A Study of Ocrelizumab in Participants With Primary Progressive Multiple Sclerosis

A Phase III, Multicentre, Randomized, Parallel-group, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

This randomized, parallel group, double-blind, placebo controlled study will evaluate the efficacy and safety of ocrelizumab in participants with primary progressive multiple sclerosis. Eligible participants will be randomized 2 : 1 to receive either ocrelizumab or placebo.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Primary Progressive
• Intervention / Treatment: Drug: Ocrelizumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 735
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • St Vincent's Hospital Melbourne; Clinical Neuroscience and Neurological Research
• Austria
  • Innsbruck, Austria, 6020
    • Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
  • Linz, Austria, 4020
    • Kepler Universitätsklinikum GmbH - Neuromed Campus; Neurologie
  • Linz, Austria, 4021
    • Kepler Universitätskliniken GmbH - Med Campus III; Neurologie & Psychiatrie
  • Salzburg, Austria, 5020
    • Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie
  • Wien, Austria, 1090
    • Medizinische Universitat Wien Medical University of Vienna
• Belgium
  • La Louvière, Belgium, 7100
    • Chu Tivoli
  • Sijsele, Belgium, 8340
    • AZ Alma vzw (Sijsele)
• Brazil
  • GO
    • Goiania, GO, Brazil, 74653-050
      • Hospital das Clinicas - UFG;Reumatologia
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Santa Casa de Misericordia; de Belo Horizonte
  • RJ
    • Rio de Janeiro, RJ, Brazil, 21941-913
      • Hospital Universitario Clementino Fraga Filho - UFRJ
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital São Lucas - PUCRS
• Bulgaria
  • Sofia, Bulgaria, 1113
    • Shat Np Sveti Naum; 3Rd Clinic of Neurology
  • Sofia, Bulgaria, 1309
    • Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • University of British Columbia UBC Hospital; Multiple Sclerosis (MS) Clinic - Vancouver
  • Manitoba
    • Winnipeg, Manitoba, Canada, R8A 1R9
      • Health Sciences Centre
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche Sepmus Inc.
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno; Interni kardiologicka klinika
  • Praha 2, Czechia, 128 08
    • Vseobecna fakultni nemocnice v Praze; MS Centrum, Neurologicka klinika
  • Teplice, Czechia, 415 29
    • Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni
• Finland
  • Helsinki, Finland, 00290
    • Helsingin Yliopistollinen Keskussairaala
  • Tampere, Finland, 33520
    • Tampereen yliopisto; Kliinisen lääketieteen laitos, Neurologian yksikkö
  • Turku, Finland, 20520
    • Turku University Central Hospital; Pharmacy
• France
  • Bordeaux, France, 33076
    • Groupe Hospitalier Pellegrin; Service de neurochirurgie B
  • Bron, France, 69677
    • Hopital Neurologique et Neurochirurgical Pierre Wertheimer; Service de Neurologie A
  • Caen, France, 14033
    • Hopital Cote De Nacre; Unite Neurologie Generale
  • Clermont-Ferrand, France, 63003
    • Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B
  • Lille, France
    • Hopital Roger Salengro Service de Neurologie
  • Marseille, France, 13005
    • CHU de la Timone - Hopital d Adultes; Service de Neurologie
  • Montpellier, France, 34295
    • Hopital Gui de Chauliac; Neurologie
  • Nancy, France, 54035
    • CHRU Nancy; Service de neurologie
  • Nantes, France, 44805
    • Hôpital Guillaume et René Laënnec; Service Neurologie
  • Nice, France, 06002
    • Hôpital Pasteur; Service de Neurologie
  • Nimes, France, 30029
    • Groupe Hospitalo-Universitaire Caremeau; Service Neurologie
  • Paris, France, 75019
    • Fondation Rothschild; Service de Neurologie
  • Paris, France, 75651
    • Groupe Hospitalier Pitié- Salpétrière; Service Neurologie
  • Poissy, France, 78300
    • Hôpital de Poissy; Service neurologie
