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AzTrials

Relapsing Multiple SclerosisPhase 3NCT01412333

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

A Phase 3 study testing Interferon beta-1a and Ocrelizumab in people with Relapsing Multiple Sclerosis, run by Hoffmann-La Roche at 165 sites in 24 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Relapsing Multiple Sclerosis
What is being tested?
Interferon beta-1a and Ocrelizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
835 participants
Where
165 sitesin 24 countries
Study dates
20 Sep 2011to 30 Dec 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

165 sites in 24 countries.

165 sites in 24 countries

United States48 sites

  • Abington Neurological Associates

    Abington, Pennsylvania, 19001

  • University of Michigan Health System

    Ann Arbor, Michigan, 48109-0666

  • Atlanta Neuroscience Institute

    Atlanta, Georgia, 30327

  • The Neurological Institute PA

    Charlotte, North Carolina, 28204

  • Columbus Neuroscience

    Columbus, Ohio, 43801

  • Neurology Clinic PC

    Cordova, Tennessee, 38018

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390-0001

  • University of Colorado

    Denver, Colorado, 80262

  • Wayne State University; Department of Neurology

    Detroit, Michigan, 48201

  • Associated Neurologists of Southern CT PC

    Fairfield, Connecticut, 06824

  • Advanced Neurosciences Research LLC

    Fort Collins, Colorado, 80528

  • The Minneapolis Clinic of Neurology

    Golden Valley, Minnesota, 55422

  • Absher Neurology PA

    Greenville, South Carolina, 29607

  • Neurology Associates PA

    Hickory, North Carolina, 28602

  • Infinity Clinical Research

    Hollywood, Florida, 33024

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Josephson Wallack Munshower Neurology PC

    Indianapolis, Indiana, 46256

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Sibyl Wray MD Neurology PC

    Knoxville, Tennessee, 37934

  • Empire Neurology, PC

    Latham, New York, 12210

  • Associates in Neurology PSC

    Lexington, Kentucky, 40513

  • Collaborative Neuroscience Research, LLC

    Long Beach, California, 90806

  • Bhupesh Dihenia M.D. P.A.

    Lubbock, Texas, 79410

  • University of Miami; Dept. of Neurology MS Center

    Miami, Florida, 33136

  • Advanced Neurosciences Institute

    Nashville, Tennessee, 37205

  • Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr

    New York, New York, 63110

  • Rutgers New Jersey Medical School

    Newark, New Jersey, 07103

  • Neurological Services of Orlando

    Orlando, Florida, 32806

  • Stanford University Medical Center

    Palo Alto, California, 94304

  • South Shore Neurologic Associates P.C.

    Patchogue, New York, 11772

  • Hope Research Institute

    Phoenix, Arizona, 85050

  • MidAmerica Neuroscience Institute

    Prairie Village, Kansas, 66206

  • Raleigh Neurology Associates

    Raleigh, North Carolina, 27607-6520

  • University of Rochester Medical Center

    Rochester, New York, 14642

  • Central Texas Neurology Consultants

    Round Rock, Texas, 78681

  • Integra Clinical Research, Llc

    San Antonio, Texas, 78229

  • Neurology Center of San Antonio

    San Antonio, Texas, 78258

  • Lovelace Scientific Resources

    Sarasota, Florida, 34292

  • HonorHealth Neurology

    Scottsdale, Arizona, 85251

  • Swedish Neuroscience Institute

    Seattle, Washington, 98122

  • SUNY at Stony Brook

    Stony Brook, New York, 11790

  • University of South Florida

    Tampa, Florida, 33612

  • Holy Name Hospital

    Teaneck, New Jersey, 07666

  • MS Comprehensive Care Center

    Teaneck, New Jersey, 07666

  • Shore Neurology

    Toms River, New Jersey, 08755

  • Territory Neurology and Research Institute

    Tucson, Arizona, 85704

  • Dragonfly Research, LLC

    Wellesley, Massachusetts, 02481

  • University of Massachusetts Memorial Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

Germany10 sites

  • Sankt Gertrauden Krankenhaus; Neurologisches Facharztzentrum

    Berlin, 10713

  • Neurologische Praxis Bonn

    Bonn, 53117

  • Universitätsklinikum Düsseldorf; Klinik für Neurologie

    Düsseldorf, 40225

  • Zentrum fuer ambulante Neurologie

    Essen, 45138

  • Universitaetsklinikum Frankfurt; Klinik für Neurologie

    Frankfurt, 60528

  • Universitaetsklinikum Heidelberg

    Heidelberg, 69120

  • Ratsapotheke Mittweida

    Mittweida, 09648

  • Klinikum Grosshadern der LMU

    München, 81377

  • Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum

    München, 81675

  • Neurologische Gemeinschaftspraxis Dr. Lang, Prof. Schreiber, Dr. Krauß, Dr. Kornhuber

