A Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Ocrelizumab in Adult Participants With Primary Progressive Multiple Sclerosis

Multiple Sclerosis, Primary Progressive Clinical Trial

— FENtrepid  

Official title:

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04544449
• Other study ID #: GN41791
• Secondary ID: 2019-003919-53
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 26, 2020
• Est. completion date: December 18, 2026

Study information

• Verified date: February 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 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 985
• Est. completion date: December 18, 2026
• Est. primary completion date: January 16, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Primary Progressive
• Sclerosis

Intervention

Drug:
• Fenebrutinib
Participants will receive fenebrutinib.
• Ocrelizumab
Participants will receive ocrelizumab.
• Placebo matched to ocrelizumab
Participants will receive ocrelizumab-matching placebo.
• Placebo matched to fenebrutinib
Participants will receive fenebrutinib-matching placebo

Locations

Country	Name	City	State
Argentina	Centro de Especialidades Neurológicas y Rehabilitación - CENyR	Buenos Aires
Argentina	Instituto De Neurología Cognitiva - INECO	Caba
Argentina	Instituto de Investigaciones Metabolicas (Idim)	Ciudad Autonoma de Buenos Aires
Argentina	Instituto Reumatológico Strusberg	Cordoba
Argentina	Fundacion Rosarina de Neurorehabilitacion	Rosario
Argentina	Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY	San Miguel
Australia	Box Hill Hospital; Department of Neurology	Box Hill	Victoria
Australia	Brain and Mind Research Institute	Camperdown	New South Wales
Australia	Austin Hospital; Department of Neurology	Heidelberg	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal Melbourne Hospital; Department of Neurology	Parkville	Victoria
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Kepler Universitätsklinikum GmbH - Neuromed Campus; Neurologie	Linz
Austria	Medizinische Universität Wien; Univ.Klinik fuer Neurologie	Wien
Brazil	Santa Casa de Misericordia; de Belo Horizonte	Belo Horizonte	MG
Brazil	Instituto de Neurologia de Curitiba	Curitiba	PR
Brazil	Clinica Neurologica; Neurocirurgica de Joinville	Joinville	SC
Brazil	IMV Pesquisa Neurológica	Porto Alegre	RS
Brazil	Núcleo de Pesquisa do Rio Grande do Sul	Porto Alegre	RS
Brazil	Hospital Universitario Gaffree e Guinle	Rio de Janeiro	RJ
Brazil	Centro de Pesquisas Clinicas; CPCLIN	Sao Paulo	SP
Bulgaria	UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases	Pleven
Bulgaria	Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD	Sofia
Canada	Fraser Health Authority - Fraser Health Multiple Sclerosis	Burnaby	British Columbia
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Clinique NeuroOutaouais	Gatineau	Quebec
Canada	Recherche Sepmus Inc.	Greenfield Park	Quebec
Canada	London Health Sciences Centre Uni Campus	London	Ontario
Canada	Regional health authority A vitalite health network	Moncton	New Brunswick
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis	Ottawa	Ontario
Canada	St. Michael's Hospital; MS Clinic	Toronto	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Chile	CeCim Biocinetic	Santiago
Chile	Clinica Alemana	Vitacura
Colombia	Organizacion Sanitas Internacional	Bogota, D.C.
Colombia	Fundacion Clinica Valle del Lili; Unidad de Investigaciones Clinicas	Cali
Colombia	Instituto Neurologico de Colombia INDEC	Medellin
Denmark	Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken	Aarhus N
Denmark	Rigshospitalet; Neurologisk Klinik Glostrup	Glostrup
France	Groupe Hospitalier Pellegrin; Service de neurochirurgie B	Bordeaux
France	Hopital Pierre Wertheimer; Neurologie D	Bron
France	CHRU de Montpellier, Hopital Gui de Chauliac; Service de Neuropediatrie	Montpellier
France	Hopital Guillaume Et Rene Laennec	Nantes
France	Hôpital Pasteur; Service de Neurologie	Nice
France	Hopital Civil de Strasbourg; Service de Neurologie	Strasbourg
Germany	Charite - Universitatsmedizin Berlin; Klinik fur Neurologie	Berlin
Germany	Studienzentrum für Neurologie und Psychiatrie	Böblingen
Germany	Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften	Dresden
Germany	Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie	Freiburg
Germany	Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum	München
Germany	Universitaetsklinikum Tuebingen; Abteilung Neurologie	Tuebingen
Germany	Deutsche Klinik für Diagnostik; DKD Helios Klinik Wiesbaden, Abt. Neurologie	Wiesbaden
Greece	401 Military Hospital of Athens; Neurology Department	Athens
