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). Planned duration of double-blind treatment is 96 weeks. Participants who complete the 96-week double-blind treatment will have an option to enter a single-group, active-treatment, open-label extension period, providing they fulfill the eligibility criteria.

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): 821
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1204AAD
    • Instituto Centenario
  • Ciudad Autonoma Bs As, Argentina, C1209AAB
    • Hospital Español
  • Rosario, Argentina, S2000BZL
    • Fundacion Rosarina de Neurorehabilitacion
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital; Department of Neurology
• Austria
  • Linz, Austria, 4040
    • Barmherzige Brueder Konventspital
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint Jan
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint-Luc; Neurology
  • Roeselare, Belgium, 8800
    • AZ Delta (Campus Rumbeke)
• Brazil
  • GO
    • Goiania, GO, Brazil, 74653-050
      • Hospital das Clinicas - UFG;Reumatologia
  • RS
    • Porto Alegre, RS, Brazil, 90110-000
      • IMV Pesquisa Neurológica
  • SC
    • Joinville, SC, Brazil, 89202-190
      • Clinica Neurologica; Neurocirurgica de Joinville
• Bulgaria
  • Pleven, Bulgaria, 5800
    • MHAT Avis Medica; Neurology Department
  • Sofia, Bulgaria, 1407
    • ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine
  • Sofia, Bulgaria, 1000
    • First MHAT; Clinic of Neurology
  • Sofia, Bulgaria, 1113
    • MHATNP Sv.Naum EAD; Clinic in neurology diseases for movement disorders
  • Sofia, Bulgaria, 1606
    • Military Medical Academy; Neurology
• Chile
  • Valparaiso, Chile, 2340000
    • Hospital Carlos Van Buren
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny; Neurologicka klinika
  • Hradec Kralove, Czechia, 500 05
    • Fakultní Nemocnice Hradec Králové
  • Jihlava, Czechia, 58633
    • Nemocnice Jihlava; NEU-Neurologicke oddeleni
  • Pardubice, Czechia, 532 03
    • Krajska Nemocnice Pardubice Neurologicka Klinika
  • Prague, Czechia, 12808
    • VFN Praha Poliklinika Rs Centrum - Budova A
  • Teplice, Czechia, 415 29
    • Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni
• Estonia
  • Tallinn, Estonia, 10617
    • West Tallinn Central Hospital
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• Finland
  • Tampere, Finland, 33520
    • FinnMedi Oy
• France
  • Bordeaux, France, 33000
    • Groupe Hospitalier Pellegrin
  • Clermont Ferrand, France, 63003
    • CHU Hopital Gabriel Montpied; Service de Neurologie
  • Nancy, France, 54035
    • Hopital Central; Neurologie
  • Nimes, France, 30900
    • CHU de Nîmes Hopital Caremeau; Service de Neurologie
  • Strasbourg, France, 67098
    • Hopital Hautepierre - CHU Strasbourg; Service de Neurologie
• Germany
  • Berlin, Germany, 10117
    • Charité Universitaetsmedizin Berlin, Campus Charité Mitte
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus"; MS Center Dresden
  • Hamburg, Germany, 22291
    • Asklepiosklinik Barmbek; Abteilung Neurologie
  • Hannover, Germany, 30171
    • Diakoniekrankenhaus Henriettenstiftung gGMBH; Klinik für Neurologie und klinische Neurophysiologie
  • Mainz, Germany, 55131
    • Universitaetsklinikum Mainz - PS; Klinik und Poliklinik fuer Neurologie
  • Oldenburg, Germany, 26122
    • Praxis Dr. med. Mathias Niedhammer, Facharzt für Neurologie
  • Prien, Germany, 83209
    • Neurozentrum Prien Elisabeth Hans-Thümmler Stefan Braune
  • Rostock, Germany, 18147
    • Universitätsklinikum Rostock, Zentrum für Nervenheilkunde; Klinik und Poliklinik für Neurologie
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen, Zentrum für Neurologie
  • Westerstede, Germany, 26655
    • Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem AOK; Neurologiai Klinika
  • Budapest, Hungary, 1204
    • Fovarosi Onkormanyzat Jahn Ferenc Del-Pesti
  • Tatabánya, Hungary, 2800
    • Szent Borbala Korhaz; Neurology
• Israel
  • Ramat-Gan, Israel, 5262000
    • Chaim Sheba Medical Center; Neurology Department
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele
  • Valle D?Aosta
    • Gallarate, Valle D?Aosta, Italy, 21013
      • Azienda Socio Sanitaria Territoriale della Valle Olona (pres
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Azienda Ospedaliera di Padova; Clinica Neurologica
• Latvia
  • Riga, Latvia, 1015
    • Maritime Medicine Centre of Latvia Hospital of Vecmilgravis Department of Neurology
  • Riga, Latvia, LV-1002
    • P. Stradins Clinical University Hospital; Neurology
• Lithuania
  • Kaunas, Lithuania, 50009
    • Kaunas Medical University Hospital
  • Klaipeda, Lithuania, 92288