    Ulm, 89073

Other trials in Germany

Italy10 sites

  • Ospedale Generale Regionale F. Miulli

    Acquaviva delle Fonti, Apulia, 70021

  • Fond. Ist. S. Raffaele - giglio

    Cefalù, Sicily, 90015

  • A.O. Universitaria S. Martino Di Genova

    Genoa, Liguria, 16132

  • Fondazione IRCCS Istituto Neurologico Carlo Besta; Farmacia Interna

    Milan, Lombardy, 20133

  • Ospedale Civile di Montichiari; Centro Sclerosi Multipla

    Montichiari, Lombardy, 25018

  • Ospedale degli Infermi

    Ponderano, Piedmont, 13875

  • Azienda Ospedaliera Universitaria Policlinico Tor Vergata

    Rome, Lazio, 00133

  • Policlinico Universitario Agostino Gemelli

    Rome, Lazio, 00168

  • Ospedale Casa Sollievo Della Sofferenza IRCCS

    San Giovanni Rotondo, Apulia, 71013

  • Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona

    Torrette - Ancona, The Marches, 60100

Other trials in Italy

Spain10 sites

  • Hospital General Univ. de Alicante

    Alicante, 03010

  • Institut Catala d?Oncologia Hospital Germans Trias i Pujol

    Badalona, Barcelona, 08916

  • Hospital del Mar

    Barcelona, 08003

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitari de Girona Dr Josep Trueta

    Girona, 17007

  • Hospital Universitari de Bellvitge; Servicio de Neurologia

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Hospital General Universitario Gregorio Marañon; Servicio de Neurologia

    Madrid, 28007

  • Hospital Universitario Clinico San Carlos

    Madrid, 28040

  • Hospital Regional Universitario de Malaga

    Málaga, 29010

  • Hospital Clinico Universitario de Valencia; Servicio de Neurologia

    Valencia, 46010

Other trials in Spain

Poland9 sites

  • Vitamed

    Bydgoszcz, 85-021

  • MA-LEK Clinical Sp. Z o.o.

    Katowice, 40-595

  • Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K

    Krakow, 31-505

  • SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM;Oddzial Kliniczny Neurologii

    Lodz, 90-153

  • Centrum Neurologii Krzysztof Selmaj

    Lodz, 90-324

  • Samodz.Publi.Szpital Kliniczny; nr 4 w Lublinie

    Lublin, 20-954

  • Wojewodzki Specjalistyczny Szpital w Olsztynie; Oddzial Neurologiczny z Pododdzialem Udarowym

    Olsztyn, 10-561

  • Neuro-Care Gabriela Klodowska

    Siemianowice ?l?skie, 41-100

  • mMED Maciej Czarnecki

    Warsaw, 01-684

Other trials in Poland

Canada8 sites

  • Multiple Sclerosis Clinic

    Calgary, Alberta, T2N 2T9

  • University of Alberta; Northern Alberta Trials & Research Centre

    Edmonton, Alberta, T6G 2C8

  • Clinique NeuroOutaouais

    Gatineau, Quebec, J8Y 1W2

  • Recherche Sepmus Inc.

    Greenfield Park, Quebec, J4V 2J2

  • Hôpital Maisonneuve - Rosemont; Recherche Clinique de Neurologie

    Montreal, Quebec, H1T 2M4

  • Montreal Neurological Institute and Hospital

    Montreal, Quebec, H3A 2B4

  • The Ottawa Hospital - General Campus

    Ottawa, Ontario, K1H 8L6

  • Vancouver Hospital - UBC Hospital Site

    Vancouver, British Columbia, V6Z 1Y6

Other trials in Canada

Russia8 sites

  • State institution of health care - Territorial Clinical Hospital

    Barnaul, Altayskiy Kray, 656024

  • State autonomous institution of healthcare Inter-regional clinical and diagnostic center

    Kazan', Tatarstan Republic, 420101

  • Kirov City Clinical Hospital #1; Neurology Department

    Kirov, 610014

  • SBHI of Nizhny Novgorod region City Clinical Hospital #3; neurology department

    Nizniy Novgorod, 603155

  • Perm SMA n.a. academ. E.A. Vagner

    Perm, 614990

  • City Clinical Hospital#2

    Pyatigorsk, Stavropol Kray, 357538

  • St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta

    Saint Petersburg, Sankt-Peterburg, 197022

  • Saratov State Medical University of RosZdrav; Neurology

    Saratov, 410012

Other trials in Russia

Turkey (Türkiye)8 sites

  • Hacettepe University Medical Faculty; Neurology

    Ankara, 06100

  • Haseki Training and Research Hospital

    Istanbul, 34096

  • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali

    Istanbul, 34098

  • Istanbul Bilim Universty Medical Fac.

