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

NCT ID: NCT04544449

Last Updated: 2025-12-24

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 985 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-26
• Study Completion Date: 2027-07-21

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.

Conditions

Multiple Sclerosis, Primary Progressive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Fenebrutinib

Participants will receive oral fenebrutinib and intravenous (IV) ocrelizumab-matching placebo.

Group Type: EXPERIMENTAL

Fenebrutinib

Intervention Type: DRUG

Participants will receive fenebrutinib.

Placebo matched to ocrelizumab

Intervention Type: DRUG

Participants will receive ocrelizumab-matching placebo.

Ocrelizumab

Participants will receive intravenous (IV) ocrelizumab and oral fenebrutinib-matching placebo.

Group Type: ACTIVE_COMPARATOR

Ocrelizumab

Intervention Type: DRUG

Participants will receive ocrelizumab.

Placebo matched to fenebrutinib

Intervention Type: DRUG

Participants will receive fenebrutinib-matching placebo

Interventions

Fenebrutinib

Participants will receive fenebrutinib.

Intervention Type: DRUG

Ocrelizumab

Participants will receive ocrelizumab.

Intervention Type: DRUG

Placebo matched to ocrelizumab

Participants will receive ocrelizumab-matching placebo.

Intervention Type: DRUG

Placebo matched to fenebrutinib

Participants will receive fenebrutinib-matching placebo

Intervention Type: DRUG

Eligibility Criteria

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.

• 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.

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)
• 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.
• 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

• Chronic liver disease unless considered stable for > 6 months
• Acute liver disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Alabama Neurology Associates

Homewood, Alabama, United States

Sutter East Bay Medical Foundation

Berkeley, California, United States

Fullerton Neurology and Headache Center

Fullerton, California, United States

Palo Alto Medical Foundation Research Center

Sunnyvale, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Yale University School Of Medicine

Fairfield, Connecticut, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Neurology Associates PA

Maitland, Florida, United States

Neurological Services of Orlando

Orlando, Florida, United States

University of South Florida

Tampa, Florida, United States

Josephson Wallack Munshower Neurology PC

Indianapolis, Indiana, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins University School Of Medicine

Baltimore, Maryland, United States

Dragonfly Research, LLC

Wellesley, Massachusetts, United States

Wayne State University

Detroit, Michigan, United States

Minneapolis Clinic of Neurology

Golden Valley, Minnesota, United States

Washington University

St Louis, Missouri, United States

Cleveland Clinic Lou Ruvo

Las Vegas, Nevada, United States

Hackensack U Med Ctr

Hackensack, New Jersey, United States

Barnabas Health Ambulatory Care Center

Livingston, New Jersey, United States

Jersey Shore University Medical Centre

Neptune City, New Jersey, United States

Rutgers New Jersey Medical School

Newark, New Jersey, United States

Holy Name Hospital

Teaneck, New Jersey, United States

Dent Neurological Institute

Amherst, New York, United States

Columbia University Medical Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Atrium Health Neurosciences Institute ? Charlotte

Charlotte, North Carolina, United States

Raleigh Neurology Associates

Raleigh, North Carolina, United States

Miami Valley Hospital South

Centerville, Ohio, United States

UC Health, LLC.

Cincinnati, Ohio, United States

OhioHealth Riverside Methodist Hospital

Columbus, Ohio, United States

Providence Brain and Spine Institute

Portland, Oregon, United States

Neurology Clinic PC

Cordova, Tennessee, United States

Hope Neurology

Knoxville, Tennessee, United States

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Uni of Texas Health Science Center At Houston

Houston, Texas, United States

Texas Institute for Neurological Disorders

Sherman, Texas, United States

Evergreen MS Center

Kirkland, Washington, United States

Swedish Medical Center

Seattle, Washington, United States

West Virginia University

Morgantown, West Virginia, United States

Medical College of Wisconsin, Inc.

Milwaukee, Wisconsin, United States

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

Buenos Aires, , Argentina

Focus CECIC

Buenos Aires, , Argentina

Instituto Reumatológico Strusberg

Córdoba, , Argentina

Fundacion Rosarina de Neurorehabilitacion

Rosario, , Argentina

Centro de Investigaciones Médicas Tucuman

San Miguel, , Argentina

Brain and Mind Research Institute

Camperdown, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

John Hunter Hospital

New Lambton, New South Wales, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

