A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis

A Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate the Efficacy and Safety of Ocrelizumab in Comparison to Interferon Beta-1a (Rebif) in Patients With Relapsing Multiple Sclerosis

This randomized, double-blind, double-dummy, parallel-group study will evaluate the efficacy and safety of ocrelizumab in comparison with interferon beta-1a (Rebif) in participants with relapsing multiple sclerosis. Participants will be randomized to receive either ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week; or interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).

Study Overview

• Status: Completed
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Interferon beta-1a; Drug: Ocrelizumab-matching placebo; Drug: Ocrelizumab; Drug: Interferon beta-1a-matching placebo

• Study Type: Interventional
• Enrollment (Actual): 835
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425BWO
    • ALPI-Inst. de Rehabilitacion Marcelo Fitte
  • Ciudad de Buenos Airesa, Argentina, C1013AAB
    • Stat Research S.A.
• Belarus
  • Minsk, Belarus, 220116
    • City Clinical Hospital #9
  • Hrodzyenskaya Voblasts'
    • Grodno, Hrodzyenskaya Voblasts', Belarus, 230017
      • Grodno State Medical University
  • Vitsyebskaya Voblasts'
    • Vitebsk, Vitsyebskaya Voblasts', Belarus, 210037
      • Vitebsk Regional Clinical Hospital
    • Vitebsk, Vitsyebskaya Voblasts', Belarus, 210023
      • Vitebsk; Regional Diagnostic Center
• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Bosnia and Herzegovina
  • Sarajevo, Bosnia and Herzegovina, 71 000
    • University Clinic Ctr Sarajevo
  • Tuzla, Bosnia and Herzegovina, 75000
    • Uni Hospital Center Tuzla
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Santa Casa de Misericordia; de Belo Horizonte
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20270-004
      • Hospital Universitario Gaffree e Guinle
  • SP
    • Campinas, SP, Brazil, 13083-887
      • Hospital das Clinicas - UNICAMP
• Bulgaria
  • Sofia, Bulgaria, 1113
    • MHATNP Sv.Naum EAD; Clinic for intensive treatment of neurology diseases
  • Sofia, Bulgaria, 1233
    • Fifth MHAT-Sofia AD; Neuro Dept with Vascular Unit
  • Sofia, Bulgaria, 1309
    • MHAT National Cardiology Hospital, EAD; Neurology
  • Sofia, Bulgaria, 1431
    • UMHAT Alexandrovska, EAD; Neurology
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Multiple Sclerosis Clinic
    • Edmonton, Alberta, Canada, T6G 2C8
      • University of Alberta; Northern Alberta Trials & Research Centre
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • Vancouver Hospital - UBC Hospital Site
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 1W2
      • Clinique NeuroOutaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche Sepmus Inc.
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
    • Montréal, Quebec, Canada, H1T 2M4
      • Hôpital Maisonneuve - Rosemont; Recherche Clinique de Neurologie
• Croatia
  • Pula, Croatia, 52100
    • General Hospital Pula
  • Varazdin, Croatia, 42000
    • General Hospital Varazdin
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb;Clinic for Neurology
  • Zagreb, Croatia, 10000
    • Uni Hospital Centre Dubrava
• Czechia
  • Brno, Czechia, 613 00
    • Fakultní Nemocnice Brno
  • Havirov, Czechia, 736 00
    • Neurospol s.r.o.
  • Pardubice, Czechia, 532 03
    • Pardubicka Krajska Nemocnice; Department of Neurology
  • Teplice, Czechia, 415 29
    • Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni
• France
  • Bron, France, 69500
    • Hôpital Neurologique Pierre Wertheimer
  • Dijon Cedex, France, 21079
    • Hôpital General - Service de neurologie; Service de neurologie
  • Lommé, France, 59462
    • Hôpital Saint Philibert
  • Paris, France, 75651
    • Groupe Hospitalier Pitie-Salpetriere
  • Reims, France, 51092
    • Hôpital Maison Blanche; Service de Neurologie
  • Toulouse, France, 31059
    • CHU toulouse - Hôpital Purpan; Departement de Neurologie
• Germany
  • Berlin, Germany, 10713
    • Sankt Gertrauden Krankenhaus; Neurologisches Facharztzentrum
  • Bonn, Germany, 53117
    • Neurologische Praxis Bonn
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf; Klinik für Neurologie
  • Essen, Germany, 45138
    • Zentrum fuer ambulante Neurologie
  • Frankfurt, Germany, 60528
    • Universitaetsklinikum Frankfurt; Klinik für Neurologie
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Mittweida, Germany, 09648
    • Ratsapotheke Mittweida
  • Muenchen, Germany, 81377
    • Klinikum Grosshadern der LMU
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
  • Ulm, Germany, 89073
    • Neurologische Gemeinschaftspraxis Dr. Lang, Prof. Schreiber, Dr. Krauß, Dr. Kornhuber
• Ireland
  • Dublin 4, Ireland
    • St Vincents University Hospital
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Policlinico Universitario Agostino Gemelli
    • Roma, Lazio, Italy, 00133
