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

NCT04544436 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 3 other identifiers: BN420822020-000893-692023-506467-34-00
• Study Type: interventional
• Target: 864
• Locations: 21 countries
• Sites: 120

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

Conditions

Multiple Sclerosis

Keywords

Relapsing Remitting Multiple Sclerosis; Higher Dose of CD20 Antibody Ocrelizumab; Efficacy, Safety and Pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12)

  Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of the 3 criteria: 1) CDP=12-week confirmed increase (CI) from baseline (FB) in expanded disability status scale (EDSS) score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of \>5.5 OR 2) 12-week CI of ≥20% FB in Timed 25-foot Walk Test (T25FWT) score OR 3)12-week CI of ≥ 20% FB in 9-hole Peg Test (9-HPT) score. EDSS = disability scale that ranges in 0.5-point steps from 0 \[normal\]-10.0 \[death\]. In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.

  Up to approximately 4 years

Secondary Outcomes (16)

• Time to Onset of 24-week cCDP (cCDP24)

  Up to approximately 4 years

• Time to Onset of 48-week cCDP (cCDP48)

  Up to approximately 4 years

• Time to Onset of cCDP12 Independent of Protocol-defined Relapses (PDR) or Progression Independent of Relapse Activity (PIRA)

  Up to approximately 4 years

• Time to Onset of 12-week Confirmed Disability Progression (CDP12)

  Up to approximately 4 years

• Time to ≥ 20% Increase in 12-week Confirmed T25FWT

  Up to approximately 4 years

Study Arms (2)

Ocrelizumab Higher Dose

EXPERIMENTAL

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.

Drug: Ocrelizumab; Drug: Antihistamine; Drug: Methylprednisolone

Ocrelizumab Approved Dose

ACTIVE COMPARATOR

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.

Drug: Ocrelizumab; Drug: Antihistamine; Drug: Methylprednisolone

Interventions

Methylprednisolone DRUG

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

Also known as: Non-Investigation Medicinal Product

Ocrelizumab Approved Dose; Ocrelizumab Higher Dose

Ocrelizumab 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).

Also known as: Ocrevus

Ocrelizumab Higher Dose

Antihistamine 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.

Also known as: Non-Investigational Medicinal Product

Ocrelizumab Approved Dose; Ocrelizumab Higher Dose

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (120)

North Central Neurology Associates

Cullman, Alabama, 35058, United States

Location

Alabama Neurology Associates

Homewood, Alabama, 35209, United States

Location

21st Century Neurology

Phoenix, Arizona, 85004, United States

Location

Profound Research, LLC

Carlsbad, California, 92011, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Advanced Neurology of Colorado, LLC

Fort Collins, Colorado, 80528, United States

Location

Neurology Associates, PA

Maitland, Florida, 32751, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

American Health Network Institute, LLC

Avon, Indiana, 46123, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

The NeuroMedical Clinic of Central Louisiana

Alexandria, Louisiana, 71301, United States

Location

Maine Medical Center

Scarborough, Maine, 04074, United States

Location

Dragonfly Research, LLC

Wellesley, Massachusetts, 02481, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cleveland Clinic Lou Ruvo

Las Vegas, Nevada, 89106, United States

Location

Dent Neurological Institute

Amherst, New York, 14226, United States

Location

UC Health Neurology

Dayton, Ohio, 45417, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Abington Neurological Associates

