A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)

NCT ID: NCT04548999

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 769 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-03
• Study Completion Date: 2027-09-08

Brief Summary

This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with PPMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.

Detailed Description

Participants will be treated for a minimum of 120 weeks in the double-blind treatment (DBT) phase. Upon positive primary results after the DBT phase, an optional higher dose extension treatment, open-label extension (OLE) phase is planned for eligible participants. The OLE will be carried out for approximately 96 weeks. Participants will be followed for safety for 48 weeks thereafter. Participants whose B-cell levels still did not replete to their baseline level or the lower limit of normal (LLN), whichever is lower, will move into the B-cell monitoring (BCM) phase following the safety follow-up phase. The study will end when all participants who were not treated with an alternative B-cell depleting therapy have repleted their B-cells to the baseline value or the LLN.

Conditions

Multiple Sclerosis

Study Design

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

Study Groups

Ocrelizumab Higher Dose

Participants will be randomized to receive a minimum of 5 higher treatment doses based on their body weight at baseline: 1200 mg (participant's body weight \<75 kilograms \[kg\]) or 1800 mg (participant's body weight ≥ 75 kg) of ocrelizumab administered by IV infusion Q24W in the DBT phase. During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.

Group Type: EXPERIMENTAL

Ocrelizumab

Intervention Type: DRUG

The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight <75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W.

During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total)

Antihistamine

Intervention Type: DRUG

Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

Methylprednisolone

Intervention Type: DRUG

Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Ocrelizumab Approved Dose

Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by IV infusion Q24W in the DBT phase. During the optional OLE phase, participants will be offered a higher dose of ocrelizumab (either 1200 or 1800 mg), based on their body weight at OLE baseline, for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.

Group Type: ACTIVE_COMPARATOR

Ocrelizumab

Intervention Type: DRUG

Ocrelizumab will be administered at a dose of 600 mg Q24W. The first dose of ocrelizumab will be administered as two 300 mg, IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion Q24W.

Antihistamine

Intervention Type: DRUG

Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

Methylprednisolone

Intervention Type: DRUG

Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Interventions

Ocrelizumab

The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight <75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W.

During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total)

Intervention Type: DRUG

Ocrelizumab

Ocrelizumab will be administered at a dose of 600 mg Q24W. The first dose of ocrelizumab will be administered as two 300 mg, IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion Q24W.

Intervention Type: DRUG

Antihistamine

Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

Intervention Type: DRUG

Methylprednisolone

Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Intervention Type: DRUG

Other Intervention Names

Ocrevus; Ocrevus; Non-Investigational Medicinal Product; Non-Investigational Medicinal Product

Eligibility Criteria

Inclusion Criteria

• Diagnosis of PPMS
• EDSS score at screening and baseline, from 3 to 6.5 inclusive
• Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
• Average 9HPT score over four trials (two trials with each hand) at screening and over four trials (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds
• Score of ≥ to 2.0 on the Functional Systems (FS) scale for the pyramidal system that was due to lower extremity findings at screening and baseline
• Documented magnetic resonance imaging (MRI) of brain with abnormalities consistent with MS
• Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization
• Participants must be neurologically stable for at least 30 days prior to randomization and baseline
• Disease duration from the onset of MS symptoms; if EDSS score at screening is ≤ 5, disease duration must be less than 10 years; If EDSS score at screening is > 5, disease duration must be less than 15 years
• Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands
• Females of childbearing potential: agreement to remain abstinent or use adequate contraceptive methods
• Female participants, without reproductive potential may be enrolled e.g. if post-menopausal or if surgically sterile

Exclusion Criteria

• History of relapsing remitting or secondary progressive MS at screening
• Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening
• History of confirmed or suspected progressive multifocal leukoencephalopathy
• History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
• Immunocompromised state
• Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
• Inability to complete an MRI or contraindication to gadolinium administration
• Contraindications to mandatory pre-medications for infusion-related reaction (IRRs)
• Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• Significant, uncontrolled disease that may preclude participant from participating in the study
• History of or currently active primary or secondary, non-drug-related, immunodeficiency
• Pregnant or breastfeeding or intending to become pregnant
• Lack of peripheral venous access
• History of alcohol or other drug abuse within 12 months prior to screening
• Treatment with any investigational agent or treatment with any experimental procedure for MS
• Previous use of anti-cluster of differentiation 20 (CD20s) (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy
• Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab
• Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
• Previous treatment with natalizumab within 4.5 months of baseline
• Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
• Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication
• Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
• Any previous history of transplantation or anti-rejection therapy
• Treatment with IV immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization
• Systemic corticosteroid therapy within 4 weeks prior to screening
• Positive screening tests for active, latent, or inadequately treated hepatitis B
• Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
• Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 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

21st Century Neurology

Phoenix, Arizona, United States

University of California Irvine

Irvine, California, United States

Stanford University Medical Center

Stanford, California, United States

University of Colorado Denver

Aurora, Colorado, United States

Advanced Neurosciences Research LLC

Fort Collins, Colorado, United States

MS and Neuromuscular Center of Excellence

Clearwater, Florida, United States

University of South Florida

Tampa, Florida, United States

Baptist Health Lexington

Nicholasville, Kentucky, United States

International Neurorehabilitation Institute

Lutherville, Maryland, United States

Massachusetts General Hospital.