      • Azienda Ospedaliera Universitaria Policlinico Tor Vergata
  • Liguria
    • Genova, Liguria, Italy, 16132
      • A.O. Universitaria S. Martino Di Genova
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Fondazione IRCCS Istituto Neurologico Carlo Besta; Farmacia Interna
    • Montichiari, Lombardia, Italy, 25018
      • Ospedale Civile di Montichiari; Centro Sclerosi Multipla
  • Marche
    • Torrette - Ancona, Marche, Italy, 60100
      • Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona
  • Piemonte
    • Ponderano, Piemonte, Italy, 13875
      • Ospedale degli Infermi
  • Puglia
    • Acquaviva delle Fonti, Puglia, Italy, 70021
      • Ospedale Generale Regionale F. Miulli
    • San Giovanni Rotondo, Puglia, Italy, 71013
      • Ospedale Casa Sollievo Della Sofferenza IRCCS
  • Sicilia
    • Cefalu, Sicilia, Italy, 90015
      • Fond. Ist. S. Raffaele - giglio
• Mexico
  • Aguascalientes, Mexico, 20127
    • Instituto Biomedico De Investigacion A.C.
  • Chihuahua, Mexico, 31238
    • Hospital CIMA Chihuahua; Centro de Investigación Clínicatorre de Consultoriospiso 4
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44620
      • Hospital Mexico Americano SC; Departamento de Electroencefalografía
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03100
      • Mexico Centre for Clinical Research
    • Tlalnepantla de Baz, Mexico CITY (federal District), Mexico, 54055
      • Clinical Research Institute
  • Sinaloa
    • Culiacán Rosales, Sinaloa, Mexico, 80020
      • Hospital Angeles Culiacan; Neurociencias
• Norway
  • Bergen, Norway, 5053
    • Haukeland Universitetssykehus
• Poland
  • Bydgoszcz, Poland, 85-021
    • Vitamed
  • Katowice, Poland, 40-595
    • MA-LEK Clinical Sp. Z o.o.
  • Krakow, Poland, 31-505
    • Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K
  • Lodz, Poland, 90-153
    • SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM;Oddzial Kliniczny Neurologii
  • Lodz, Poland, 90-324
    • Centrum Neurologii Krzysztof Selmaj
  • Lublin, Poland, 20-954
    • Samodz.Publi.Szpital Kliniczny; nr 4 w Lublinie
  • Olsztyn, Poland, 10-561
    • Wojewodzki Specjalistyczny Szpital w Olsztynie; Oddzial Neurologiczny z Pododdzialem Udarowym
  • Siemianowice ?l?skie, Poland, 41-100
    • Neuro-Care Gabriela Klodowska
  • Warszawa, Poland, 01-684
    • mMED Maciej Czarnecki
• Russian Federation
  • Kirov, Russian Federation, 610014
    • Kirov City Clinical Hospital #1; Neurology Department
  • Nizniy Novgorod, Russian Federation, 603155
    • SBHI of Nizhny Novgorod region City Clinical Hospital #3; neurology department
  • Perm, Russian Federation, 614990
    • Perm SMA n.a. academ. E.A. Vagner
  • Saratov, Russian Federation, 410012
    • Saratov State Medical University of RosZdrav; Neurology
  • Altaj
    • Barnaul, Altaj, Russian Federation, 656024
      • State institution of health care - Territorial Clinical Hospital
  • Sankt Petersburg
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 197022
      • St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta
  • Stavropol
    • Pyatigorsk, Stavropol, Russian Federation, 357538
      • City Clinical Hospital#2
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420101
      • State autonomous institution of healthcare Inter-regional clinical and diagnostic center
• Slovakia
  • Banska Bystrica, Slovakia, 974 04
    • MUDr. Beata Dupejova Neurologicka ambulancia s.r.o
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna Nemocnica Roosevelta
  • Levoca, Slovakia, 054 01
    • Vseobecna nemocnica s poliklinikou Levoca a.s.
• Spain
  • Alicante, Spain, 03010
    • Hospital General Univ. de Alicante
  • Barcelona, Spain, 08003
    • Hospital Del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Girona, Spain, 17007
    • Hospital Universitari de Girona Dr Josep Trueta
  • Madrid, Spain, 28040
    • Hospital Universitario Clinico San Carlos
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon; Servicio de Neurologia
  • Malaga, Spain, 29010
    • Hospital Regional Universitario de Málaga
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Neurologia
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Institut Catala d?Oncologia Hospital Germans Trias i Pujol
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge; Servicio de Neurologia
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Sjukhuset; Neurology
  • Stockholm, Sweden, 171 64
    • Karolinska Universitetssjukhuset Huddinge
  • Stockholm, Sweden, 113 41
    • Karolinska Universitetssjukhuset Solna Neurology
  • Umeå, Sweden, 901 85
    • Norrlands universitetssjukhus
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty; Neurology
  • Istanbul, Turkey, 34096
    • Haseki Training and Research Hospital
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
  • Istanbul, Turkey, 34394
    • Istanbul Bilim Universty Medical Fac.
  • Izmir, Turkey, 35100
    • Ege University Medical Faculty