Willow Grove, Pennsylvania, 19090, United States

Location

Tri-State Mountain Neurology

Johnson City, Tennessee, 37604, United States

Location

Hope Neurology

Knoxville, Tennessee, 37922, United States

Location

Lone Star Neurology of San Antonio

San Antonio, Texas, 78258, United States

Location

Evergreen MS Center

Kirkland, Washington, 98034, United States

Location

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

Buenos Aires, C1424, Argentina

Location

CEMIC

Buenos Aires, C1431FWO, Argentina

Location

Centro de Investigaciones Médicas Tucuman

San Miguel de Tucumán, T4000AXL, Argentina

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Hospital Erasme

Brussels, 1070, Belgium

Location

Revalidatie en MS Centrum

Overpelt, 3900, Belgium

Location

Instituto de Neurologia de Curitiba

Curitiba, Paraná, 81210-310, Brazil

Location

IMV Pesquisa Neurológica

Porto Alegre, Rio Grande do Sul, 90620-130, Brazil

Location

Clinica Neurologica

Joinville, Santa Catarina, 89201-165, Brazil

Location

CPQuali Pesquisa Clinica Ltda

São Paulo, São Paulo, 01228-000, Brazil

Location

Recherche Sepmus Inc.

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Centre de Recherche Saint-Louis

Lévis, Quebec, G6W 0M5, Canada

Location

Rigshospitalet Glostrup

Glostrup Municipality, 2600, Denmark

Location

Groupe Hospitalier Pellegrin

Bordeaux, 33076, France

Location

CHU Hopital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

CH St Vincent de Paul

Lille, 59000, France

Location

Hôpital Charles Nicolle

Rouen, 76031, France

Location

Charite - Universitätsmedizin Berlin

Berlin, 12203, Germany

Location

St. Josef-Hospital, Klinik für Neurologie

Bochum, 44791, Germany

Location

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

Dresden, 01307, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, 24105, Germany

Location

Universität Leipzig

Leipzig, 04103, Germany

Location

Universitätsklinikum Tübingen, Zentrum für Neurologie

Tübingen, 72076, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Deutsche Klinik für Diagnostik

Wiesbaden, 65191, Germany

Location

401 Military Hospital of Athens

Athens, 11525, Greece

Location

S-Medicon Egeszsegugyi Szolgaltato Kft.

Budapest, 1138, Hungary

Location

UNO Medical Trials Kft.

Budapest, 1152, Hungary

Location

Somogy Vármegyei Kaposi Mór Oktató Kórház

Kaposvár, 7400, Hungary

Location

Universita? G. D'Annunzio

Chieti, Abruzzo, 66100, Italy

Location

AOU Seconda Università degli Studi

Naples, Campania, 80131, Italy

Location

AOU Seconda Università degli Studi

Naples, Campania, 80138, Italy

Location

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

Rome, Lazio, 00133, Italy

Location

NCL Institute Neuroscience

Rome, Lazio, 00178, Italy

Location

Policlinico Umberto I

Rome, Lazio, 00185, Italy

Location

Fond. Istituto Neurologico C.Besta

Milan, Lombardy, 20133, Italy

Location

IRCCS Istituto Neurologico Neuromed

Pozzilli, Molise, 86077, Italy

Location

Hospital IV Alberto Sabogal Sologuren

Bellavista, Callao 2, Peru

Location

Clinica Internacional

Lima, 15001, Peru

Location

Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo

Lima, Lima 01, Peru

Location

Hospital Maria Auxiliadora

Lima, Lima 29, Peru

Location

Hospital Nacional Dos de Mayo

Lima, Peru

Location

Clinica Sanchez Ferrer

Trujillo, Lima 13009, Peru

Location

Neurocentrum Bydgoszcz sp. z o.o

Bydgoszcz, 85-796, Poland

Location

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

Gdansk, 80-803, Poland

Location

MA-LEK Clinical Sp. Z o.o.

Katowice, 40-571, Poland

Location

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

Lodz, 90-153, Poland

Location

Centrum Neurologii Krzysztof Selmaj

Lodz, 90-324, Poland

Location

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

Lublin, 20-410, Poland

Location

EMC Instytut Medyczny SA

Późna, 60-309, Poland

Location

Nmedis sp. z o.o.