  • Reims, France, 51092
    • Hôpital Maison Blanche; Service de Neurologie
  • Strasbourg, France, 67091
    • Chu De Strasbourg; Hopital Civil
  • Toulouse, France, 31059
    • Hopital Purpan; Fédération de neurologie
• Germany
  • Bayreuth, Germany, 95445
    • Klinikum Bayreuth GmbH; Neurologische Klinik
  • Berg, Germany, 82335
    • Marianne-Strauß-Klinik; Behandlung Kempfen für Multip Sklero Kranke gemeinnütz GmbH
  • Berlin, Germany, 13347
    • Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
  • Berlin, Germany, 10117
    • Charite - Universitatsmedizin Berlin; Klinik fur Neurologie
  • Bochum, Germany, 44789
    • Berufsgenossenschaftliches Uni-Klinikum Bergmannsheil GmbH
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Neurologie
  • Düsseldorf, Germany, 40225
    • Heinrich Heine Universität Düsseldorf; Neurologische Klinik
  • Frankfurt am Main, Germany, 60528
    • Klinikum Joh.Wolfg.Goethe-UNI Senckenbergisches Institut für Neuroonkologie
  • Gießen, Germany, 35392
    • Universitätsklinikum Gießen und Marburg GmbH; Neurologie
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Koln, Germany, 51109
    • Kliniken der Stadt Koln gGmbH
  • Leipzig, Germany, 04103
    • Universität Leipzig; Innere Medizin, Neurologie, Dermatologie
  • Munchen, Germany, 81675
    • Klinikum rechts der Isar der Technischen Universitat Munchen
  • Münster, Germany, 48149
    • Universitätsklinikum Münster
  • Regensburg, Germany, 93053
    • Medizinische Einrichtungen des Bezirks Oberpfalz GmbH; Neurologie
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen, Zentrum für Neurologie
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm; Klinik für Neurologie
  • Wiesbaden, Germany, 65191
    • DKD Helios Klinik (Deutsche Klinik für Diagnostik GmbH)
• Greece
  • Athens, Greece, 115 25
    • 401 Military Hospital of Athens; Neurology Department
  • Thessaloniki, Greece, 546 36
    • AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.
  • Thessaloniki, Greece, 57010
    • Georgios Papanikolaou General Hosp. of Thessaloniki
• Hungary
  • Budapest, Hungary, 1204
    • Jahn Ferenc Dél-pesti Kórház és Rendelőintézet
  • Budapest, Hungary, 1145
    • Fövárosi Önkormányzat uzsoki utcai Kórház
  • Esztergom, Hungary, 2500
    • Vaszary Kolos Korhaz; Neurology
  • Pécs, Hungary, 7623
    • Pecsi Tudomanyegyetem
  • Szeged, Hungary, 6725
    • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika
  • Veszprem, Hungary, 8200
    • Veszprém Megyei Csolnoky Ferenc Kórház; Reumatológia
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center; Neurology Department
  • Jerusalem, Israel, 9112001
    • Hadassah University Hospital Ein Kerem; Neurology Department
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center; Multiple Sclerosis Clinic
  • Ramat-Gan, Israel, 5262100
    • The Chaim Sheba Medical Center; Multiple Sclerosis Center
  • Safed, Israel, 13100
    • Medical Center Ziv Safed; Neurology Department
  • Tel Aviv, Israel, 6423906
    • Tel Aviv Sourasky Medical Center; Department of Neurology
• Italy
  • Liguria
    • Genova, Liguria, Italy, 16132
      • A.O. Universitaria S. Martino Di Genova
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Hospital San Raffaele
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
      • Azienda Sanitaria Ospedaliera S. Luigi Gonzaga; Centro Regionale Sclerosi Multipla - Neurologia II
  • Sardegna
    • Cagliari, Sardegna, Italy, 09126
      • Ospedale Binaghi; Centro Sclerosi Multipla
• Lithuania
  • Kaunas, Lithuania, 50009
    • Hospital of Lithuanian University of Health. Sciences Kaunas Clinics
  • Klaipeda, Lithuania, 92288
    • Klaipeda University Hospital Public Institution
  • Siauliai, Lithuania, 76231
    • Siauliai Hospital
• Mexico
  • Aguascalientes, Mexico, 20127
    • Instituto Biomedico De Investigacion A.C.
