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

A Phase IIIB Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Antihistamine; Drug: Methylprednisolone; Drug: Ocrelizumab; Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 769
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1424
    • Centro de Especialidades Neurológicas y Rehabilitación - CENyR
  • Buenos Aires, Argentina, 1431
    • CEMIC Saavedra
  • Rosario, Argentina, S2000QGB
    • INECO
• Belgium
  • Overpelt, Belgium, 3900
    • Revalidatie en MS Centrum
• Brazil
  • Federal District
    • Brasília, Federal District, Brazil, 70200-730
      • L2 Ip Instituto de Pesquisas Clinicas Ltda ME
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-020
      • Hospital das Clinicas - UFG
  • Paraná
    • Curitiba, Paraná, Brazil, 81210-310
      • Instituto de Neurologia de Curitiba
  • Rio Grande do Sul
    • Passo Fundo, Rio Grande do Sul, Brazil, 99010-120
      • Instituto Méderi de Pesquisa e Saúde
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-001
      • Hospital Moinhos de Vento
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, Rio Grande do Sul, Brazil, 90110-000
      • IMV Pesquisa Neurológica
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89201-165
      • Clinica Neurologica
  • São Paulo
    • Campinas, São Paulo, Brazil, 13083-888
      • Hospital das Clinicas - UNICAMP
    • Santo André, São Paulo, Brazil, 09090-790
      • Praxis Pesquisa Medica
    • São Paulo, São Paulo, Brazil, 01228-000
      • CPQuali Pesquisa Clínica Ltda
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT Dr. Georgi Stranski
  • Sofia, Bulgaria, 1113
    • MHATNP Sveti Naum EAD
• Canada
  • Quebec
    • Lévis, Quebec, Canada, G6W 0M5
      • Centre de Recherche Saint-Louis
    • Montreal, Quebec, Canada, H2X 0A9
      • Chum Campus Notre Dame
    • Montreal, Quebec, Canada, H3A 2B4
      • MUCH - Montreal Neurological Institute & Hospital
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital
  • Glostrup Municipality, Denmark, 2600
    • Rigshospitalet Glostrup
• France
  • Besançon, France, 25030
    • CHU de Besancon Hopital Jean Minjoz
  • Brest, France, 29609
    • CHU Brest Hopital La Cavale Blanche
  • Caen, France, 14033
    • Hôpital Côte de Nacre
  • Clermont-Ferrand, France, 63003
    • CHU Hopital Gabriel Montpied
  • Lille, France, 59000
    • CH St Vincent de Paul
  • Nancy, France, 54035
    • Hopital Central - CHU de Nancy
  • Strasbourg, France, 67098
    • Hopital Hautepierre - CHU Strasbourg
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald
  • Hanover, Germany, 30625
    • Medizinische Hochschule Hannover, Klinik für Neurologie
  • Leipzig, Germany, 04103
    • Universität Leipzig
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen, Zentrum für Neurologie
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
  • Wiesbaden, Germany, 65191
    • Deutsche Klinik für Diagnostik
• Greece
  • Athens, Greece, 11525
    • 401 Military Hospital of Athens
  • Athens, Greece, 115 28
    • Hospital Eginition
• Hungary
  • Budapest, Hungary, 1152
    • UNO Medical Trials Kft.
  • Budapest, Hungary, 1145
    • Semmelweis Egyetem Idegsebeszeti es Neurointervencios Klinika
  • Győr, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mór Oktató Kórház
  • Kistarcsa, Hungary, 2143
    • Kistarcsai Flor Ferenc Korhaz
• Italy
  • Campania
    • Naples, Campania, Italy, 80138
      • AOU Seconda Università degli Studi
    • Naples, Campania, Italy, 80131
      • A. O. U. Federico II
  • Lazio
    • Rome, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea
  • Lombardy
    • Gallarate, Lombardy, Italy, 21013
      • Ospedale S.Antonio Abate
    • Milan, Lombardy, Italy, 20132
      • IRCCS Ospedale San Raffaele
    • Pavia, Lombardy, Italy, 27100
      • IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
  • Piedmont
    • Turin, Piedmont, Italy, 10126
      • AOU Città della Salute e della Scienza
• Mexico
  • México, Mexico, 03600
    • Grupo Médico Camino S.C.
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 06700
      • Clinstile S.A de C.V.
  • San Luis Potosí
    • San Luis Potosí City, San Luis Potosí, Mexico, 78216
      • Neurociencias Prisma, A.C
• Peru
  • La Victoria, Lima, Peru, Lima 13
    • Hospital Nacional Guillermo Almenara Irigoyen
  • Lima, Peru
    • Hospital Nacional Dos de Mayo
  • Lima, Peru, Lima 01
    • Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo
• Poland
  • Bydgoszcz, Poland, 85-796
    • Neurocentrum Bydgoszcz sp. z o.o
  • Gdansk, Poland, 80-803
    • COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika
  • Katowice, Poland, 40-595
    • MA-LEK Clinical Sp. z o.o.