Rzeszów, 35-323, Poland

Location

Osrodek Badan Klinicznych Euromedis

Szczecin, 70-215, Poland

Location

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

Location

Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie

Warsaw, 02-097, Poland

Location

Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

Warsaw, 02-957, Poland

Location

Wojskowy Instytut Medyczny - Pa?Stwowy Instytut Badawczy

Warsaw, 04-141, Poland

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz

Lisbon, 1349-019, Portugal

Location

Hospital de Santa Maria

Lisbon, 1649-035, Portugal

Location

FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

Krasnoyarsk, Krasnoyarsk Krai, 660037, Russia

Location

Neiro Clinica LLC

Moscow, Moscow Oblast, 117186, Russia

Location

Research Center of Neurology of RAMS

Moscow, Moscow Oblast, 125367, Russia

Location

Federal center of brain research and neurotechnologies

Moskva, Moscow Oblast, 117997, Russia

Location

City Clinical Hospital #24

Moskva, Moscow Oblast, 127015, Russia

Location

National Center of Social Significant Disease

Saint Petersburg, Sankt-Peterburg, 197110, Russia

Location

N.P. Bechtereva Institute of the Human Brain

Saint Petersburg, Sankt-Peterburg, 197376, Russia

Location

City Hospital #40 of Kurortniy Administrative District

Saint Petersburg, Sankt-Peterburg, 197706, Russia

Location

SHI Sverdlovsk Regional Clinical Hospital #1

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

Vertebronevrologiya LLC

Kazan', Tatarstan Republic, 420047, Russia

Location

KSMU Interregional Clinical Diagnostic Centre

Kazan', Tatarstan Republic, 420101, Russia

Location

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, Ulyanovsk Oblast, 432063, Russia

Location

Saratov State Medical University of RosZdrav

Saratov, 410012, Russia

Location

Nebbiolo Center for Clinical Trials

Tomsk, 634009, Russia

Location

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, LA Coruna, 15006, Spain

Location

Hospital Quiron de Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Puerta del Mar

Cadiz, 11009, Spain

Location

Hospital Regional Universitario de Malaga ? Hospital General

Málaga, 29010, Spain

Location

Universitätsspital Basel Medizin Neurologie

Basel, 4031, Switzerland

Location

Inselspital Bern Medizin Neurologie

Bern, 3010, Switzerland

Location

Ospedale Regionale di Lugano - Civico

Lugano, 6903, Switzerland

Location

Kocaeli University Hospital

Kocaeli, 41380, Turkey (Türkiye)

Location

5th Cherkasy City Center of Primary Health Care

Cherkasy, 18029, Ukraine

Location

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

Chernihiv, 14029, Ukraine

Location

Bukovinsky SMU RMI Chernivtsi RCH

Chernivtsi, 58002, Ukraine

Location

SI USSRI of Medical and Social Problems of Disabilities of MOHU

Dnipro, 49027, Ukraine

Location

Regional Clinical Hospital

Ivano-Frankivsk, 76008, Ukraine

Location

Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, 61058, Ukraine

Location

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

Kharkiv, 61068, Ukraine

Location

Medical Center of Private Execution First Private Clinic

Kyiv, 03037, Ukraine

Location

Medical Center Dopomoga Plus

Kyiv, 03143, Ukraine

Location

Lvivska oblasna tsentralna likarnia

Lviv, 79010, Ukraine

Location

LCC "Medical center "Unimed"

Zaporizhzhia, 69035, Ukraine

Location

Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council

Zaporizhzhia, 69600, Ukraine

Location

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Interventions

ocrelizumab; Histamine Antagonists; Methylprednisolone

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Histamine Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2020
• First Posted: September 10, 2020
• Study Start: November 26, 2020
• Primary Completion: December 19, 2024
• Study Completion (Estimated): August 31, 2028
• Last Updated: May 1, 2026
• Results First Posted: February 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

PT (3); AU (1); FR (4); DE (8); CA (2); HU (3); ES (6); US (24); TU (1); IT (8); UA (12); GB (1); DK (1); PE (6); CH (3); GR (1); BR (4); PL (13); AR (3); BE (2); RU (14)