Kepler Universitätsklinikum GmbH - Neuromed Campus

Linz, , Austria

Medizinische Universität Wien

Vienna, , Austria

Santa Casa de Misericordia

Belo Horizonte, Minas Gerais, Brazil

Instituto de Neurologia de Curitiba

Curitiba, Paraná, Brazil

Núcleo de Pesquisa do Rio Grande do Sul

Porto Alegre, Rio Grande do Sul, Brazil

IMV Pesquisa Neurológica

Porto Alegre, Rio Grande do Sul, Brazil

Clinica Neurologica

Joinville, Santa Catarina, Brazil

Centro de Pesquisas Clinicas

São Paulo, São Paulo, Brazil

Hospital Universitario Gaffree e Guinle

Rio de Janeiro, , Brazil

UMHAT Dr. Georgi Stranski

Pleven, , Bulgaria

Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD

Sofia, , Bulgaria

University of Alberta Hospital

Edmonton, Alberta, Canada

Fraser Health Authority - Fraser Health Multiple Sclerosis

Burnaby, British Columbia, Canada

University of British Columbia

Vancouver, British Columbia, Canada

London Health Sciences Centre Uni Campus

London, Ontario, Canada

The Ottawa Hospital - General Campus

Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Clinique NeuroOutaouais

Gatineau, Quebec, Canada

Recherche Sepmus Inc.

Greenfield Park, Quebec, Canada

Montreal Neurological Institute and Hospital

Montreal, Quebec, Canada

CeCim Biocinetic

Santiago, , Chile

Clinica Alemana

Vitacura, , Chile

Organizacion Sanitas Internacional

Bogotá, , Colombia

Fundacion Clinica Valle del Lili

Cali, , Colombia

Instituto Neurologico de Colombia INDEC

Medellín, , Colombia

Aarhus Universitetshospital

Aarhus N, , Denmark

Rigshospitalet

Glostrup Municipality, , Denmark

Groupe Hospitalier Pellegrin

Bordeaux, , France

Hopital Pierre Wertheimer

Bron, , France

CHRU de Montpellier, Hopital Gui de Chauliac

Montpellier, , France

Hopital Guillaume Et Rene Laennec

Nantes, , France

Hôpital Pasteur

Nice, , France

Hopitaux Universitaires de Strasbourg

Strasbourg, , France

Charite - Universitatsmedizin Berlin

Berlin, , Germany

Studienzentrum Dr. Bischof GmbH

Böblingen, , Germany

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

Dresden, , Germany

Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie

Freiburg im Breisgau, , Germany

Klinikum rechts der Isar der TU Muenchen

München, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Deutsche Klinik für Diagnostik

Wiesbaden, , Germany

Hospital Eginition

Athens, , Greece

401 Military Hospital of Athens

Athens, , Greece

AHEPA Univ. General Hospital of Thessaloniki

Thessaloniki, , Greece

Clinexpert Kft.

Budapest, , Hungary

S-Medicon Egeszsegugyi Szolgaltato Kft.

Budapest, , Hungary

Budapesti Jahn Ferenc Dél-pesti Kórház és Rendel?intézet

Budapest, , Hungary

Markhot Ferenc Oktatokorhaz és Rendelointezet

Eger, , Hungary

Pest Megyei Flor Ferenc Korhaz

Kistarcsa, , Hungary

Rambam Medical Center

Haifa, , Israel

The Chaim Sheba Medical Center

Ramat Gan, , Israel

Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

AOU Seconda Università degli Studi

Napoli, Campania, Italy

A.O.U. di Parma

Parma, Emilia-Romagna, Italy

Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla

Rome, Lazio, Italy

Irccs A.O.U.San Martino Ist

Genoa, Liguria, Italy

IRCCS Ospedale San Raffaele

Milan, Lombardy, Italy

Ospedale Civile di Montichiari

Montichiari, Lombardy, Italy

IRCCS Istituto Neurologico Neuromed

Pozzilli, Molise, Italy

A.R.N.A.S. Civico Di Cristina Benfratelli

Palermo, Sicily, Italy

Mexico Centre for Clinical Research

Mexico City, Mexico CITY (federal District), Mexico

Clinstile S.A de C.V.

Mexico City, Mexico CITY (federal District), Mexico

Hospital Juarez de Mexico

Mexico City, Mexico CITY (federal District), Mexico

Grupo Médico Camino S.C.

México, Mexico CITY (federal District), Mexico

Clinical Research Institute

Tialnepantla, Mexico, Mexico

University Clinic of Neurology

Skopje, , North Macedonia

Hospital IV Alberto Sabogal Sologuren

Bellavista, , Peru

Clinica Internacional

Lima, , Peru

Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo

Lima, , Peru

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, , Poland

Care Clinic

Katowice, , Poland

NEURO-CARE Sp. z o.o. Sp. Komandytowa

Katowice, , Poland

Centrum Neurologii Krzysztof Selmaj

Lodz, , Poland

Med Polonia

Późna, , Poland

Centrum Medyczne "MEDYK"

Rzeszów, , Poland

Nmedis sp. z o.o.