    • Klaipeda University Hospital Public Institution
  • Vilnius, Lithuania, 08661
    • Vilnius University Hospital Santariskiu Clinic
• Mexico
  • Mexico CITY (federal District)
    • Ciudad de México, Mexico CITY (federal District), Mexico, 03600
      • Grupo Médico Camino S.C.
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64460
      • Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León
• Netherlands
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis Nieuwegein
• Peru
  • Callao, Peru, 04
    • Policlinico Especializado en Neurologia
  • Lima, Peru
    • Hospital Nacional Dos de Mayo
  • Lima, Peru, 18
    • Clinica Anglo Americana
  • Pueblo Libre, Peru, Lima 21
    • Clinica Centenario Peruano Japonesa; Neurology
• Poland
  • 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.
  • Katowice, Poland, 40-588
    • Specjal. Praktyka Lekarska; Prof. Grzegorz Opala
  • Plewiska, Poland, 62-064
    • Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych
• Portugal
  • Braga, Portugal, 4710-243
    • Hospital de Braga; Servico de Neurologia
• Russian Federation
  • Kemerovo, Russian Federation, 650066
    • Kemerovo Regional Clinical Hospital
  • Novosibirsk, Russian Federation, 630007
    • FSBIH Siberian Regional Medical Centre of FMBA of Russia
  • Novosibirsk, Russian Federation, 630090
    • MRC for Oncology and Neurology Biotherapy
  • Samara, Russian Federation, 443099
    • Samara State Medical University
  • Smolensk, Russian Federation, 214018
    • Reg. SI of Health Care Smolensk Regional Clinical Hospital
  • Tyumen, Russian Federation, 625000
    • Regional Multiple Sclerosis Centre b/o CC ECM "Neftyanik"
  • Moskovskaja Oblast
    • Moskva, Moskovskaja Oblast, Russian Federation, 107150
      • Central Clinical Hospital #2 N.A. Semashko OAO RJHD
    • Moskva, Moskovskaja Oblast, Russian Federation, 115682
      • FGBU FNKC FMBA of Russia
  • Sankt Petersburg
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 194354
      • St.-Peterburg State institution of health care City multifield hospital #2
    • St.Petersburg, Sankt Petersburg, Russian Federation, 194044
      • MMA of Ministry of Defense of Russia named after S.M. Kirov
  • Sverdlovsk
    • Yekaterinburg, Sverdlovsk, Russian Federation, 620102
      • Sverdlovsk Regional Clinical Hospital 1
  • Tjumen
    • Tyumen, Tjumen, Russian Federation, 625000
      • Regional Multiple Sclerosis Centre b/o CC ECM "Neftyanik"
• Serbia
  • Belgrade, Serbia, 11040
    • Military Medical Academy
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • NIS, Serbia, 18000
    • Clinical Center Nis
• Slovakia
  • Bratislava, Slovakia, 813 69
    • FNsP Bratislava - Nemocnica Stare mesto
  • Bratislava, Slovakia, 826 06
    • FNsP Bratislava, Nemocnica Ruzinov
  • Bratislava, Slovakia, 851 07
    • Univerzitna nemocnica Bratislava Nemocnica sv. Cyrila a Metoda; Nemocnicna lekaren
  • Zilina, Slovakia, 012 07
    • Fakultna nemocnica s poliklinikou Zilina
• South Africa
  • Durban, South Africa, 4319
    • Dr CC Coetzee Inc
• Spain
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Tenerife
    • Santa Cruz De Tenerife, Tenerife, Spain, 38010
      • Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia
  • Vizcaya
    • Bilbao, Vizcaya, Spain, 48013
      • Hospital de Basurto
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik
  • Lugano, Switzerland, 6900
    • Ospedale Regionale Lugano Civico Medizin Neurologie; Neurologia
• Tunisia
  • Mannouba, Tunisia, 2010
    • Hopital Razi
  • Monastir, Tunisia, 5000
    • Hopital Universitaire Fattouma Bourguiba
  • Tunis, Tunisia, 1006
    • Hopital Charles Nicolle
• Ukraine
  • Donetsk, Ukraine, 83099
    • MMPIDon.Reg.Cl.&Ter.Med.Com.Neur.Dept.DNMU n.a.M.Gorkiy; Ch. of Nervous Diseases and Med. Genetics
  • Kharkov, Ukraine, 61068
    • St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis
  • Kyiv, Ukraine, 03110
    • Kyiv City Cl.Hosp.#4 Depart.of Neurology #2NMU; Department of Neurology
  • Lviv, Ukraine, 79010
    • Lviv Regional Clinical Hospital; Department of Neurology
  • Vinnytsya, Ukraine, 21005
    • Vin.Reg.Psych.Hosp.N.A Yuschenko O.I., Vnmu N.A. Pyrogov; Department of Nervous Diseases
• United Kingdom
  • Liverpool, United Kingdom, L9 7LJ
    • Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT
  • London, United Kingdom, E1 1BD
    • Royal London Hospital; Neurology
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • 21st Century Neurology
  • California
    • Carmichael, California, United States, 95608
      • Mercy Medical Group
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Laguna Hills, California, United States, 92653
      • MS Center of California
