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

Relapsing Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01412333
• Other study ID #: WA21093
• Secondary ID: 2010-020315-36
• Status: Completed
• Phase: Phase 3
• Start date: September 20, 2011
• Est. completion date: December 30, 2022

Study information

• Verified date: March 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 835
• Est. completion date: December 30, 2022
• Est. primary completion date: May 12, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Interferon beta-1a

• Ocrelizumab-matching placebo

• Ocrelizumab

• Interferon beta-1a-matching placebo

Locations

Country	Name	City	State
Argentina	ALPI-Inst. de Rehabilitacion Marcelo Fitte	Buenos Aires
Argentina	STAT Research S.A.	Ciudad de Buenos Airesa
Belarus	Grodno State Medical University	Grodno	Hrodzyenskaya Voblasts'
Belarus	City Clinical Hospital #9	Minsk
Belarus	Vitebsk Regional Clinical Hospital	Vitebsk	Vitsyebskaya Voblasts'
Belarus	Vitebsk; Regional Diagnostic Center	Vitebsk	Vitsyebskaya Voblasts'
Belgium	UZ Antwerpen	Edegem
Bosnia and Herzegovina	University Clinic Ctr Sarajevo	Sarajevo
Bosnia and Herzegovina	Uni Hospital Center Tuzla	Tuzla
Brazil	Santa Casa de Misericordia; de Belo Horizonte	Belo Horizonte	MG
Brazil	Hospital das Clinicas - UNICAMP	Campinas	SP
Brazil	Hospital Universitario Gaffree e Guinle	Rio de Janeiro	RJ
Bulgaria	Fifth MHAT-Sofia AD; Neuro Dept with Vascular Unit	Sofia
Bulgaria	MHAT National Cardiology Hospital, EAD; Neurology	Sofia
Bulgaria	MHATNP Sv.Naum EAD; Clinic for intensive treatment of neurology diseases	Sofia
Bulgaria	UMHAT Alexandrovska, EAD; Neurology	Sofia
Canada	Multiple Sclerosis Clinic	Calgary	Alberta
Canada	University of Alberta; Northern Alberta Trials & Research Centre	Edmonton	Alberta
Canada	Clinique NeuroOutaouais	Gatineau	Quebec
Canada	Recherche Sepmus Inc.	Greenfield Park	Quebec
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	Hôpital Maisonneuve - Rosemont; Recherche Clinique de Neurologie	Montréal	Quebec
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Vancouver Hospital - UBC Hospital Site	Vancouver	British Columbia
Croatia	General Hospital Pula	Pula
Croatia	General Hospital Varazdin	Varazdin
Croatia	Clinical Hospital Centre Zagreb;Clinic for Neurology	Zagreb
Croatia	Uni Hospital Centre Dubrava	Zagreb
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Neurospol s.r.o.	Havirov
Czechia	Pardubicka Krajska Nemocnice; Department of Neurology	Pardubice
Czechia	Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni	Teplice
France	Hopital Neurologique Pierre Wertheimer	Bron
France	Hôpital General - Service de neurologie; Service de neurologie	Dijon Cedex
France	Hôpital Saint Philibert	Lommé
France	Groupe Hospitalier Pitie-Salpetriere	Paris
France	Hôpital Maison Blanche; Service de Neurologie	Reims
France	CHU toulouse - Hôpital Purpan; Departement de Neurologie	Toulouse
Germany	Sankt Gertrauden Krankenhaus; Neurologisches Facharztzentrum	Berlin
Germany	Neurologische Praxis Bonn	Bonn
Germany	Universitätsklinikum Düsseldorf; Klinik für Neurologie	Düsseldorf
Germany	Zentrum fuer ambulante Neurologie	Essen
Germany	Universitaetsklinikum Frankfurt; Klinik für Neurologie	Frankfurt
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Ratsapotheke Mittweida	Mittweida
Germany	Klinikum Grosshadern der LMU	Muenchen
Germany	Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum	München
Germany	Neurologische Gemeinschaftspraxis Dr. Lang, Prof. Schreiber, Dr. Krauß, Dr. Kornhuber	Ulm
Ireland	St Vincents University Hospital	Dublin 4
Italy	Ospedale Generale Regionale F. Miulli	Acquaviva delle Fonti	Puglia
Italy	Fond. Ist. S. Raffaele - giglio	Cefalu	Sicilia
Italy	A.O. Universitaria S. Martino Di Genova	Genova	Liguria