Boston, Massachusetts, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

Michigan Institute for Neurological Disorders

Farmington Hills, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Jersey Shore University Medical Centre

Neptune City, New Jersey, United States

Northwell Health

Great Neck, New York, United States

Lenox Hill Hospital

New York, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

Neurology Clinic PC

Cordova, Tennessee, United States

Advanced Neurosciences Institute

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Lone Star Neurology of San Antonio

San Antonio, Texas, United States

Texas Institute for Neurological Disorders

Sherman, Texas, United States

Wheaton Franciscan Healthcare - St. Francis Outpatient Center

Milwaukee, Wisconsin, United States

CEMIC Saavedra

Buenos Aires, , Argentina

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

Buenos Aires, , Argentina

INECO

Rosario, , Argentina

Revalidatie en MS Centrum

Overpelt, , Belgium

L2 Ip Instituto de Pesquisas Clinicas Ltda ME

Brasília, Federal District, Brazil

Hospital das Clinicas - UFG

Goiânia, Goiás, Brazil

Instituto de Neurologia de Curitiba

Curitiba, Paraná, Brazil

Instituto Méderi de Pesquisa e Saúde

Passo Fundo, Rio Grande do Sul, Brazil

Hospital Moinhos de Vento

Porto Alegre, Rio Grande do Sul, Brazil

IMV Pesquisa Neurológica

Porto Alegre, Rio Grande do Sul, Brazil

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Clinica Neurologica

Joinville, Santa Catarina, Brazil

Hospital das Clinicas - UNICAMP

Campinas, São Paulo, Brazil

Praxis Pesquisa Médica

Santo André, São Paulo, Brazil

CPQuali Pesquisa Clinica Ltda

São Paulo, São Paulo, Brazil

UMHAT Dr. Georgi Stranski

Pleven, , Bulgaria

MHATNP Sveti Naum EAD

Sofia, , Bulgaria

Centre de Recherche Saint-Louis

Lévis, Quebec, Canada

Chum Campus Notre Dame

Montreal, Quebec, Canada

MUCH - Montreal Neurological Institute & Hospital

Montreal, Quebec, Canada

Aalborg Universitetshospital

Aalborg, , Denmark

Rigshospitalet Glostrup

Glostrup Municipality, , Denmark

CHU de Besancon Hopital Jean Minjoz

Besançon, , France

CHU Brest Hopital La Cavale Blanche

Brest, , France

Hopital Cote De Nacre

Caen, , France

CHU Hopital Gabriel Montpied

Clermont-Ferrand, , France

CH St Vincent de Paul

Lille, , France

Hopital Central - CHU de Nancy

Nancy, , France

Hopital Hautepierre - CHU Strasbourg

Strasbourg, , France

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

Dresden, , Germany

Universitätsmedizin Greifswald

Greifswald, , Germany

Medizinische Hochschule Hannover, Klinik für Neurologie

Hanover, , Germany

Universität Leipzig

Leipzig, , Germany

Universitätsklinikum Münster

Münster, , Germany

Universitätsklinikum Tübingen, Zentrum für Neurologie

Tübingen, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Deutsche Klinik für Diagnostik

Wiesbaden, , Germany

Hospital Eginition

Athens, , Greece

401 Military Hospital of Athens

Athens, , Greece

Semmelweis Egyetem Idegsebeszeti és Neurointervencios Klinika

Budapest, , Hungary

UNO Medical Trials Kft.

Budapest, , Hungary

Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

Somogy Megyei Kaposi Mor Oktato Korhaz

Kaposvár, , Hungary

Kistarcsai Flor Ferenc Korhaz

Kistarcsa, , Hungary

A. O. U. Federico II

Napoli, Campania, Italy

AOU Seconda Università degli Studi

Napoli, Campania, Italy

Azienda Ospedaliera Sant'Andrea

Rome, Lazio, Italy

Ospedale S.Antonio Abate

Gallarate, Lombardy, Italy

IRCCS Ospedale San Raffaele

Milan, Lombardy, Italy

IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla

Pavia, Lombardy, Italy

AOU Città della Salute e della Scienza

Turin, Piedmont, Italy

Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.

Guadalajara, Jalisco, Mexico

Clinstile S.A de C.V.

Mexico City, Mexico CITY (federal District), Mexico

Neurociencias Prisma, A.C

San Luis Potosí City, San Luis Potosí, Mexico

Grupo Médico Camino S.C.