Greece	Hospital Eginition; First Department of Neurology	Athens
Greece	AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.	Thessaloniki
Hungary	Budapesti Jahn Ferenc Dél-pesti Kórház és Rendel?intézet	Budapest
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
Israel	Rambam Medical Center; Neurology Unit	Haifa
Israel	The Chaim Sheba Medical Center; Multiple Sclerosis Center	Ramat-Gan
Israel	Tel Aviv Sourasky Medical Center; Department of Neurology	Tel Aviv
Italy	Irccs A.O.U.San Martino Ist; Dinogmi	Genova	Liguria
Italy	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia
Italy	Ospedale Civile di Montichiari; Centro Sclerosi Multipla	Montichiari	Lombardia
Italy	AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica	Napoli	Campania
Italy	A.R.N.A.S. Civico Di Cristina Benfratelli; U.O.C. Neurologia con Stroke Unit	Palermo	Sicilia
Italy	A.O.U. di Parma; SC Neurologia, Amb. Sclerosi Multipla (malattie demielinizzanti)	Parma	Emilia-Romagna
Italy	IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla	Pozzilli	Molise
Italy	Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla	Roma	Lazio
Mexico	Grupo Médico Camino S.C.	Ciudad de México	Mexico CITY (federal District)
Mexico	Hospital Juarez de Mexico	Ciudad de México	Mexico CITY (federal District)
Mexico	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	Clinical Research Institute	Tlalnepantla de Baz	Mexico CITY (federal District)
North Macedonia	University Clinic of Neurology; Movement Disorders	Skopje
Peru	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista
Peru	Clinica Internacional; Unidad De Investigacion	Lima
Peru	Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo; Peru	Lima
Poland	Neurocentrum Bydgoszcz sp. z o.o	Bydgoszcz
Poland	Care Clinic	Katowice
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	Med Polonia	Pozna?
Poland	Centrum Medyczne "MEDYK"	Rzeszow
Poland	Nmedis sp. z o.o.	Rzeszów
Poland	NEURO-CARE Sp. z o.o. Sp. Komandytowa	Siemianowice ?l?skie
Poland	Centrum Medyczne NeuroProtect	Warszawa
Poland	Wro Medica	Wroc?aw
Poland	SPSK nr 1; Klinika Neurologii	Zabrze
Portugal	Hospital de Braga; Servico de Neurologia	Braga
Portugal	Hospital de Santa Maria; Servico de 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
Puerto Rico	San Juan MS Center	Guaynabo
Russian Federation	Vertebronevrologiya LLC	Kazan	Tatarstan
Russian Federation	Center of Cardiology and Neurology	Kirov
Russian Federation	FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency	Krasnoyarsk	Krasnojarsk
Russian Federation	Krasnoyarsk State Medical Academy	Krasnoyarsk	Krasnojarsk
Russian Federation	City Clinical Hospital #24; Multipal Sclerosis department	Moskva	Moskovskaja Oblast
Russian Federation	Federal center of brain research and neurotechnologies	Moskva	Moskovskaja Oblast
Russian Federation	State Novosibirsk Regional Clinical Hospital	Novosibirsk
Russian Federation	National Center of Social Significant Disease	Sankt-peterburg	Leningrad
Russian Federation	City Hospital #40 of Resort Administrative District	St. Petersburg	Sankt Petersburg
Russian Federation	Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik; Neurology	Tyumen	Tjumen
Russian Federation	Sverdlovsk Regional Clinical Hospital 1	Yekaterinburg	Sverdlovsk
Spain	Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia	Barcelona
Spain	Hospital Puerta del Mar; Sevicio de Neurologia	Cadiz
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia	Coruña	LA Coruña
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Neurología	Lleida	Lerida
Spain	Hospital Ramon y Cajal; 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	Universitätsspital Basel; Neurologie	Basel
Switzerland	Inselspital Bern Medizin Neurologie	Bern
Turkey	Hacettepe University Medical Faculty; Neurology	Ankara
Turkey	Baskent Universitesi Ankara Hastanesi; Noroloji Bolumu	Çankaya
Turkey	Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali	Istanbul
Turkey	Sancaktepe Training and Research Hospital; Neurology	Istanbul
Turkey	Selcuk University Medical Faculty; Norology department	Istanbul
Turkey	Kocaeli University Hospital; Department of Neurology	Kocaeli
Turkey	Mersin University Medical Faculty; Neurology	Mersin
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
Turkey	Karadeniz Tecnical Uni. Med. Fac.; Neurology	Trabzon
Turkey	Van Yuzuncu Yil University Hospital; Neurology	Van
Ukraine	CNPE City Clinical Hospital #3 of Chernivtsi City Council	Chernivtsi	Chernihiv Governorate
Ukraine	Separated structural unit ?University clinic? of Dnipro State Medical University	Dnipro	Kharkiv Governorate