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 14390
      • Instituto Nacional de Neurologia y Neurocirugia
    • Mexico, Mexico CITY (federal District), Mexico, 3600
      • Eleccion Salud SC
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64620
      • Centro de Estudios Clinicos y Espec. Med. SC
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC; Afdeling Neurologie
  • Sittard-Geleen, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum - Sittard Geleen
• New Zealand
  • Hamilton, New Zealand, 3240
    • Waikato Hospital; Neurology
  • Wellington, New Zealand, 6021
    • Wellington Hospital; Department of Neurology
• Norway
  • Oslo, Norway, 0407
    • Oslo universitetssykehus HF, Ullevål; Nevrologisk avdeling
• Peru
  • Bellavista, Peru, Callao 2
    • Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion
  • Lima, Peru, 18
    • Clinica Anglo Americana
  • Lima, Peru, Lima 1
    • Hospital Nacional Dos de Mayo - Centro de Investigacion en Oncología
• Poland
  • Bialystok, Poland, 15-402
    • Niepubliczny Zaklad Opieki Zdrowotnej KENDRON ; Poradnia Neurologiczna
  • Jaroslaw, Poland, 37-500
    • Akson - Clinical Research Maciejowski - Bielecki Sp. Jawna
  • Katowice, Poland, 40-594
    • Diagnomed Clinical Research Sp. z o.o.
  • Katowice, Poland, 40-686
    • Niepubliczny Zaklad Opieki Zdrowotnej; Neuro-Medic
  • Konskie, Poland, 26-200
    • Zespol Opieki Zdrowotnej w Konskich; Oddzial Neurologiczny
  • Lodz, Poland, 90-153
    • SPZOZ Uni. Szpital Kliniczny nr 1 im. Norberta Barlickiego Uni. Medycznego w Lodzi ; Neurologii
  • Lublin, Poland, 20-954
    • Samodzielny Publiczny Szpital Kliniczny nr 4 w Lublinie; Klinika Neurochirurgii i Neurochirurgii Dzi
• Portugal
  • Almada, Portugal, 2801-951
    • Hospital Garcia de Orta; Servico de Neurologia
  • Amadora, Portugal, 2720-276
    • Hospital Prof. Dr. Fernando Fonseca; Servico de Neurologia
  • Coimbra, Portugal, 3000-075
    • HUC; Servico de Neurologia
  • Coimbra, Portugal, 3041-801
    • Hospital Geral; Servico de Neurologia
  • Lisboa, Portugal, 1649-035
    • Hospital de Santa Maria; Servico de Neurologia
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio; Servico de Neurologia
• Romania
  • Bucharest, Romania, 011461
    • Elias Emergency University Hospital Neurology Dept; Neurology Department
  • Campulung, Romania, 115100
    • SC Clubul Sanatatii SRL
  • Targu Mures, Romania, 540136
    • Spitalul Clinic Judetean de Urgenta Targu Mures; Clinica Neurologie
  • Timi?oara, Romania, 300595
    • Timisoara Emergency County Clinical Hospital
• Russian Federation
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420103
      • Research Medical Complex "Vashe Zdorovie"; Neurology Department
• Spain
  • Alicante, Spain, 03010
    • Hospital General Univ. de Alicante
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Neurologia
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial; Servicio de Neurologia
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau; Servicio de Neurologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Madrid, Spain, 28006
    • Universitario de La Princesa; Servicio de Neurología
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Neurología
  • Malaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya; Servicio de Neurologia
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Girona
    • Salt, Girona, Spain, 17190
      • Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Neurologia
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20014
      • Hospital Donostia
  • LA Coruña
    • Santiago de Compostela, LA Coruña, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS) ; Intermedios y Urgencias Pediatricas
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto Servicio de Neurologia
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel; Neurologie
  • Lugano, Switzerland, 6903
    • Ospedale Regionale di Lugano - Civico; Neurologia
• Ukraine
  • Dnipropetrovsk, Ukraine, 49027
    • Ukrainian State Inst. of Med. and Social Problems of Disability; Neuro
  • Dnipropetrovsk, Ukraine, 49044
    • Dnipropetrovsk State Medical Academy; Dept of Neurology
  • Kharkiv, Ukraine, 61176