México, , Mexico

Hospital Nacional Guillermo Almenara Irigoyen

La Victoria, Lima, , Peru

Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo

Lima, , Peru

Hospital Nacional Dos de Mayo

Lima, , Peru

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, , Poland

COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika

Gdansk, , Poland

MA-LEK Clinical Sp. Z o.o.

Katowice, , Poland

Szpital Specjalistyczny im. Rydygiera w Krakowie

Krakow, , Poland

Centrum Neurologii Krzysztof Selmaj

Lodz, , Poland

Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.

Lublin, , Poland

Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.

Oświęcim, , Poland

Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych

Plewiska, , Poland

EMC Instytut Medyczny SA

Późna, , Poland

Wojewódzki Szpital Specjalistyczny Nr 3

Rybnik, , Poland

Nmedis sp. z o.o.

Rzeszów, , Poland

Osrodek Badan Klinicznych Euromedis

Szczecin, , Poland

Centrum Medyczne NeuroProtect

Warsaw, , Poland

Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

Warsaw, , Poland

Hospital de Braga

Braga, , Portugal

Hospital Santo Antonio dos Capuchos

Lisbon, , Portugal

Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz

Lisbon, , Portugal

Hospital Geral de Santo Antonio

Porto, , Portugal

Krasnoyarsk State Medical Academy

Krasnoyarsk, Krasnoyarsk Krai, Russia

FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

Krasnoyarsk, Krasnoyarsk Krai, Russia

Research Center of Neurology of RAMS

Moscow, Moscow Oblast, Russia

Federal center of brain research and neurotechnologies

Moskva, Moscow Oblast, Russia

City Clinical Hospital #24

Moskva, Moscow Oblast, Russia

Leningrad Regional Clinical Hospital

Saint Petersburg, Sankt-Peterburg, Russia

National Center of Social Significant Disease

Saint Petersburg, Sankt-Peterburg, Russia

N.P. Bechtereva Institute of the Human Brain

Saint Petersburg, Sankt-Peterburg, Russia

City Hospital #40 of Kurortniy Administrative District

Saint Petersburg, Sankt-Peterburg, Russia

SHI Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, Sverdlovsk Oblast, Russia

Vertebronevrologiya LLC

Kazan', Tatarstan Republic, Russia

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, Ulyanovsk Oblast, Russia

Center of Cardiology and Neurology

Kirov, , Russia

Regional clinical hospital named after prof. S.V. Ochapovsky

Krasnodar, , Russia

FSBIH Siberian Regional Medical Centre of FMBA of Russia

Novosibirsk, , Russia

Perm SMA n.a. academ. E.A. Vagner

Perm, , Russia

Hospital Quiron de Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Universitario Puerta De Hierro Majadahonda

Madrid, , Spain

Hospital Universitario Virgen de Arrixaca

Murcia, , Spain

Inselspital Bern Medizin Neurologie

Bern, , Switzerland

Gazi University Medical Faculty

Ankara, , Turkey (Türkiye)

Baskent Universitesi Ankara Hastanesi

Çankaya, , Turkey (Türkiye)

Haseki Training and Research Hospital

Istanbul, , 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)

Erciyes Universitesi

Kayseri, , Turkey (Türkiye)

Kocaeli University Hospital

Kocaeli, , Turkey (Türkiye)

Ege Üniversitesi Tip Fakültesi

Lzmir, , Turkey (Türkiye)

Cumhuriyet Universitesi Tip Fakultesi

Merkez, , Turkey (Türkiye)

Mersin University Medical Faculty

Mersin, , Turkey (Türkiye)

Ondokuz Mayis University School of Medicine

Samsun, , Turkey (Türkiye)

5th Cherkasy City Center of Primary Health Care

Cherkasy, , Ukraine

SI USSRI of Medical and Social Problems of Disabilities of MOHU

Dnipro, , Ukraine

Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU

Kharkiv, , Ukraine

State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine

Kharkiv, , Ukraine

Medical Center Dopomoga Plus

Kyiv, , Ukraine

Medical Center of Private Execution First Private Clinic

Kyiv, , Ukraine

Volyn Regional Clinical Hospital

Lutsk, , Ukraine

Lvivska oblasna tsentralna likarnia

Lviv, , Ukraine

Sumy Regional Clinical Hospital

Sumy, , Ukraine

Medical Clinical Research Center of Medical Center LLC Health Clinic

Vinnytsi, , Ukraine

Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council

Zaporizhzhia, , Ukraine

Charing Cross Hospital

London, , United Kingdom

National Hospital for Neurology and Neurosurgery,

London, , United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Derriford Hospital

Plymouth, , United Kingdom

Countries

United States; Argentina; Belgium; Brazil; Bulgaria; Canada; Denmark; France; Germany; Greece; Hungary; Italy; Mexico; Peru; Poland; Portugal; Russia; Spain; Switzerland; Turkey (Türkiye); Ukraine; United Kingdom

Other Identifiers

2020-000894-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506515-18-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

BN42083

Identifier Type: -

Identifier Source: org_study_id