Rzeszów, , Poland

Centrum Medyczne NeuroProtect

Warsaw, , Poland

Wro Medica

Wroclaw, , Poland

SPSK nr 1

Zabrze, , Poland

Hospital de Braga

Braga, , Portugal

Hospital Santo Antonio dos Capuchos

Lisbon, , Portugal

Hospital de Santa Maria

Lisbon, , Portugal

Hospital Geral de Santo Antonio

Porto, , Portugal

Hospital de Sao Joao

Porto, , Portugal

San Juan MS Center

Guaynabo, , Puerto Rico

Krasnoyarsk State Medical Academy

Krasnoyarsk, Krasnoyarsk Krai, Russia

FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

Krasnoyarsk, Krasnoyarsk Krai, Russia

Federal center of brain research and neurotechnologies

Moskva, Moscow Oblast, Russia

City Clinical Hospital #24

Moskva, Moscow Oblast, Russia

National Center of Social Significant Disease

Saint Petersburg, Sankt-Peterburg, Russia

City Hospital #40 of Resort Administrative District

Saint Petersburg, Sankt-Peterburg, Russia

Sverdlovsk Regional Clinical Hospital 1

Yekaterinburg, Sverdlovsk Oblast, Russia

Vertebronevrologiya LLC

Kazan', Tatarstan Republic, Russia

Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik

Tyumen, Tyumen Oblast, Russia

Center of Cardiology and Neurology

Kirov, , Russia

State Novosibirsk Regional Clinical Hospital

Novosibirsk, , Russia

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, LA Coruna, Spain

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, Lerida, Spain

Hospital Quiron de Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Puerta del Mar

Cadiz, , Spain

Hospital Ramon y Cajal

Madrid, , Spain

Hospital Regional Universitario de Malaga ? Hospital General

Málaga, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Universitätsspital Basel

Basel, , Switzerland

Inselspital Bern Medizin Neurologie

Bern, , Switzerland

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Baskent Universitesi Ankara Hastanesi

Çankaya, , Turkey (Türkiye)

Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi

Istanbul, , Turkey (Türkiye)

Sancaktepe Training and Research Hospital

Istanbul, , Turkey (Türkiye)

Selcuk University Medical Faculty

Istanbul, , Turkey (Türkiye)

Kocaeli University Hospital

Kocaeli, , Turkey (Türkiye)

Mersin University Medical Faculty

Mersin, , Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.

Samsun, , Turkey (Türkiye)

Karadeniz Tecnical Uni. Med. Fac.

Trabzon, , Turkey (Türkiye)

Van Yuzuncu Yil University Hospital

Van, , Turkey (Türkiye)

CNPE City Clinical Hospital #3 of Chernivtsi City Council

Chernivtsi, Chernihiv Governorate, Ukraine

MNE Lviv Territorial Medical Association Clinical Hospital for Palliative Care

Lviv, Chernihiv Governorate, Ukraine

Medical Centre of PE First Private Clinic

Zhytomyr, Crimean Regional Governmenta, Ukraine

Ams of Ukraine

Kharkiv, Kharkiv Governorate, Ukraine

Municipal Institution Zaporizhzhia Regional Clinical Hospital of Zaporizhzhia Regional Council

Zaporizhzhia, Kharkiv Governorate, Ukraine

MEDBUD

Kyiv, KIEV Governorate, Ukraine

Lviv Regional Clinical Hospital

Lviv, KIEV Governorate, Ukraine

Salutem Medical Center

Vinnytsia, KIEV Governorate, Ukraine

Separated structural unit ?University hospital? of Dnipro State Medical University

Dnipro, Tavria Okruha, Ukraine

Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

Volyn Regional Clinical Hospital

Lutsk, , Ukraine

Odesa Regional Clinical Hospital

Odesa, , Ukraine

Medical Clinical Research Center of Medical Center LLC Health Clinic

Vinnytsia, , Ukraine

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 Kingdom

Countries

Belgium; Czechia; India; New Zealand; 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; Russia; Spain; Switzerland; Turkey (Türkiye); Ukraine; United Kingdom

Other Identifiers

2019-003919-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2022-502611-10-00

Identifier Type: CTIS

Identifier Source: secondary_id

GN41791

Identifier Type: -

Identifier Source: org_study_id