    • Los Angeles, California, United States, 90027
      • Southern California Permanente Medical Group
    • Pasadena, California, United States, 91105
      • Neuro-Therapeutics Inc.
    • San Francisco, California, United States, 94115
      • University of California at San Francisco
  • Florida
    • Melbourne, Florida, United States, 32901
      • Health First Physicians Inc.
    • Miami, Florida, United States, 33133
      • Mercy Research Institute
    • South Miami, Florida, United States, 33143
      • Miami Research Associates
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • NeuroTrials Research, Inc.
    • Atlanta, Georgia, United States, 30309
      • Shepherd Center Inc.
    • Atlanta, Georgia, United States, 30322
      • Emory University; Department of Neurology
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University; Dept. of Neurology
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology Ltd
  • Indiana
    • Avon, Indiana, United States, 46123
      • American Health Network Institute, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • Michigan
    • Clinton Township, Michigan, United States, 48035
      • Michigan Neurology Associates P.C.
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Institute for Neurological Disorders
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • The Minneapolis Clinic of Neurology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University; Wash Uni. Sch. Of Med
    • Saint Louis, Missouri, United States, 63131
      • The MS Center for Innovations In Care
  • Nebraska
    • Omaha, Nebraska, United States, 68198-0600
      • University of Nebraska Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • North Carolina
    • Advance, North Carolina, United States, 27006
      • The MS Center; Advance Neurology and Pain
    • Charlotte, North Carolina, United States, 28277
      • Onsite Clinical Solutions LLC
    • Charlotte, North Carolina, United States, 28204
      • Atrium Health Neurosciences Institute ? Charlotte
    • Hickory, North Carolina, United States, 28602
      • Neurology Associates PA
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University Neurology Inc.
    • Columbus, Ohio, United States, 43212
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Neurological Specialties
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center; Depatment of Neurosensory sciences
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee-Woman's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Uni of Texas Health Science Center At Houston
    • Lubbock, Texas, United States, 79410
      • Bhupesh Dihenia M.D. P.A.
  • Vermont
    • Burlington, Vermont, United States, 05405
      • Uni of Vermont Medical Center;
  • Washington
    • Tacoma, Washington, United States, 98405
      • Multicare Research Institute; Multicare Neuroscience Center of Washington

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 participants with EDSS 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 (e.g., 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 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	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
Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks	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	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
Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96	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	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)	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
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. 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 108
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 108
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
Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96	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.	From Week 24 up to Week 96
Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab	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
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 588 weeks

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): August 31, 2011
• Primary Completion (Actual): April 2, 2015
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: November 23, 2010
• First Submitted That Met QC Criteria: November 23, 2010
• First Posted (Estimated): November 24, 2010

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 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: WA21092; 2010-020337-99 (EudraCT Number)

Drug and device information, study documents

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