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

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 pharmacokinetics of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks in participants with PPMS, in comparison to the approved 600 mg dose of ocrelizumab.

Study Overview

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

Detailed Description

Participants will be treated for a minimum of 120 weeks in the double-blind phase. Upon positive primary results after the double-blind phase, an optional higher dose extension treatment (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 lower limit of normal.

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

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BN42083 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. and Canada); Email: Global-Roche-Genentech-Trials@gene.com

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1424
    • Centro de Especialidades Neurológicas y Rehabilitación - CENyR
  • Buenos Aires, Argentina, C1431FWO
    • CEMIC Saavedra
  • Rosario, Argentina, S2000QGB
    • INECO; Neurociencias
• Belgium
  • Overpelt, Belgium, 3900
    • Revalidatie en MS Centrum
• Brazil
  • DF
    • Brasilia, DF, Brazil, 70200-730
      • L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar
  • GO
    • Goiania, GO, Brazil, 74605-020
      • Hospital das Clinicas - UFG
  • PR
    • Curitiba, PR, Brazil, 81210-310
      • Instituto de Neurologia de Curitiba
  • RS
    • Passo Fundo, RS, Brazil, 99010-120
      • Instituto Méderi de Pesquisa e Saúde
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
    • Porto Alegre, RS, Brazil, 90110-000
      • IMV Pesquisa Neurológica
    • Porto Alegre, RS, Brazil, 90035-000
      • Hospital Moinhos de Vento
  • SC
    • Joinville, SC, Brazil, 89202-190
      • Clinica Neurologica; Neurocirurgica de Joinville
  • SP
    • Campinas, SP, Brazil, 13083-887
      • Hospital das Clinicas - UNICAMP
    • Santo Andre, SP, Brazil, 09090-790
      • Praxis Pesquisa Medica
    • Sao Paulo, SP, Brazil, 01228-000
      • CPQuali Pesquisa Clínica Ltda
• Bulgaria
  • Pleven, Bulgaria, 5800
    • UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases
  • Sofia, Bulgaria, 1113
    • MHATNP Sveti Naum EAD
• Canada
  • Quebec, Canada, G1W 4R4
    • Hotel-Dieu de Levis
  • Quebec
    • 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; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.
  • Glostrup, Denmark, 2600
    • Rigshospitalet Glostrup; Neurologisk Klinik
• France
  • Besançon, France, 25030
    • CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
  • Brest, France, 29609
    • CHU Brest Hopital La Cavale Blanche; Neurologie
  • Caen, France, 14033
    • Hopital Cote De Nacre; Unite Neurologie Generale
  • Clermont Ferrand, France, 63003
    • CHU Hopital Gabriel Montpied; Service de Neurologie
  • Lille, France, 59000
    • CH St Vincent de Paul
  • Nancy, France, 54035
    • Hopital Central - CHU de Nancy; Service de Neurologie
  • Strasbourg, France, 67098
    • Hopital Hautepierre - CHU Strasbourg; Service de Neurologie
• Germany
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
  • Greifswald, Germany, 17475
    • Universitätsmedizin Greifswald; Klinik und Poliklinik für Neurologie
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover, Klinik für Neurologie
  • Leipzig, Germany, 04103
    • Universität Leipzig; Innere Medizin, Neurologie, Dermatologie
  • Münster, Germany, 48149
    • Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen, Zentrum für Neurologie
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Neurologie
  • Wiesbaden, Germany, 65191
    • Deutsche Klinik für Diagnostik; DKD Helios Klinik Wiesbaden, Abt. Neurologie
• Greece
  • Athens, Greece, 115 25
    • 401 Military Hospital of Athens; Neurology Department
  • Athens, Greece, 115 28
    • Hospital Eginition; First Department of Neurology
  • Larisa, Greece, 411 10
    • University General Hospital of Larisa; Neurology Clinic
  • Thessaloniki, Greece, 546 36
    • AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.
• Hungary
  • Budapest, Hungary, 1152
    • UNO Medical Trials Kft.
  • Budapest, Hungary, 1145
    • Orszagos Mentalis, Ideggyogyaszati es Idegsebeszeti Intezet; Neurology
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz; Neurologiai Osztaly
  • Kaposvár, Hungary, 7400
    • Somogy Megyei Kaposi Mor Oktato Korhaz; Department of Neurology
  • Kistarcsa, Hungary, 2143
    • Kistarcsai Flor Ferenc Korhaz; Neurology and Stroke Ambulance
• Italy
  • Campania
    • Napoli, Campania, Italy, 80138
      • AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica
    • Napoli, Campania, Italy, 80131
      • A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea; UOC Neurologia
  • Lombardia
    • Gallarate, Lombardia, Italy, 21013
      • Ospedale S.Antonio Abate; Neurologia 2 ? Sclerosi Multipla e Recupero Neurologico
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
    • Pavia, Lombardia, Italy, 27100
      • IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
  • Piemonte
    • Torino, Piemonte, Italy, 10126
      • AOU Città della Salute e della Scienza; Neurologia 1
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44130
      • Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03600
      • Grupo Medico Camino S.C.
    • Mexico City, Mexico CITY (federal District), Mexico, 06700
      • Clinstile S.A de C.V.
  • SAN LUIS Potosi
    • San Luis Potosí, SAN LUIS Potosi, Mexico, 78216
      • Neurociencias Prisma, A.C
• Peru
  • La Victoria, Lima, Peru, Lima 13
    • Hospital Nacional Guillermo Almenara Irigoyen
  • Lima, Peru, 15003
    • Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia
  • Lima, Peru, Lima 01
    • Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo; Peru
• 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; Oddzia? Neurologiczny
  • Katowice, Poland, 40-595
    • MA-LEK Clinical Sp. Z o.o.
  • Krakow, Poland, 31-637
    • Szpital Specjalistyczny im. Rydygiera w Krakowie; Oddzial Neurologii i Udarow Mozgu
  • Lodz, Poland, 90-324
    • Centrum Neurologii Krzysztof Selmaj
  • Lublin, Poland, 20-410
    • Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