    • Kh. Med. Ac. of P.-Gr. Ed.; Cl. Cen. Hosp. of UkrZal.; 3rd Dept. Neurology
  • Kharkov, Ukraine, 61068
    • Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology
  • Kyiv, Ukraine, 03110
    • Kyiv City Clinical Hospital #4 MAHC of Kyiv; Chair of Neurology
  • Lutsk, Ukraine, 43024
    • Volyn Regional Clinical Hospital
  • Lviv, Ukraine, 79010
    • Lviv Regional Clinical Hospital; Department of Neurology
  • Vinnytsya, Ukraine, 21018
    • Vinnytsya National Med. Uni. n.a. M.I. Pyrohov; Dept. of Neurology #3
  • Chernihiv Governorate
    • Chernivtsi, Chernihiv Governorate, Ukraine, 58022
      • CNPE City Clinical Hospital #3 of Chernivtsi City Council
  • KIEV Governorate
    • Kyiv, KIEV Governorate, Ukraine, 04107
      • Municipal Non-profit Enterprise of Kyiv Regional Council Kyiv Regional Clinical Hospital
  • Kherson Governorate
    • Odesa, Kherson Governorate, Ukraine, 65025
      • Municipal Non-profit Enterprise Odessa Regional Clinical Hospital of Odessa Regional Council
• United Kingdom
  • Liverpool, United Kingdom, L9 7LJ
    • Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT
  • London, United Kingdom, E1 2ES
    • Barts and the London NHS Trust
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital; Neurology
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary; Neurology Dept.
  • Nottingham, United Kingdom, NG7 2UH
    • Uni Hospital Queens Medical Centre; Neurology
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurology Clinic
    • Phoenix, Arizona, United States, 85006
      • Phoenix Neurological Associates Ltd
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic- Scottsdale
  • Arkansas
    • Phoenix, Arkansas, United States, 85032-2181
      • Arizona Neuroscience Research LLC
  • California
    • Berkeley, California, United States, 94705
      • Sutter East Bay Medical Foundation
    • Newport Beach, California, United States, 92663
      • MS Center of Southern California
    • Sacramento, California, United States, 95817
      • Univ of CA Davis Med Ctr; Neurology
    • San Francisco, California, United States, 94143
      • Univ of CA San Francisco; Department of Neurology
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado; Anschutz Medical Campus Department of Neurology
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine; Dept. of Neurology Movement Disorder Center
    • Vero Beach, Florida, United States, 32960
      • Vero Beach Neurology And Research Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Cancer Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Prairie Village, Kansas, United States, 66206
      • MidAmerica Neuroscience Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University; Department of Neurology
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System; Neurology & Neurosurgery
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Institute for Neurological Disorders
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • University of Minnesota; Clin. Neuro Research Unit
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine; Department of Neurology
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico; MS Specialty Clinic
  • New York
    • Mineola, New York, United States, 11501
      • Winthrop University Hospital
    • New York, New York, United States, 10021
      • Weill Medical College of Cornell University; Judith Jaffe MS Ctr
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine; Neurology
    • Patchogue, New York, United States, 11772
      • Comprehensive MS Care Center at South Shore Neurologic Assoc.
    • Stony Brook, New York, United States, 11794
      • Neurology Assoc of Stony Brook
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas Medical Center; Ms Center
    • Raleigh, North Carolina, United States, 27607-6520
      • Raleigh Neurology Associates
  • Ohio
    • Columbus, Ohio, United States, 43221
      • The Ohio State University Wexner Medical Center; Department of Neurology
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation; MS Center of Excellence
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Trustees of the University of Pennsylvania; Neurology
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • The Neurology Foundation, Inc.