Ukraine	Regional Clinical Hospital; Neurology Department	Ivano-Frankivsk
Ukraine	Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital	Kharkiv	Kharkiv Governorate
Ukraine	Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology	Kharkov
Ukraine	MEDBUD	Kyiv	KIEV Governorate
Ukraine	Volyn Regional Clinical Hospital	Lutsk
Ukraine	Lviv Regional Clinical Hospital	Lviv	KIEV Governorate
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 Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council	Zaporizhzhia	Kharkiv Governorate
Ukraine	Medical Centre of PE First Private Clinic	Zhytomir	Crimean Regional Governmenta
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Charing Cross Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Morriston Hospital	Swansea
United States	Dent Neurological Institute	Amherst	New York
United States	University of Colorado Denver	Aurora	Colorado
United States	Johns Hopkins University School Of Medicine; Outpatient Center	Baltimore	Maryland
United States	Sutter East Bay Medical Foundation	Berkeley	California
United States	Miami Valley Hospital South; Dayton Physician's Office	Centerville	Ohio
United States	West Virginia University	Charleston	West Virginia
United States	Atrium Health Neurosciences Institute ? Charlotte	Charlotte	North Carolina
United States	UC Health, LLC.	Cincinnati	Ohio
United States	OhioHealth Riverside Methodist Hospital; Pharmacy Services	Columbus	Ohio
United States	Neurology Clinic PC	Cordova	Tennessee
United States	Wayne State University	Detroit	Michigan
United States	Fullerton Neurology and Headache Center	Fullerton	California
United States	Minneapolis Clinic of Neurology	Golden Valley	Minnesota
United States	Hackensack U Med Ctr	Hackensack	New Jersey
United States	Neurology Associates PA	Hickory	North Carolina
United States	Alabama Neurology Associates	Homewood	Alabama
United States	Uni of Texas Health Science Center At Houston	Houston	Texas
United States	Josephson Wallack Munshower Neurology PC	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Evergreen MS Center	Kirkland	Washington
United States	Hope Neurology	Knoxville	Tennessee
United States	Cleveland Clinic Lou Ruvo; Center for Brain Research	Las Vegas	Nevada
United States	Barnabas Health Ambulatory Care Center	Livingston	New Jersey
United States	Uni of Miami School of Medicine	Miami	Florida
United States	Medical College of Wisconsin, Inc.	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Jersey Shore University Medical Centre	Neptune	New Jersey
United States	Yale University School Of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Neurological Services of Orlando	Orlando	Florida
United States	Providence Brain and Spine Institute	Portland	Oregon
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	University of Rochester	Rochester	New York
United States	Washington University	Saint Louis	Missouri
United States	Swedish Medical Center	Seattle	Washington
United States	Texas Institute for Neurological Disorders	Sherman	Texas
United States	Stony Brook University Medical Center	Stony Brook	New York
United States	Palo Alto Medical Foundation Research Center	Sunnyvale	California
United States	SUNY Upstate Medical University	Syracuse	New York
United States	University of South Florida	Tampa	Florida
United States	Holy Name Hospital; Institute For Clinical Research	Teaneck	New Jersey
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Dragonfly Research, LLC	Wellesley	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Brazil,  Bulgaria,  Canada,  Chile,  Colombia,  Denmark,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Mexico,  North Macedonia,  Peru,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)		Minimum of 120 weeks
Secondary	Time to Onset of Composite 24-week CDP (cCDP24)		Minimum of 120 weeks
Secondary	Time to Onset of 12-week CDP (CDP12)		Minimum of 120 weeks
Secondary	Time to Onset of 24-week CDP (CDP24)		Minimum of 120 weeks
Secondary	Percentage Change in Total Brain Volume Assessed by Magnetic Resonance Imaging (MRI)		From Week 24 to Week 120
Secondary	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
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, 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
Secondary	Percentage of Participants with Adverse Events (AEs)		Up to 4.7 years
Secondary	Plasma Concentrations of Fenebrutinib at Specified Timepoints		Up to 4.7 years
Secondary	Percent Change from Screening in Serum Neurofilament Light Chain (NfL) Levels		Up to Week 120