Italy	Fondazione IRCCS Istituto Neurologico Carlo Besta; Farmacia Interna	Milano	Lombardia
Italy	Ospedale Civile di Montichiari; Centro Sclerosi Multipla	Montichiari	Lombardia
Italy	Ospedale degli Infermi	Ponderano	Piemonte
Italy	Azienda Ospedaliera Universitaria Policlinico Tor Vergata	Roma	Lazio
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Italy	Ospedale Casa Sollievo Della Sofferenza IRCCS	San Giovanni Rotondo	Puglia
Italy	Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona	Torrette - Ancona	Marche
Mexico	Instituto Biomedico De Investigacion A.C.	Aguascalientes
Mexico	Hospital CIMA Chihuahua; Centro de Investigación Clínicatorre de Consultoriospiso 4	Chihuahua
Mexico	Mexico Centre for Clinical Research	Ciudad de México	Mexico CITY (federal District)
Mexico	Hospital Angeles Culiacan; Neurociencias	Culiacán Rosales	Sinaloa
Mexico	Hospital Mexico Americano SC; Departamento de Electroencefalografía	Guadalajara	Jalisco
Mexico	Clinical Research Institute	Tlalnepantla de Baz	Mexico CITY (federal District)
Norway	Haukeland Universitetssykehus	Bergen
Poland	Vitamed	Bydgoszcz
Poland	MA-LEK Clinical Sp. Z o.o.	Katowice
Poland	Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii K	Krakow
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM;Oddzial Kliniczny Neurologii	Lodz
Poland	Samodz.Publi.Szpital Kliniczny; nr 4 w Lublinie	Lublin
Poland	Wojewodzki Specjalistyczny Szpital w Olsztynie; Oddzial Neurologiczny z Pododdzialem Udarowym	Olsztyn
Poland	Neuro-Care Gabriela Klodowska	Siemianowice ?l?skie
Poland	mMED Maciej Czarnecki	Warszawa
Russian Federation	State institution of health care - Territorial Clinical Hospital	Barnaul	Altaj
Russian Federation	State autonomous institution of healthcare Inter-regional clinical and diagnostic center	Kazan	Tatarstan
Russian Federation	Kirov City Clinical Hospital #1; Neurology Department	Kirov
Russian Federation	SBHI of Nizhny Novgorod region City Clinical Hospital #3; neurology department	Nizniy Novgorod
Russian Federation	Perm SMA n.a. academ. E.A. Vagner	Perm
Russian Federation	City Clinical Hospital#2	Pyatigorsk	Stavropol
Russian Federation	St. Petersburg State Medical University n.a. I.P. Pavlov; Hematology, transfusiology and transplanta	Sankt-peterburg	Sankt Petersburg
Russian Federation	Saratov State Medical University of RosZdrav; Neurology	Saratov
Slovakia	Fakultna Nemocnica Roosevelta	Banska Bystrica
Slovakia	MUDr. Beata Dupejova Neurologicka ambulancia s.r.o	Banska Bystrica
Slovakia	Vseobecna nemocnica s poliklinikou Levoca a.s.	Levoca
Spain	Hospital General Univ. de Alicante	Alicante
Spain	Institut Catala d?Oncologia Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitari de Girona Dr Josep Trueta	Girona
Spain	Hospital Universitari de Bellvitge; Servicio de Neurologia	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañon; Servicio de Neurologia	Madrid
Spain	Hospital Universitario Clinico San Carlos	Madrid
Spain	Hospital Regional Universitario de Malaga	Malaga
Spain	Hospital Clinico Universitario de Valencia; Servicio de Neurologia	Valencia
Sweden	Sahlgrenska Sjukhuset; Neurology	Göteborg
Sweden	Karolinska Universitetssjukhuset Huddinge	Stockholm
Sweden	Karolinska Universitetssjukhuset Solna Neurology	Stockholm
Sweden	Norrlands Universitetssjukhus	Umeå
Turkey	Hacettepe University Medical Faculty; Neurology	Ankara
Turkey	Haseki Training and Research Hospital	Istanbul
Turkey	Istanbul Bilim Universty Medical Fac.	Istanbul
Turkey	Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali	Istanbul
Turkey	Ege University Medical Faculty	Izmir
Turkey	Kocaeli University Medical Faculty	Kocaeli
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
Turkey	Karadeniz Tecnical Uni. Med. Fac.; Neurology	Trabzon
Ukraine	Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?; Neurology Department	Chernihiv