    Istanbul, 34394

  • Ege University Medical Faculty

    Izmir, 35100

  • Kocaeli University Medical Faculty

    Kocaeli, 41380

  • Ondokuz Mayis Univ. Med. Fac.; Neurology

    Samsun, 55139

  • Karadeniz Tecnical Uni. Med. Fac.; Neurology

    Trabzon, 61080

Other trials in Turkey (Türkiye)

France6 sites

  • Hopital Neurologique Pierre Wertheimer

    Bron, 69500

  • Hôpital General - Service de neurologie; Service de neurologie

    Dijon, 21079

  • Hôpital Saint Philibert

    Lommé, 59462

  • Groupe Hospitalier Pitie-Salpetriere

    Paris, 75651

  • Hôpital Maison Blanche; Service de Neurologie

    Reims, 51092

  • CHU toulouse - Hôpital Purpan; Departement de Neurologie

    Toulouse, 31059

Other trials in France

Mexico6 sites

  • Instituto Biomedico De Investigacion A.C.

    Aguascalientes, 20127

  • Hospital CIMA Chihuahua; Centro de Investigación Clínicatorre de Consultoriospiso 4

    Chihuahua City, 31238

  • Hospital Angeles Culiacan; Neurociencias

    Culiacán, Sinaloa, 80020

  • Hospital Mexico Americano SC; Departamento de Electroencefalografía

    Guadalajara, Jalisco, 44620

  • Mexico Centre for Clinical Research

    Mexico City, Mexico CITY (federal District), 03100

  • Clinical Research Institute

    Tlalnepantla, Mexico CITY (federal District), 54055

Other trials in Mexico

Ukraine5 sites

  • Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?; Neurology Department

    Chernihiv, 14029

  • City Clinical Hospital #4

    Dnipropetrovsk, 49102

  • State Institution V.K. Gusak Institute of Urgent and Recover; Dep of Reconstructive Angioneurology a

    Donetsk, 83045

  • Road Clinical Hospital of Donetsk Station; Neurology Department

    Donetsk, 83114

  • Regional Clinical Hospital; Neurology Department

    Ivano-Frankivsk, 76008

Other trials in Ukraine

Belarus4 sites

  • Grodno State Medical University

    Hrodna, Grodnenskaya, 230017

  • City Clinical Hospital #9

    Minsk, 220116

  • Vitebsk; Regional Diagnostic Center

    Vitebsk, Vitebsk Oblast, 210023

  • Vitebsk Regional Clinical Hospital

    Vitebsk, Vitebsk Oblast, 210037

Other trials in Belarus

Bulgaria4 sites

  • MHATNP Sv.Naum EAD; Clinic for intensive treatment of neurology diseases

    Sofia, 1113

  • Fifth MHAT-Sofia AD; Neuro Dept with Vascular Unit

    Sofia, 1233

  • MHAT National Cardiology Hospital, EAD; Neurology

    Sofia, 1309

  • UMHAT Alexandrovska, EAD; Neurology

    Sofia, 1431

Other trials in Bulgaria

Croatia4 sites

  • General Hospital Pula

    Pula, 52100

  • General Hospital Varazdin

    Varaždin, 42000

  • Clinical Hospital Centre Zagreb;Clinic for Neurology

    Zagreb, 10000

  • Uni Hospital Centre Dubrava

    Zagreb, 10000

Other trials in Croatia

Czechia4 sites

  • Fakultni nemocnice Brno

    Brno, 613 00

  • Neurospol s.r.o.

