7 years
Plasma Concentrations of Fenebrutinib at Specified Timepoints		Up to 4.7 years
Percent Change from Screening in Serum Neurofilament Light Chain (NfL) Levels		Up to Week 120

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2020
• Primary Completion (Estimated): January 16, 2026
• Study Completion (Estimated): December 18, 2026

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: September 4, 2020
• First Posted (Actual): September 10, 2020

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: GN41791; 2019-003919-53 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No