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 Mederi de Pesquisa e Saude
    • 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 Médica
    • São Paulo, São Paulo, Brazil, 01228-000
      • CPQuali Pesquisa Clinica 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 Hôpital 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
    • Universitatsklinikum Munster
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen, Zentrum für Neurologie
  • Ulm, Germany, 89081
    • Universitatsklinikum 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 Mor Oktato Korhaz
  • 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 Medico 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, 194291
      • Leningrad Regional Clinical Hospital
    • 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, 03037
    • Medical Center of Private Execution First Private Clinic
  • 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
  • Zaporizhzhia, 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 Composite Confirmed Disability Progression (cCDP) Sustained for at least 12 Weeks	Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by Expanded Disability Status Scale (EDSS), Timed 25-foot Walk Test (T25FWT) or 9-hole Peg Test (9-HPT)	Baseline up to approximately 4.3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT)	The SDMT is a performance measure that has demonstrated sensitivity in detecting not only the presence of cognitive impairment but also changes in cognitive functioning over time and in response to treatment. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected orally. A four-point change from baseline is typically considered clinically meaningful.	Baseline up to approximately 4.3 years
Change in B-cell Levels in Blood		Baseline up to approximately 4.3 years
Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) Independent of Protocol-defined Relapses (PDR)	Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT independent of PDR	Baseline up to approximately 4.3 years
Time to Onset of 12-week Confirmed Disability Progression (CDP12)	CDP, defined as a sustained increase from baseline in EDSS score of ≥1.0 point in participants with a baseline EDSS score of ≤5.5 or a sustained increase of ≥0.5 points in participants with a baseline EDSS score of >5.5	Baseline up to approximately 4.3 years
Time to ≥ 20% Increase in 12-week Confirmed by T25FWT	The T25FWT is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant is directed to start at one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly and safely as possible.	Baseline up to approximately 4.3 years
Change in Neurofilament Light (NfL) at Week 96	Biomarker for neurodegeneration NfL	Baseline up to Week 96
Time to 12-week Confirmed 8-point Increase in 12-item Multiple Sclerosis Walking Scale (MSWS12)	Self-reported measure of the impact of multiple sclerosis (MS) on the individual's ability to walk	Baseline up to approximately 4.3 years
Annual Rate of Percent Change From Baseline in Total Brain Volume		Baseline up to approximately 4.3 years
Annual Rate of Percent Change From Baseline in Thalamic Volume		Baseline up to approximately 4.3 years
Change in NfL (i.e. Ratio to Baseline) at Week 96 for Participants in the Approved Dose Ocrelizumab Group	Biomarker for neurodegeneration NfL	Baseline up to Week 96
Change in NfL (i.e. Ratio to Baseline) at Week 96 for Participants in the Higher Dose Ocrelizumab Group	Biomarker for neurodegeneration NfL	Baseline up to Week 96
Time to Onset of 24-week Composite Confirmed Disability Progression (cCDP24) Independent of PDR	Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT independent of PDR	Baseline up to approximately 4.3 years
Percentage of Participants With Adverse Events (AEs)		Baseline up to approximately 8 years
Serum Concentrations of Ocrelizumab at Specified Timepoints		Weeks 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Percentage of Participants Achieving 5 or Less B-cells per Microliter of Blood		Baseline up to approximately 4.3 years
Change From Baseline in the Anti-drug Antibody (ADA) Levels		Week 0, 24, 48, 72, 96, 120

Collaborators and Investigators

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

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): March 30, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 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