  • Krakow, Poland, 31-826
    • Szpital Specjalistyczny im. Rydygiera w Krakowie
  • Lodz, Poland, 90-324
    • Centrum Neurologii Krzysztof Selmaj
  • Lublin, Poland, 20-410
    • Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
  • Oświęcim, Poland, 32-600
    • Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.
  • Plewiska, Poland, 62-064
    • Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
  • Późna, Poland, 60-309
    • EMC Instytut Medyczny SA
  • Rybnik, Poland, 44-200
    • Wojewódzki Szpital Specjalistyczny Nr 3
  • Rzeszów, Poland, 35-323
    • Nmedis sp. z o.o.
  • Szczecin, Poland, 70-215
    • Osrodek Badan Klinicznych Euromedis
  • Warsaw, Poland, 01-684
    • Centrum Medyczne Neuroprotect
  • Warsaw, Poland, 02-957
    • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga
  • Lisbon, Portugal, 1169-050
    • Hospital Santo Antonio dos Capuchos
  • Lisbon, Portugal, 1349-019
    • Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio
• Russia
  • Kirov, Russia, 610007
    • Center of Cardiology and Neurology
  • Krasnodar, Russia, 350086
    • Regional clinical hospital named after prof. S.V. Ochapovsky
  • Novosibirsk, Russia, 630007
    • FSBIH Siberian Regional Medical Centre of FMBA of Russia
  • Perm, Russia, 614990
    • Perm SMA n.a. academ. E.A. Vagner
  • Krasnoyarsk Krai
    • Krasnoyarsk, Krasnoyarsk Krai, Russia, 660022
      • Krasnoyarsk State Medical Academy
    • Krasnoyarsk, Krasnoyarsk Krai, Russia, 660037
      • FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
  • Moscow Oblast
    • Moscow, Moscow Oblast, Russia, 125367
      • Research Center of Neurology of RAMS
    • Moskva, Moscow Oblast, Russia, 117997
      • Federal center of brain research and neurotechnologies
    • Moskva, Moscow Oblast, Russia, 127015
      • City Clinical Hospital #24
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197706
      • City Hospital #40 of Kurortniy Administrative District
    • Saint Petersburg, Sankt-Peterburg, Russia, 197110
      • National Center of Social Significant Disease
    • Saint Petersburg, Sankt-Peterburg, Russia, 197376
      • N.P. Bechtereva Institute of the Human Brain
  • Sverdlovsk Oblast
    • Yekaterinburg, Sverdlovsk Oblast, Russia, 620102
      • SHI Sverdlovsk Regional Clinical Hospital #1
  • Tatarstan Republic
    • Kazan', Tatarstan Republic, Russia, 420047
      • Vertebronevrologiya LLC
  • Ulyanovsk Oblast
    • Ulyanovsk, Ulyanovsk Oblast, Russia, 432063
      • Ulyanovsk Regional Clinical Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Murcia, Spain
    • Hospital Universitario Virgen de Arrixaca
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Quiron de Madrid
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern Medizin Neurologie
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06500
    • Gazi University Medical Faculty
  • Center, Turkey (Türkiye), 58060
    • Cumhuriyet Universitesi Tip Fakultesi
  • Istanbul, Turkey (Türkiye), 34785
    • Sancaktepe Training and Research Hospital
  • Istanbul, Turkey (Türkiye), 42131
    • Selcuk University Medical Faculty
  • Istanbul, Turkey (Türkiye), 34098
    • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi
  • Istanbul, Turkey (Türkiye), 34096
    • Haseki Training and Research Hospital
  • Kayseri, Turkey (Türkiye), 38039
    • Erciyes Üniversitesi
  • Kocaeli, Turkey (Türkiye), 41380
    • Kocaeli University Hospital
  • Lzmir, Turkey (Türkiye), 35100
    • Ege Universitesi Tip Fakultesi
  • Mersin, Turkey (Türkiye), 33079
    • Mersin University Medical Faculty
  • Samsun, Turkey (Türkiye), 55139
    • Ondokuz Mayis University School of Medicine
  • Çankaya, Turkey (Türkiye), 06490
    • Baskent Universitesi Ankara Hastanesi
• Ukraine
  • Cherkasy, Ukraine, 18029
    • 5th Cherkasy City Center of Primary Health Care
  • Dnipro, Ukraine, 49027
    • SI USSRI of Medical and Social Problems of Disabilities of MOHU
  • Ivano-Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital
  • Kharkiv, Ukraine, 61068
    • State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
  • Kharkiv, Ukraine, 61068
    • St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU
  • Kyiv, Ukraine, 02123
    • Medical Center Dopomoga Plus
  • Lutsk, Ukraine, 43005
    • Volyn Regional Clinical Hospital
  • Lviv, Ukraine, 79010
    • Lvivska oblasna tsentralna likarnia
  • Sumy, Ukraine, 40031
    • Sumy Regional Clinical Hospital
  • Vinnytsi, Ukraine, 21009
    • Medical Clinical Research Center of Medical Center LLC Health Clinic
  • Zaporizhzhya, Ukraine, 69600
    • Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, WC1 3BG
    • National Hospital for Neurology and Neurosurgery,
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital
• United States
  • Alabama
    • Homewood, Alabama, United States, 35209
      • Alabama Neurology Associates
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • 21st Century Neurology
  • California
    • Irvine, California, United States, 92697
      • University of California Irvine
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Fort Collins, Colorado, United States, 80524
      • Advanced Neurosciences Research LLC
  • Florida