  • Kocaeli, Turkey, 41380
    • Kocaeli University Medical Faculty
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Univ. Med. Fac.; Neurology
  • Trabzon, Turkey, 61080
    • Karadeniz Tecnical Uni. Med. Fac.; Neurology
• Ukraine
  • Chernihiv, Ukraine, 14029
    • Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?; Neurology Department
  • Dnipropetrovsk, Ukraine, 49102
    • City Clinical Hospital #4
  • Donetsk, Ukraine, 83045
    • State Institution V.K. Gusak Institute of Urgent and Recover; Dep of Reconstructive Angioneurology a
  • Donetsk, Ukraine, 83114
    • Road Clinical Hospital of Donetsk Station; Neurology Department
  • Ivano-Frankivsk, Ukraine, 76008
    • Regional Clinical Hospital; Neurology Department
• United Kingdom
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital (Wonford)
  • London, United Kingdom, SE5 9NT
    • Kings College Hospital; Neurosciences Clinical Trials Office
  • Stoke on Trent, United Kingdom, ST4 6QG
    • City General Hospital; Department of Neurology
  • Swansea, United Kingdom, SA6 6NL
    • Morriston Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85050
      • HOPE Research Institute
    • Scottsdale, Arizona, United States, 85251
      • HonorHealth Neurology
    • Tucson, Arizona, United States, 85704
      • Territory Neurology and Research Institute
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Research, LLC
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurosciences Research LLC
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern CT PC
  • Florida
    • Hollywood, Florida, United States, 33024
      • Infinity Clinical Research
    • Miami, Florida, United States, 33136
      • University of Miami; Dept. of Neurology MS Center
    • Orlando, Florida, United States, 32806
      • Neurological Services of Orlando
    • Sarasota, Florida, United States, 34292
      • Lovelace Scientific Resources
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • Atlanta Neuroscience Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology PC
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Prairie Village, Kansas, United States, 66206
      • MidAmerica Neuroscience Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40513
      • Associates in Neurology PSC
  • Massachusetts
    • Wellesley, Massachusetts, United States, 02481
      • Dragonfly Research, LLC
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0666
      • University of Michigan Health System
    • Detroit, Michigan, United States, 48201
      • Wayne State University; Department of Neurology
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • The Minneapolis Clinic of Neurology
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital
    • Teaneck, New Jersey, United States, 07666
      • MS Comprehensive Care Center
    • Toms River, New Jersey, United States, 08755
      • Shore Neurology
  • New York
    • Latham, New York, United States, 12210
      • Empire Neurology, PC
    • New York, New York, United States, 63110
      • Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr
    • Patchogue, New York, United States, 11772
      • South Shore Neurologic Associates P.C.
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Stony Brook, New York, United States, 11790
      • SUNY At Stony Brook
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • The Neurological Institute PA
    • Hickory, North Carolina, United States, 28602
      • Neurology Associates PA
    • Raleigh, North Carolina, United States, 27607-6520
      • Raleigh Neurology Associates
  • Ohio
    • Columbus, Ohio, United States, 43801
      • Columbus Neuroscience
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Neurological Associates
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Absher Neurology PA
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
    • Knoxville, Tennessee, United States, 37934
      • Sibyl Wray MD Neurology PC
    • Nashville, Tennessee, United States, 37205
      • Advanced Neurosciences Institute
  • Texas
    • Dallas, Texas, United States, 75390-0001
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Lubbock, Texas, United States, 79410
      • Bhupesh Dihenia M.D. P.A.
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants
    • San Antonio, Texas, United States, 78258
      • Neurology Center of San Antonio
    • San Antonio, Texas, United States, 78229
      • Integra Clinical Research, Llc
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of multiple sclerosis, in accordance with the revised McDonald criteria (2010)
• At least 2 documented clinical attacks within the last 2 years prior to screening or one clinical attack in the years prior to screening (but not within 30 days prior to screening)
• Neurologic stability for greater than or equal to (>/=) 30 days prior to both screening and baseline
• Expanded Disability Status Scale (EDSS) score 0 to 5.5 inclusive