    Havířov, 736 00

  • Pardubicka Krajska Nemocnice; Department of Neurology

    Pardubice, 532 03

  • Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni

    Teplice, 415 29

Other trials in Czechia

Sweden4 sites

  • Sahlgrenska Sjukhuset; Neurology

    Gothenburg, 413 45

  • Karolinska Universitetssjukhuset Solna Neurology

    Stockholm, 113 41

  • Karolinska Universitetssjukhuset Huddinge

    Stockholm, 171 64

  • Norrlands Universitetssjukhus

    Umeå, 901 85

Other trials in Sweden

United Kingdom4 sites

  • Royal Devon and Exeter Hospital (Wonford)

    Exeter, EX2 5DW

  • Kings College Hospital; Neurosciences Clinical Trials Office

    London, SE5 9NT

  • City General Hospital; Department of Neurology

    Stoke-on-Trent, ST4 6QG

  • Morriston Hospital

    Swansea, SA6 6NL

Other trials in United Kingdom

Brazil3 sites

  • Santa Casa de Misericordia; de Belo Horizonte

    Belo Horizonte, Minas Gerais, 30150-221

  • Hospital das Clinicas - UNICAMP

    Campinas, São Paulo, 13083-887

  • Hospital Universitario Gaffree e Guinle

    Rio de Janeiro, Rio de Janeiro, 20270-004

Other trials in Brazil

Slovakia3 sites

  • MUDr. Beata Dupejova Neurologicka ambulancia s.r.o

    Banská Bystrica, 974 04

  • Fakultna Nemocnica Roosevelta

    Banská Bystrica, 975 17

  • Vseobecna nemocnica s poliklinikou Levoca a.s.

    Levoča, 054 01

Other trials in Slovakia

Argentina2 sites

  • ALPI-Inst. de Rehabilitacion Marcelo Fitte

    Buenos Aires, C1425BWO

  • STAT Research S.A.

    Ciudad de Buenos Airesa, C1013AAB

Other trials in Argentina

Bosnia and Herzegovina2 sites

  • University Clinic Ctr Sarajevo

    Sarajevo, 71 000

  • Uni Hospital Center Tuzla

    Tuzla, 75000

Other trials in Bosnia and Herzegovina

Belgium1 site

  • UZ Antwerpen

    Edegem, 2650

Other trials in Belgium

Ireland1 site

  • St Vincents University Hospital

    Dublin

Other trials in Ireland

Norway1 site

  • Haukeland Universitetssykehus

    Bergen, 5053

Other trials in Norway

About this study

Official title: 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).

Being tested
Interferon beta-1a, Ocrelizumab-matching placebo, Ocrelizumab, Interferon beta-1a-matching placebo

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Interferon beta-1aDrug

    Also called Rebif

  • Ocrelizumab-matching placeboDrug

  • OcrelizumabDrug

    Also called RO4964913

  • Interferon beta-1a-matching placeboDrug

Study groups in NCT01412333
Study groupRoleWhat they receive
Interferon beta-1a 44 mcg SCActive comparatorInterferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks).
Receives: Drug: Interferon beta-1a; Drug: Ocrelizumab-matching placebo
OcrelizumabExperimentalOcrelizumab 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.
Receives: Drug: Ocrelizumab; Drug: Interferon beta-1a-matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Week 96

Secondary outcomes (13)

  1. 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.

    Measured: Week 104

  2. 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.

    Measured: Baseline up to week 96

  3. 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.

    Measured: Baseline up to week 96

  4. 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.

    Measured: Week 96

  5. 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.

    Measured: Week 104

  6. 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.

    Measured: Baseline up to week 96

  7. 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.

    Measured: Baseline, Week 96

  8. 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).

    Measured: From week 24 up to week 96

  9. 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.

    Measured: Baseline, Week 96

  10. 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.

    Measured: Week 96

  11. 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.

    Measured: Baseline up to Week 96

  12. 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.

    Measured: Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96

  13. 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.

    Measured: Baseline up to Week 96

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2011 (estimated)
  2. Study start20 Sep 2011
  3. Primary completion12 May 2015
  4. Study completion30 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
835 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01412333
Sponsor's protocol ID
WA21093
Other IDs
2010-020315-36
Status last verified
Mar 2024
First submitted
8 Aug 2011
Last updated
8 Mar 2024
Data monitoring committee
Yes

Publications

  • Hauser SL, Bar-Or A, Giovannoni G, Montalban X, Lebrun-Frenay C, Amezcua L, Villar LM, Arnold DL, Weber MS, Filippi M, Pasquarelli N, Chognot C, Wang Q, Schneble HM, Craveiro L, Kappos L. Ten Years of Ocrelizumab in Relapsing Multiple Sclerosis: The OPERA I and II Randomized Clinical Trials. JAMA Neurol. 2026 Oct 5. doi: 10.1001/jamaneurol.2026.3507. Online ahead of print.

