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

NCT ID: NCT04544436

Last Updated: 2025-11-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

864 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-26

Study Completion Date

2028-08-31

Brief Summary

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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 RMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.

Detailed Description

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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 low level 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

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Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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

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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

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Ocrevus Ocrevus Non-Investigational Medicinal Product Non-Investigation Medicinal Product

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of RMS
* At least two documented clinical relapses within the last 2 years prior to screening, or one clinical relapse in the year prior to screening. No relapse 30 days prior to screening and at baseline
* Participants must be neurologically stable for at least 30 days prior to randomization and baseline
* EDSS score, at screening and baseline, from 0 to 5.5 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 at screening and over four trials at baseline respectively, up to 250 (inclusive) seconds
* Documented magnetic resonance imaging (MRI) of brain with abnormalities consistent with MS at screening
* 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
* 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 primary 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 within 24 weeks prior to screening 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
* 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
* Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab - 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

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Maine Medical Center

Scarborough, Maine, United States

Site Status

Centrum Neurologii Krzysztof Selmaj

Lodz, , Poland

Site Status

North Central Neurology Associates

Cullman, Alabama, United States

Site Status

Alabama Neurology Associates

Homewood, Alabama, United States

Site Status

21st Century Neurology

Phoenix, Arizona, United States

Site Status

Profound Research, LLC

Carlsbad, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

Advanced Neurology of Colorado, LLC

Fort Collins, Colorado, United States

Site Status

Neurology Associates, PA

Maitland, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

American Health Network Institute, LLC

Avon, Indiana, United States

Site Status

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status

The NeuroMedical Clinic of Central Louisiana

Alexandria, Louisiana, United States

Site Status

Dragonfly Research, LLC

Wellesley, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Cleveland Clinic Lou Ruvo

Las Vegas, Nevada, United States

Site Status

Dent Neurological Institute

Amherst, New York, United States

Site Status

UC Health Neurology

Dayton, Ohio, United States

Site Status

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status

Abington Neurological Associates

Willow Grove, Pennsylvania, United States

Site Status

Tri-State Mountain Neurology

Johnson City, Tennessee, United States

Site Status

Hope Neurology

Knoxville, Tennessee, United States

Site Status

Bhupesh Dihenia M.D. P.A.

Lubbock, Texas, United States

Site Status

Lone Star Neurology of San Antonio

San Antonio, Texas, United States

Site Status

Evergreen MS Center

Kirkland, Washington, United States

Site Status

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

Buenos Aires, , Argentina

Site Status

CEMIC

Buenos Aires, , Argentina

Site Status

Centro de Investigaciones Médicas Tucuman

San Miguel de Tucumán, , Argentina

Site Status

Austin Hospital

Heidelberg, Victoria, Australia

Site Status

Hospital Erasme

Brussels, , Belgium

Site Status

Revalidatie en MS Centrum

Overpelt, , Belgium

Site Status

Instituto de Neurologia de Curitiba

Curitiba, Paraná, Brazil

Site Status

IMV Pesquisa Neurológica

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Clinica Neurologica

Joinville, Santa Catarina, Brazil

Site Status

CPQuali Pesquisa Clinica Ltda

São Paulo, São Paulo, Brazil

Site Status

Recherche Sepmus Inc.

Greenfield Park, Quebec, Canada

Site Status

Hotel-Dieu de Levis

Lévis, Quebec, Canada

Site Status

Rigshospitalet Glostrup

Glostrup Municipality, , Denmark

Site Status

Groupe Hospitalier Pellegrin

Bordeaux, , France

Site Status

CHU Hopital Gabriel Montpied

Clermont-Ferrand, , France

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CH St Vincent de Paul

Lille, , France

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Hôpital Charles Nicolle

Rouen, , France

Site Status

Charite - Universitätsmedizin Berlin

Berlin, , Germany

Site Status

St. Josef-Hospital, Klinik für Neurologie

Bochum, , Germany

Site Status

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

Dresden, , Germany

Site Status

Universitätsklinikum Schleswig-Holstein

Kiel, , Germany

Site Status

Universität Leipzig

Leipzig, , Germany

Site Status

Universitätsklinikum Tübingen, Zentrum für Neurologie

Tübingen, , Germany

Site Status

Universitätsklinikum Ulm

Ulm, , Germany

Site Status

Deutsche Klinik für Diagnostik

Wiesbaden, , Germany

Site Status

401 Military Hospital of Athens

Athens, , Greece

Site Status

S-Medicon Egeszsegugyi Szolgaltato Kft.

Budapest, , Hungary

Site Status

UNO Medical Trials Kft.