    • Clearwater, Florida, United States, 33761
      • MS and Neuromuscular Center of Excellence
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Kentucky
    • Nicholasville, Kentucky, United States, 40356
      • Baptist Health Lexington
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • International Neurorehabilitation Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Institute for Neurological Disorders
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Neptune City, New Jersey, United States, 07753
      • Jersey Shore University Medical Centre
  • New York
    • Great Neck, New York, United States, 11021
      • Northwell Health
    • New York, New York, United States, 10075
      • Lenox Hill Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
    • Nashville, Tennessee, United States, 37205
      • Advanced Neurosciences Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • San Antonio, Texas, United States, 78258
      • Lone Star Neurology of San Antonio
    • Sherman, Texas, United States, 75092
      • Texas Institute for Neurological Disorders
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wheaton Franciscan Healthcare - St. Francis Outpatient Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: Non-Investigational Medicinal Product; Drug: Methylprednisolone; Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.; Other Names: Non-Investigational Medicinal Product; Drug: 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); Other Names: Ocrevus; 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.; Other Names: Ocrevus
Active Comparator: 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.	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.; Other Names: Non-Investigational Medicinal Product; Drug: Methylprednisolone; Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.; Other Names: Non-Investigational Medicinal Product; Drug: 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); Other Names: Ocrevus; 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.; Other Names: Ocrevus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 4.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of 24-week cCDP (cCDP24)	Time to onset of a 24 week cCDP=first occurrence of a 24-week cCDP according to at least 1 of 3 criteria: 1) CDP=24-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 24-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 24-week CI of ≥20% FB in T25FWT score OR 3) 24-week CI of ≥ 20% FB in 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 4.5 years
Time to Onset of cCDP12 Independent of Protocol-defined Relapses (PDR) or Progression Independent of Relapse Activity (PIRA)	Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of 3 criteria: 1) CDP=12-week CI from baseline in 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 T25FWT score OR 3) 12-week CI of ≥ 20% FB in 9-HPT score. EDSS score, T25FWT & 9-HPT are the same as defined in primary outcome measure. Protocol-defined relapse=occurrence of new or worsening neurological symptoms attributable to MS and immediately preceded by a relatively stable or improving neurological state of at least 30 days. Symptoms persist for at least 24 hours & accompanied by objective neurological worsening consistent with an increase of one of the following: Half a step (0.5 point) on the EDSS; Two points on one of the functional system scores (FSS) (pyramidal, ambulation, cerebellar, brainstem, sensory, or visual); One point on ≥2 more of the FSS.	Up to approximately 4.5 years
Time to Onset of 12-week Confirmed Disability Progression (CDP12)	CDP was defined as a 12-week confirmed increase from baseline in EDSS score of ≥1.0 point in participants with a baseline EDSS score of ≤5.5 or a 12-week CI ≥0.5 points in participants with a baseline EDSS score of >5.5. The EDSS was used to measure changes in the disability level of participants with MS over time. EDSS is based on a standard neurological examination, incorporating functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral [or mental]) that are rated and then scored as a FSS, and ambulation, which is scored as ambulation score. Each FSS is an ordinal clinical rating scale where score range from 0 to 5 or 6, and ambulation score that is rated from 0 to 16. These ratings along with observations and assistive devices were then used to determine the total EDSS score. The total EDSS score ranges from 0 (normal) to 10.0 (death) in 0.5-point steps.	Up to approximately 4.5 years
Time to ≥ 20% Increase in 12-week Confirmed T25FWT	T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. A 20% change from baseline of the averaged T25FWT was considered clinically meaningful.	Up to approximately 4.5 years
Time to Onset of 12-week Confirmed ≥ 4-point Worsening in Symbol Digit Modalities Test (SDMT)	The SDMT is a performance measure that demonstrated sensitivity in detecting the presence of cognitive impairment and changes in cognitive functioning over time & in response to treatment. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants were asked to pair specific numbers with given geometric figures within 90 seconds. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement. A four-point change from baseline was considered clinically meaningful.	Up to approximately 4.5 years