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
  • Texas
    • Dallas, Texas, United States, 75390-8897
      • University of Texas Southwestern
    • Houston, Texas, United States, 77030
      • Maxine Mesinger MS Clinic/Baylor College of Medicine; Neurology
  • Virginia
    • Richmond, Virginia, United States, 23229
      • Neurological Associates, Inc.
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Institute; Multiple Sclerosis Center

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 (according to revised McDonald criteria)
• EDSS at screening from 3 to 6.5 points
• Disease duration from onset of MS symptoms less than (<) 15 years if EDSS greater than (>) 5.0; <10 years if EDSS greater than or equal to (>/=) 5.0
• Sexually active male and female participants of reproductive potential must use two methods of contraception throughout the study treatment phase and for 48 weeks after the last dose

Exclusion Criteria:

• History of relapsing remitting MS, secondary progressive, or progressive relapsing MS at screening
• Inability to complete an MRI (contraindications for MRI)
• Known presence of other neurologic disorders
• Known active infection or history of or presence of recurrent or chronic infection
• History of cancer, including solid tumors and hematological malignancies (except for basal cell, in situ squamous cell carcinomas of the skin and in situ carcinoma of the cervix that have been excised and resolved)
• Previous treatment with B-cell targeted therapies (e.g. rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
• Any previous treatment with lymphocyte trafficking blockers, with alemtuzumab, anti-cluster of differentiation 4 (CD4), cladribine, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study

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: Placebo; Participants with primary progressive multiple sclerosis (PPMS) received placebo matched to ocrelizumab at a schedule interval of 24 weeks up to at least 120 weeks.	Drug: Ocrelizumab; Two IV infusions of 300 mg in each treatment cycle of double blind treatment period; two IV infusions of ocrelizumab 300 mg for Cycle 1 and single IV infusion of ocrelizumab 600 mg for subsequent cycles in OLE phase.; Other: Placebo; Two IV infusions of placebo matched to ocrelizumab in each treatment cycle of double blind treatment period.
Placebo Comparator: Ocrelizumab 600 mg; Participants with PPMS received ocrelizumab as two IV infusions of 300 mg separated by 14 days at a scheduled interval of every 24 weeks up to at least 120 weeks.	Drug: Ocrelizumab; Two IV infusions of 300 mg in each treatment cycle of double blind treatment period; two IV infusions of ocrelizumab 300 mg for Cycle 1 and single IV infusion of ocrelizumab 600 mg for subsequent cycles in OLE phase.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 12 Weeks During the Double-Blind Treatment Period	The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit >=12 weeks (>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of >= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is <=5.5 points (inclusive), or an increase of >=0.5 points, if baseline EDSS is >5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.	Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of Clinical Disability Progression (CDP) Sustained for at Least 24 Weeks During the Double-Blind Treatment Period	The time to onset of CDP was defined as time from baseline to first disability progression, which is confirmed at next regularly scheduled visit >=12 weeks (>=84 days) after initial disability progression. Baseline for time to onset of CDP is the date of randomization, independent of the first day of dosing. Disability progression is defined as an increase of >= 1.0 point from baseline expanded disability status scale (EDSS) score, if baseline EDSS value is <=5.5 points (inclusive), or an increase of >=0.5 points, if baseline EDSS is >5.5 points. The total EDSS score ranges from 0 (normal) to 10 (death due to multiple sclerosis). The randomized participants who did not receive any treatment were censored at days 0 in each Arm.	Maximal follow up: 216 weeks for Placebo arm and 217 weeks for Ocrelizumab arm
Percent Change From Baseline in Timed 25-Foot Walk (T25-FW) at Week 120		Baseline, Week 120