Exclusion Criteria:

• Primary progressive multiple sclerosis
• Disease duration of more than 10 years in patients with EDSS score less than or equal to (</=) 2.0 at screening
• Contraindications for MRI
• Known presence of other neurological disorders which may mimic multiple sclerosis
• Pregnancy or lactation
• Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• History of or currently active primary or secondary immunodeficiency
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Active infection, or history of or known presence of recurrent or chronic infection (for example, hepatitis B or C, Human Immunodeficiency Virus [HIV], syphilis, tuberculosis)
• History of progressive multifocal leukoencephalopathy
• Contraindications to or intolerance of oral or IV corticosteroids
• Contraindications to Rebif or incompatibility with Rebif use

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Interferon beta-1a 44 mcg SC; Interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).	Drug: Interferon beta-1a; Other Names: Rebif; Drug: Ocrelizumab-matching placebo
Experimental: Ocrelizumab; Ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week.	Drug: Ocrelizumab; Other Names: RO4964913; Drug: Interferon beta-1a-matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks In Double Blind Period	ARR was protocol-defined and calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of exposure to that treatment.	Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period	Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 12 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.	Week 104
Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment	The total number of T1 gadolinium-enhancing lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.	Baseline up to week 96
Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment	The total number of new and/or enlarging T2 lesions for all participants in the treatment group was calculated as the sum of the individual number of lesions at Weeks 24, 48, and 96.	Baseline up to week 96
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period	Disability progression was defined as an increase in the Expanded Disability Status Scale (EDSS) score of: A) >=1.0 point from the baseline EDSS score when the baseline score was less than or equal to (<=) 5.5 B) >=0.5 point from the baseline EDSS score when the baseline score was >5.5 The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined. Disability progression was considered confirmed when the increase in the EDSS was confirmed at a regularly scheduled visit at least 24 weeks after the initial documentation of neurological worsening. Participants who had initial disability progression with no confirmatory EDSS assessment and who were on treatment at time of clinical cut-off date were censored at the date of their last EDSS assessment.	Week 104
Number of T1 Hypointense Lesions During the Double-Blind Treatment	The total number of new T1-Hypo-Intense Lesions (Chronic Black Holes) for all participants in the treatment group was calculated as the sum of the individual number of new lesions at Weeks 24, 48, and 96.	Baseline up to week 96
Number of Participants With Adverse Events (AEs)	AEs included infusion related reactions (IRRs) and serious MS relapses, but excluded non-serious MS relapses. Serious Adverse Events (SAEs) included serious MS relapses and serious IRRs.	Baseline up to Week 96
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks In Double Blind Period	Disability improvement was assessed only for the subgroup of participants with a baseline EDSS score of >= 2.0. It was defined as a reduction in EDSS score of: A) >=1.0 from the baseline EDSS score when the baseline score was >=2 and <=5.5 B) >= 0.5 when the baseline EDSS score > 5.5. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). This outcome measure was considered confirmatory only when results of both studies WA21092 and WA21093 were combined.	Week 96
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96 In Double Blind Period	MSFC score consists of: A) Timed 25-Foot walk; B) 9-Hole Peg Test (9-HPT); and C) Paced Auditory Serial Addition Test (PASAT-3 version). The MSFCS is based on the concept that scores for these three dimensions (arm, leg, and cognitive function) are combined to create a single score (the MSFC) that can be used to detect change over time in a group of participants with MS. Since the three primary measures differ in what they actually measure, a common composite score for the three different measures i.e., Z- score was selected for the purpose. MSFC Score = {Z arm, average + Z leg, average + Z cognitive} / 3.0. The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each participant at each time point. A score of +1 indicates that, on average, an individual scored 1 standard deviation (SD) better than the reference population and a score of -1 indicates that an individual scored 1 SD worse than the reference population.	Baseline, Week 96
Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96 In Double Blind Period	Brain volume was recorded as an absolute "normalized" value at the baseline visit then recorded at subsequent visits as a percentage change relative to the absolute value at the baseline visit. Therefore, brain volume at Week 24 was calculated as the brain volume at the baseline visit multiplied by 1 + ([percentage change in brain volume from baseline visit to Week 24]/100). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM) using unstructured covariance matrix: Percentage Change = Brain Volume at Week 24 + Geographical Region (US vs. ROW) + Baseline EDSS (< 4.0 vs. >= 4.0) + Week + Treatment + Treatment*Week (repeated values over Week) + Brain Volume at Week 24*Week. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis).	From week 24 up to week 96
Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96 In Double Blind Period	The SF-36 is a multi-purpose, short-form health survey with 36 questions. It yields an 8-scale profile of functional health and well-being scores (domains) as well as psychometrically based physical and mental health summary measures. The SF-36 taps 8 health concepts: physical functioning, bodily pain, physical role functioning, emotional role functioning, emotional well-being, social functioning, vitality, and general health perceptions. The 8 scales are further summarized to 2 distinct higher-ordered clusters: the PCS and mental composite t-score (MCS). The range for all 8 domains as well as for the composite t- scores is from 0 to 100 with 100 as best possible health status and 0 as worst health status.	Baseline, Week 96
Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96 In Double Blind Period	NEDA was defined only for participants with a baseline EDSS score >=2.0. The EDSS scale ranges from 0 (normal neurological exam) to 10 (death due to multiple sclerosis). Participants who completed the 96- week treatment period were considered as having evidence of disease activity if at least one protocol- defined relapse (PDR), a confirmed disability progression (CDP) event or at least one MRI scan showing MRI activity (defined as Gd-enhancing T1 lesions, or new or enlarging T2 lesions) was reported during the 96-week treatment period, otherwise the participant was considered as having NEDA.	Week 96
Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC) In Double Blind Period	AUC represents total drug exposure for one dosing interval after the 4th dose.	Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab In Double Blind Period	Number of participants positive for anti-drug antibodies (ADAs) to ocrelizumab is the number of post- baseline evaluable participants determined to have treatment-induced ADA or treatment-enhanced ADA during the study period.	Baseline up to Week 96