  • Oswiecim, 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
  • Pozna?, Poland, 60-309
    • EMC Instytut Medyczny SA
  • Rybnik, Poland, 44-200
    • Wojewódzki Szpital Specjalistyczny Nr 3
  • Rzeszów, Poland, 35-232
    • Nmedis sp. z o.o.
  • Szczecin, Poland, 70-111
    • Osrodek Badan Klinicznych Euromedis
  • Warszawa, Poland, 01-684
    • Centrum Medyczne NeuroProtect
  • Warszawa, Poland, 02-957
    • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)
  • Lisboa, Portugal, 1349-019
    • Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz; Neurologia
  • Lisboa, Portugal, 1169-050
    • Hospital Santo Antonio dos Capuchos; Servico de Neurologia
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio; Servico de Neurologia
• Russian Federation
  • Kirov, Russian Federation, 610007
    • Center of Cardiology and Neurology
  • Krasnodar, Russian Federation, 350086
    • Regional clinical hospital named after prof. S.V. Ochapovsky
  • Novosibirsk, Russian Federation, 630007
    • FSBIH Siberian Regional Medical Centre of FMBA of Russia
  • Perm, Russian Federation, 614990
    • Perm SMA n.a. academ. E.A. Vagner
  • Krasnojarsk
    • Krasnoyarsk, Krasnojarsk, Russian Federation, 660037
      • FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
    • Krasnoyarsk, Krasnojarsk, Russian Federation, 660049
      • Krasnoyarsk State Medical Academy
  • Leningrad
    • Sankt-peterburg, Leningrad, Russian Federation, 197110
      • National Center of Social Significant Disease
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 125367
      • Research Center of Neurology of RAMS
    • Moskva, Moskovskaja Oblast, Russian Federation, 117997
      • Federal center of brain research and neurotechnologies
    • Moskva, Moskovskaja Oblast, Russian Federation, 127015
      • City Clinical Hospital #24; Multipal Sclerosis department
  • Sankt Petersburg
    • Sankt-petersburg, Sankt Petersburg, Russian Federation, 197376
      • N.P. Bechtereva Institute of the Human Brain
    • St Petersburg, Sankt Petersburg, Russian Federation, 194291
      • Leningrad Regional Clinical Hospital
    • St. Petersburg, Sankt Petersburg, Russian Federation, 197706
      • City Hospital #40 of Kurortniy Administrative District
  • Sverdlovsk
    • Yekaterinburg, Sverdlovsk, Russian Federation, 620102
      • SHI Sverdlovsk Regional Clinical Hospital #1;Neurology
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420047
      • Vertebronevrologiya LLC
  • Uljanovsk
    • Ulyanovsk, Uljanovsk, Russian Federation, 432063
      • Ulyanovsk Regional Clinical Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Neurologia
  • Murcia
    • EL Palmar (EL Palmar), Murcia, Spain, 30120
      • Hospital Universitario Virgen de Arrixaca; Servicio de Neurología
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern Medizin Neurologie; Neurologische Poliklinik
• Turkey
  • Ankara, Turkey, 06500
    • Gazi University Medical Faculty
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
  • Istanbul, Turkey, 42131
    • Selcuk University Medical Faculty; Norology department
  • Istanbul, Turkey, 34785
    • Sancaktepe Training and Research Hospital; Neurology
  • Istanbul, Turkey, 34096
    • Haseki Training and Research Hospital; Department of Neurology
  • Kayseri, Turkey, 38039
    • Erciyes Universitesi; Pediatric Neurology
  • Kocaeli, Turkey, 41380
    • Kocaeli University Hospital; Department of Neurology
  • Lzmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi
  • Merkez, Turkey, 58060
    • Cumhuriyet Universitesi Tip Fakultesi; Noroloji Bolumu
  • Mersin, Turkey, 33079
    • Mersin University Medical Faculty; Neurology
  • Samsun, Turkey, 55139
    • Ondokuz Mayis University School of Medicine; Neurology
  • Çankaya, Turkey, 06490
    • Baskent Universitesi Ankara Hastanesi; Noroloji Bolumu
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital; Neurology Department
  • Kharkov, Ukraine, 61068
    • St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis
  • Lutsk, Ukraine, 43024
    • Volyn Regional Clinical Hospital
  • Chernihiv Governorate
    • Kyiv, Chernihiv Governorate, Ukraine, 02123
      • Medical Center Dopomoga Plus
  • KIEV Governorate
    • Cherkasy, KIEV Governorate, Ukraine, 18029
      • 5th Cherkasy City Center of Primary Health Care
    • Dnipro, KIEV Governorate, Ukraine, 49027
      • SI USSRI of Medical and Social Problems of Disabilities of MOHU
    • Kyiv, KIEV Governorate, Ukraine, 03037
      • Medical Center of Private Execution First Private Clinic
    • Lviv, KIEV Governorate, Ukraine, 79010
      • Lvivska oblasna tsentralna likarnia
  • Katerynoslav Governorate
    • Zaporizhzhia, Katerynoslav Governorate, Ukraine, 69600
      • Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
  • Kharkiv Governorate
    • Kharkiv, Kharkiv Governorate, Ukraine, 61068
      • State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
  • Podolia Governorate
    • Vinnytsia, Podolia Governorate, Ukraine, 21009
      • Medical Clinical Research Center of Medical Center LLC Health Clinic
  • Polissya Okruha
    • Sumy, Polissya Okruha, Ukraine, 40031
      • Sumy Regional Clinical Hospital
• United Kingdom
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, WC1 3BG
    • National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Plymouth, United Kingdom, PL6 8BT
    • 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; Stanford Neuroscience Health Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Fort Collins, Colorado, United States, 80528
      • 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
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Neptune, 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
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Center for Clinical Research
    • Nashville, Tennessee, United States, 37205
      • Advanced Neurosciences Institute
  • Texas
    • Dallas, Texas, United States, 75390-0001
      • University of Texas Southwestern Medical Center
    • San Antonio, Texas, United States, 78258
      • Neurology Center 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; Center for Neurological Disorders