    PubMed 42832215

  • Kappos L, Yiu S, Reucassel J, Oh J, Granziera C, Killestein J, Bermel RA, Berge C, Kazlauskaite A, Schneble HM, Dahlke F, Cree BAC. Performance of Composite Endpoints Defining Progression Independent of Relapse Activity in Multiple Sclerosis. Ann Clin Transl Neurol. 2025 Sep;12(9):1805-1812. doi: 10.1002/acn3.70111. Epub 2025 Jul 8.

    PubMed 40629721

  • Montobbio N, Bovis F, Signori A, Carmisciano L, Schiavetti I, Ponzano M, Tur C, Granziera C, Cagol A, Arnold DL, Kappos L, Sormani MP. Uncovering a bias in estimated treatment effects on PIRA in multiple sclerosis clinical trials. EBioMedicine. 2025 Jul;117:105802. doi: 10.1016/j.ebiom.2025.105802. Epub 2025 Jun 18.

    PubMed 40554392

  • Kappos L, Yiu S, Dahlke F, Coetzee T, Cutter GR, Yuen S, Bonati U, Lublin FD. Composite Confirmed Disability Worsening/Progression Is a Useful Clinical Endpoint for Multiple Sclerosis Clinical Trials. Neurology. 2025 May 27;104(10):e213558. doi: 10.1212/WNL.0000000000213558. Epub 2025 Apr 21.

    PubMed 40258203

  • Benedict RH, Kappos L, Miller A, Hartung HP, Overell J, Pei J, Dahlke F, Bernasconi C, Koendgen H, Wang Q, Bonati U, Cohan S. Cognitive effects of ocrelizumab vs interferon beta-1a in relapsing multiple sclerosis: A post hoc analysis of the OPERA I/II trials. Mult Scler Relat Disord. 2025 Mar;95:106310. doi: 10.1016/j.msard.2025.106310. Epub 2025 Feb 2.

    PubMed 39965438

  • Muros-Le Rouzic E, Heer Y, Yiu S, Tozzi V, Braune S, van Hovell P, Bergmann A, Bernasconi C, Model F, Craveiro L; NTD study group. Five-year efficacy outcomes of ocrelizumab in relapsing multiple sclerosis: A propensity-matched comparison of the OPERA studies with other disease-modifying therapies in real-world lines of treatments. J Cent Nerv Syst Dis. 2024 Sep 13;16:11795735241260563. doi: 10.1177/11795735241260563. eCollection 2024.

    PubMed 39290861

  • Loomis SJ, Sadhu N, Fisher E, Gafson AR, Huang Y, Yang C, Hughes EE, Marshall E, Herman A, John S, Runz H, Jia X, Bhangale T, Bronson PG. Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials. Sci Rep. 2023 Aug 31;13(1):14313. doi: 10.1038/s41598-023-41099-0.

    PubMed 37652990

  • Kolind S, Gaetano L, Assemlal HE, Bernasconi C, Bonati U, Elliott C, Hagenbuch N, Magon S, Arnold DL, Traboulsee A. Ocrelizumab-treated patients with relapsing multiple sclerosis show volume loss rates similar to healthy aging. Mult Scler. 2023 May;29(6):741-747. doi: 10.1177/13524585231162586. Epub 2023 May 6.

    PubMed 37148240

  • Hauser SL, Bar-Or A, Weber MS, Kletzl H, Gunther A, Manfrini M, Model F, Mercier F, Petry C, Wing Q, Koendgen H, Smith T, Kappos L. Association of Higher Ocrelizumab Exposure With Reduced Disability Progression in Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Feb 15;10(2):e200094. doi: 10.1212/NXI.0000000000200094. Print 2023 Mar.

    PubMed 36792367

  • Falet JR, Durso-Finley J, Nichyporuk B, Schroeter J, Bovis F, Sormani MP, Precup D, Arbel T, Arnold DL. Estimating individual treatment effect on disability progression in multiple sclerosis using deep learning. Nat Commun. 2022 Sep 26;13(1):5645. doi: 10.1038/s41467-022-33269-x.

    PubMed 36163349

  • 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.

    PubMed 35672926

  • 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.

    PubMed 34904871

  • 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.

    PubMed 33724637

  • 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.

    PubMed 32690791

  • 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.

    PubMed 32511687

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Interferon beta-1a and Ocrelizumab in people with Relapsing Multiple Sclerosis, run by Hoffmann-La Roche at 165 sites in 24 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 165 sites in United States, Germany, Italy, Spain, Poland and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks In Double Blind Period (time frame: Week 96). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01412333, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2024.

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