Time to Onset of 24-week Confirmed ≥ 8-point Increase in 12-Item Multiple Sclerosis Walking Scale (MSWS-12)	The MSWS-12 was a 12-item self-report measure of the impact of MS on the participant's ability to walk during the past 2 weeks. Each item was scored on a 5-point Likert scale ranging from 1 (not at all) to 5 (extremely likely). Scores were summed and linearly converted to a 0-100 scale with higher scores indicating greater impact of MS on walking ability. An 8-point change was considered clinically meaningful.	Up to approximately 4.5 years
Annual Rate of Percent Change From Baseline in Total Brain Volume	Brain volume was measured using magnetic resonance imaging (MRI) scans. Mean difference in annual rate of percent change from baseline in total brain volume between the higher and approved dose of ocrelizumab arms in participants with RMS where no treatment discontinuation nor initiation of alternative MS treatment occurred, are reported.	Up to approximately 4.5 years
Annual Rate of Percent Change From Baseline in Thalamic Volume	Thalamic volume was measured using MRI scans. Mean difference in annual rate of percent change from baseline in thalamic volume between the higher and approved dose of ocrelizumab arms in participants with RMS where no treatment discontinuation nor initiation of alternative MS treatment occurred, are reported.	Up to approximately 4.5 years
Ratio of Fold Change From Baseline in Neurofilament Light Chain (NfL) Levels at Week 96	NfL is a biomarker of neuroinflammation in CSF. Ratio of the mean change from baseline in NfL at Week 96 between the higher and approved dose of ocrelizumab arms in PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric means at Week 96 vs baseline).	At Week 96
Fold Change From Baseline in NfL Levels at Week 96 Within the Higher Dose Ocrelizumab Group	NfL is a biomarker of neuroinflammation in CSF. Mean change from baseline in NfL at Week 96 for PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab higher dose group have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric mean at Week 96 vs baseline).	At Week 96
Fold Change From Baseline in NfL Levels at Week 96 Within the Approved Dose Ocrelizumab Group	NfL is a biomarker of neuroinflammation in CSF. Mean change from baseline in NfL at Week 96 for PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab 600 mg group have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric mean at Week 96 vs baseline).	At Week 96
Number of Participants With Adverse Events (AEs)	AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	From initiation of study drug up to approximately 6.8 years
Area Under the Serum Concentration-time Curve (AUC) of Ocrelizumab Over the First Dosing Interval		Day 1 to Week 24
B-cell Levels in Blood		Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216
Percent Change From Baseline in B-cell Levels		Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216
Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood		Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216
Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood		Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216
Percentage of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab	Participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer unit (t.u.) greater than the baseline titer result. Percentages have been rounded off.	Up to approximately 4.5 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Hauser SL, Giovannoni G, Montalban X, Oh J, Bar-Or A, Sormani MP, Weber MS, Stoll S, Nicholas JA, Nehrych T, Bonek R, Selmaj K, Maciejowski M, Zecevic D, Raposo C, Owen R, Bonati U, Madjar K, Harfst E, Wang Q, Raievska A, Manfrini M, Schneble HM, Kappos L; MUSETTE and GAVOTTE Study Groups. Efficacy and safety of a bodyweight-adjusted higher dose of ocrelizumab in relapsing (MUSETTE) and primary progressive (GAVOTTE) multiple sclerosis: two multicentre, randomised, double-blind, parallel-group phase 3b trials. Lancet. 2026 May 30;407(10544):2180-2194. doi: 10.1016/S0140-6736(26)00147-9.

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2020
• Primary Completion (Actual): June 30, 2025
• Study Completion (Estimated): September 8, 2027

Study Registration Dates

• First Submitted: September 9, 2020
• First Submitted That Met QC Criteria: September 9, 2020
• First Posted (Actual): September 16, 2020

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: June 26, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Primary Progressive Multiple Sclerosis; Higher Dose of CD20 Antibody Ocrelizumab; Efficacy, Safety and Pharmacokinetics
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Pathological Conditions, Signs and Symptoms; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Histamine Agents; Neurotransmitter Agents; Pharmacologic Actions; Chemical Actions and Uses; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Pregnadienetriols; Prednisolone; Methylprednisolone; Histamine Antagonists; ocrelizumab
• Other Study ID Numbers: BN42083; 2020-000894-26 (EudraCT Number); 2023-506515-18-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No