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of primary progressive multiple sclerosis (PPMS).
• Expanded disability status scale (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 scale for the pyramidal system that was due to lower extremity findings at screening and baseline.
• Documented 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 less or equal to 5, disease duration must be less than 10 years; If EDSS score at screening is more than 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 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-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 intravenous (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 (1200 mg or 1800 mg) of ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the double blind treatment (DBT) phase. During the optional open-label extension (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; Ocrelizumab will be administered at a dose of 600 milligram (mg) every 24 weeks. The first dose of ocrelizumab will be administered as two 300 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion every 24 weeks.; Other Names: Ocrevus; 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 (participants's body weight <75 kg) or 1800 mg (participant's body weight >/=75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion every 24 weeks. During the optional open-label extension (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
Active Comparator: Ocrelizumab Approved Dose; Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by intravenous (IV) infusion every 24 weeks 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; Ocrelizumab will be administered at a dose of 600 milligram (mg) every 24 weeks. The first dose of ocrelizumab will be administered as two 300 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion every 24 weeks.; Other Names: Ocrevus; 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 (participants's body weight <75 kg) or 1800 mg (participant's body weight >/=75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion every 24 weeks. During the optional open-label extension (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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to onset of 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 EDSS, T25FWT or 9-HPT.	Baseline up to approximately 4.3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of 12-week CDP (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 Timed 25-Foot Walk Test (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
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
Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood		Baseline up to approximately 4.3 years
Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood in Participants with the High versus Low Affinity Fcgamma Receptor 3A (FcgR3A) Genotype per Arm		Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Change from Baseline in the Anti-Drug Antibody (ADA) Levels		Week 0, 24, 48, 72, 96, 120
Levels of Neurofilament Light Chain (NfL) in Blood		Baseline up to approximately 4.3 years
Levels of Interleukin-6 (IL-6) in Blood		Baseline up to approximately 4.3 years
Levels of Blood B-cells	Levels of blood B-cells is based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood	Baseline up to approximately 4.3 years
Levels of Lymphocytes in Blood		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
Serum Concentration of Ocrelizumab at Specified Timepoints		Weeks 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Proportion of Participants with Different DNA Genotypes		Week 0
Time to onset of 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 protocol defined relapses.	Baseline up to approximately 4.3 years
Change in NfL at Week 96	Biomarker for neurodegeneration NfL	Baseline up Week 96
Time to 12-week confirmed 8-point increase in 12-Item Multiple Sclerosis Walking Scale	Self-reported measure of the impact of MS on the individual's ability to walk	Baseline up Week 12
Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the approved dose ocrelizumab group	Biomarker for neurodegeneration NfL	Baseline up Week 96
Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the higher dose ocrelizumab group	Biomarker for neurodegeneration NfL	Baseline up Week 96
Time to onset of cCDP24 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 protocol defined relapses.	Baseline up Week 24

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 (Estimated): April 7, 2025
• Study Completion (Estimated): March 8, 2029

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 15, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

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: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Histamine Agents; Methylprednisolone; Ocrelizumab; Histamine H1 Antagonists; Histamine Antagonists
• Other Study ID Numbers: BN42083; 2020-000894-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

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