Percent Change From Baseline in Total Volume of T2 Lesions at Week 120		From Baseline to Week 120
Percent Change in Total Brain Volume From Week 24 to Week 120		From Week 24 to Week 120
Change in From Baseline Physical Component Summary Score (PCS) SF- 36 Health Survey (SF-36) at Week 120	The SF-36v2 is a 36-item, self- reported, generic measure of quality of life that has been widely used in multiple disease areas. It is composed of 8 health domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The PCS score was derived based on the SF-36 V2 User's Manual. Scoring for PCS involves (a) recoding item response values, (b) summing recoded response values for all items in a given scale to obtain the scale raw score, (c) transforming scale raw score to a 0-100 score. The PCS score was computed by (a) multiplying each health domain z score by a scale-specific physical factor score coefficient, (b) summing the resulting products, (c) converting the product total to T score. The total score ranges from 0-100, higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	From Baseline to Week 120
Number of Participants With at Least One Adverse Event (AE)	AEs included infusion related reactions (IRRs) and serious multiple sclerosis (MS) relapses, but excluded non-serious MS relapses.	From baseline to 9 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Arnold DL, Sprenger T, Bar-Or A, Wolinsky JS, Kappos L, Kolind S, Bonati U, Magon S, van Beek J, Koendgen H, Bortolami O, Bernasconi C, Gaetano L, Traboulsee A. Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS. Mult Scler. 2022 Oct;28(12):1927-1936. doi: 10.1177/13524585221097561. Epub 2022 Jun 7.
• Wolinsky JS, Arnold DL, Brochet B, Hartung HP, Montalban X, Naismith RT, Manfrini M, Overell J, Koendgen H, Sauter A, Bennett I, Hubeaux S, Kappos L, Hauser SL. Long-term follow-up from the ORATORIO trial of ocrelizumab for primary progressive multiple sclerosis: a post-hoc analysis from the ongoing open-label extension of the randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2020 Dec;19(12):998-1009. doi: 10.1016/S1474-4422(20)30342-2. Epub 2020 Oct 29. Erratum In: Lancet Neurol. 2020 Nov 17;:
• Fox EJ, Markowitz C, Applebee A, Montalban X, Wolinsky JS, Belachew S, Fiore D, Pei J, Musch B, Giovannoni G. Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial. Mult Scler. 2018 Dec;24(14):1862-1870. doi: 10.1177/1352458518808189. Epub 2018 Nov 12.
• Wolinsky JS, Montalban X, Hauser SL, Giovannoni G, Vermersch P, Bernasconi C, Deol-Bhullar G, Garren H, Chin P, Belachew S, Kappos L. Evaluation of no evidence of progression or active disease (NEPAD) in patients with primary progressive multiple sclerosis in the ORATORIO trial. Ann Neurol. 2018 Oct;84(4):527-536. doi: 10.1002/ana.25313.
• Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, de Seze J, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Rammohan KW, Selmaj K, Traboulsee A, Sauter A, Masterman D, Fontoura P, Belachew S, Garren H, Mairon N, Chin P, Wolinsky JS; ORATORIO Clinical Investigators. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):209-220. doi: 10.1056/NEJMoa1606468. Epub 2016 Dec 21.
• Butzkueven H, Spelman T, Horakova D, Hughes S, Solaro C, Izquierdo G, Kubala Havrdova E, Grand'Maison F, Prat A, Girard M, Hupperts R, Onofrj M, Lugaresi A, Taylor B; MSBase Study Group; Giovannoni G, Kappos L, Hauser SL, Montalban X, Craveiro L, Freitas R, Model F, Overell J, Muros-Le Rouzic E, Sauter A, Wang Q, Wormser D, Wolinsky JS. Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry. Eur J Neurol. 2022 Apr;29(4):1082-1090. doi: 10.1111/ene.14824. Epub 2021 May 6.

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2011
• Primary Completion (Actual): July 23, 2015
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: August 28, 2010
• First Submitted That Met QC Criteria: September 2, 2010
• First Posted (Estimated): September 3, 2010

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• 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; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: WA25046; 2010-020338-25 (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/members/ourmembers/). 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).