Ukraine	City Clinical Hospital #4	Dnipropetrovsk
Ukraine	Road Clinical Hospital of Donetsk Station; Neurology Department	Donetsk
Ukraine	State Institution V.K. Gusak Institute of Urgent and Recover; Dep of Reconstructive Angioneurology a	Donetsk
Ukraine	Regional Clinical Hospital; Neurology Department	Ivano-Frankivsk
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter
United Kingdom	Kings College Hospital; Neurosciences Clinical Trials Office	London
United Kingdom	City General Hospital; Department of Neurology	Stoke on Trent
United Kingdom	Morriston Hospital	Swansea
United States	Abington Neurological Associates	Abington	Pennsylvania
United States	University of Michigan Health System	Ann Arbor	Michigan
United States	Atlanta Neuroscience Institute	Atlanta	Georgia
United States	The Neurological Institute PA	Charlotte	North Carolina
United States	Columbus Neuroscience	Columbus	Ohio
United States	Neurology Clinic PC	Cordova	Tennessee
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Colorado	Denver	Colorado
United States	Wayne State University; Department of Neurology	Detroit	Michigan
United States	Associated Neurologists of Southern CT PC	Fairfield	Connecticut
United States	Advanced Neurosciences Research LLC	Fort Collins	Colorado
United States	The Minneapolis Clinic of Neurology	Golden Valley	Minnesota
United States	Absher Neurology PA	Greenville	South Carolina
United States	Neurology Associates PA	Hickory	North Carolina
United States	Infinity Clinical Research	Hollywood	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Josephson Wallack Munshower Neurology PC	Indianapolis	Indiana
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Sibyl Wray MD Neurology PC	Knoxville	Tennessee
United States	Empire Neurology, PC	Latham	New York
United States	Associates in Neurology PSC	Lexington	Kentucky
United States	Collaborative Neuroscience Research, LLC	Long Beach	California
United States	Bhupesh Dihenia M.D. P.A.	Lubbock	Texas
United States	University of Miami; Dept. of Neurology MS Center	Miami	Florida
United States	Advanced Neurosciences Institute	Nashville	Tennessee
United States	Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Neurological Services of Orlando	Orlando	Florida
United States	Stanford University Medical Center	Palo Alto	California
United States	South Shore Neurologic Associates P.C.	Patchogue	New York
United States	Hope Research Institute	Phoenix	Arizona
United States	MidAmerica Neuroscience Institute	Prairie Village	Kansas
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	University of Rochester Medical Center	Rochester	New York
United States	Central Texas Neurology Consultants	Round Rock	Texas
United States	Integra Clinical Research, Llc	San Antonio	Texas
United States	Neurology Center of San Antonio	San Antonio	Texas
United States	Lovelace Scientific Resources	Sarasota	Florida
United States	HonorHealth Neurology	Scottsdale	Arizona
United States	Swedish Neuroscience Institute	Seattle	Washington
United States	SUNY at Stony Brook	Stony Brook	New York
United States	University of South Florida	Tampa	Florida
United States	Holy Name Hospital	Teaneck	New Jersey
United States	MS Comprehensive Care Center	Teaneck	New Jersey
United States	Shore Neurology	Toms River	New Jersey
United States	Territory Neurology and Research Institute	Tucson	Arizona
United States	Dragonfly Research, LLC	Wellesley	Massachusetts
United States	University of Massachusetts Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Belarus,  Belgium,  Bosnia and Herzegovina,  Brazil,  Bulgaria,  Canada,  Croatia,  Czechia,  France,  Germany,  Ireland,  Italy,  Mexico,  Norway,  Poland,  Russian Federation,  Slovakia,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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