Budapest, , Hungary

Site Status

Somogy Vármegyei Kaposi Mór Oktató Kórház

Kaposvár, , Hungary

Site Status

Universita? G. D'Annunzio

Chieti, Abruzzo, Italy

Site Status

AOU Seconda Università degli Studi

Napoli, Campania, Italy

Site Status

AOU Seconda Università degli Studi

Napoli, Campania, Italy

Site Status

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

Rome, Lazio, Italy

Site Status

NCL Institute Neuroscience

Rome, Lazio, Italy

Site Status

Policlinico Umberto I

Rome, Lazio, Italy

Site Status

Fond. Istituto Neurologico C.Besta

Milan, Lombardy, Italy

Site Status

IRCCS Istituto Neurologico Neuromed

Pozzilli, Molise, Italy

Site Status

Hospital IV Alberto Sabogal Sologuren

Bellavista, , Peru

Site Status

Clinica Internacional

Lima, , Peru

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Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo

Lima, , Peru

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Hospital Maria Auxiliadora

Lima, , Peru

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Hospital Nacional Dos de Mayo

Lima, , Peru

Site Status

Clinica Sanchez Ferrer

Trujillo, , Peru

Site Status

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, , Poland

Site Status

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

Gdansk, , Poland

Site Status

MA-LEK Clinical Sp. Z o.o.

Katowice, , Poland

Site Status

SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM

Lodz, , Poland

Site Status

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

Lublin, , Poland

Site Status

Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych

Plewiska, , Poland

Site Status

EMC Instytut Medyczny SA

Późna, , Poland

Site Status

Nmedis sp. z o.o.

Rzeszów, , Poland

Site Status

Osrodek Badan Klinicznych Euromedis

Szczecin, , Poland

Site Status

Centrum Medyczne NeuroProtect

Warsaw, , Poland

Site Status

Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie

Warsaw, , Poland

Site Status

Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

Warsaw, , Poland

Site Status

Wojskowy Instytut Medyczny - Pa?Stwowy Instytut Badawczy

Warsaw, , Poland

Site Status

Hospital de Braga

Braga, , Portugal

Site Status

Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz

Lisbon, , Portugal

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Hospital de Santa Maria

Lisbon, , Portugal

Site Status

FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

Krasnoyarsk, Krasnoyarsk Krai, Russia

Site Status

Neiro Clinica LLC

Moscow, Moscow Oblast, Russia

Site Status

Research Center of Neurology of RAMS

Moscow, Moscow Oblast, Russia

Site Status

Federal center of brain research and neurotechnologies

Moskva, Moscow Oblast, Russia

Site Status

City Clinical Hospital #24

Moskva, Moscow Oblast, Russia

Site Status

National Center of Social Significant Disease

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

N.P. Bechtereva Institute of the Human Brain

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

City Hospital #40 of Kurortniy Administrative District

Saint Petersburg, Sankt-Peterburg, Russia

Site Status

SHI Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, Sverdlovsk Oblast, Russia

Site Status

Vertebronevrologiya LLC

Kazan', Tatarstan Republic, Russia

Site Status

KSMU Interregional Clinical Diagnostic Centre

Kazan', Tatarstan Republic, Russia

Site Status

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, Ulyanovsk Oblast, Russia

Site Status

Saratov State Medical University of RosZdrav

Saratov, , Russia

Site Status

Nebbiolo Center for Clinical Trials

Tomsk, , Russia

Site Status

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, LA Coruna, Spain

Site Status

Hospital Quiron de Madrid

Pozuelo de Alarcón, Madrid, Spain

Site Status

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, Spain

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status

Hospital Puerta del Mar

Cadiz, , Spain

Site Status

Hospital Regional Universitario de Malaga ? Hospital General

Málaga, , Spain

Site Status

Universitätsspital Basel Medizin Neurologie

Basel, , Switzerland

Site Status

Inselspital Bern Medizin Neurologie

Bern, , Switzerland

Site Status

Ospedale Regionale di Lugano - Civico

Lugano, , Switzerland

Site Status

Kocaeli University Hospital

Kocaeli, , Turkey (Türkiye)

Site Status

5th Cherkasy City Center of Primary Health Care

Cherkasy, , Ukraine

Site Status

Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?

Chernihiv, , Ukraine

Site Status

Bukovinsky SMU RMI Chernivtsi RCH

Chernivtsi, , Ukraine

Site Status

SI USSRI of Medical and Social Problems of Disabilities of MOHU

Dnipro, , Ukraine

Site Status

Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

Site Status

Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, , Ukraine

Site Status

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

Kharkiv, , Ukraine

Site Status

Medical Center of Private Execution First Private Clinic

Kyiv, , Ukraine

Site Status

Medical Center Dopomoga Plus

Kyiv, , Ukraine

Site Status

Lvivska oblasna tsentralna likarnia

Lviv, , Ukraine

Site Status

LCC "Medical center "Unimed"

Zaporizhzhia, , Ukraine

Site Status

Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council

Zaporizhzhia, , Ukraine

Site Status

Derriford Hospital

Plymouth, , United Kingdom

Site Status

Countries

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

Other Identifiers

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2020-000893-69

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-506467-34-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

BN42082

Identifier Type: -

Identifier Source: org_study_id

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