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.
• Krishnan AP, Song Z, Clayton D, Gaetano L, Jia X, de Crespigny A, Bengtsson T, Carano RAD. Joint MRI T1 Unenhancing and Contrast-enhancing Multiple Sclerosis Lesion Segmentation with Deep Learning in OPERA Trials. Radiology. 2022 Mar;302(3):662-673. doi: 10.1148/radiol.211528. Epub 2021 Dec 14.
• Giovannoni G, Kappos L, de Seze J, Hauser SL, Overell J, Koendgen H, Manfrini M, Wang Q, Wolinsky JS. Risk of requiring a walking aid after 6.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis: Data from the OPERA I and OPERA II trials. Eur J Neurol. 2022 Apr;29(4):1238-1242. doi: 10.1111/ene.14823. Epub 2021 May 5.
• Hauser SL, Kappos L, Arnold DL, Bar-Or A, Brochet B, Naismith RT, Traboulsee A, Wolinsky JS, Belachew S, Koendgen H, Levesque V, Manfrini M, Model F, Hubeaux S, Mehta L, Montalban X. Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension. Neurology. 2020 Sep 29;95(13):e1854-e1867. doi: 10.1212/WNL.0000000000010376. Epub 2020 Jul 20.
• Kappos L, Wolinsky JS, Giovannoni G, Arnold DL, Wang Q, Bernasconi C, Model F, Koendgen H, Manfrini M, Belachew S, Hauser SL. Contribution of Relapse-Independent Progression vs Relapse-Associated Worsening to Overall Confirmed Disability Accumulation in Typical Relapsing Multiple Sclerosis in a Pooled Analysis of 2 Randomized Clinical Trials. JAMA Neurol. 2020 Sep 1;77(9):1132-1140. doi: 10.1001/jamaneurol.2020.1568.
• Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2011
• Primary Completion (Actual): May 12, 2015
• Study Completion (Actual): December 30, 2022

Study Registration Dates

• First Submitted: August 8, 2011
• First Submitted That Met QC Criteria: August 8, 2011
• First Posted (Estimated): August 9, 2011

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

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; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferons; Interferon beta-1a; Ocrelizumab; Interferon-beta
• Other Study ID Numbers: WA21093; 2010-020315-36 (EudraCT Number)