Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

Official title:

An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03085810
• Other study ID #: MA30143
• Secondary ID: 2016-002937-31
• Status: Completed
• Phase: Phase 3
• Start date: March 24, 2017
• Est. completion date: April 27, 2023

Study information

• Verified date: October 2023
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a prospective, multicenter, open-label, single-arm, phase 3b study which evaluates effectiveness and safety of ocrelizumab in participants with early stage RRMS. The study will consist of an open-label treatment period of 192 weeks and follow-up period of at least 48 weeks.

The optional shorter infusion substudy will evaluate the safety of a shorter infusion of ocrelizumab in a subgroup of participants with early stage RRMS enrolled in the main MA30143 study. Approximately 700 patients will be enrolled in the substudy, and will receive additional 600 mg ocrelizumab administered in a shorter time frame.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1239
• Est. completion date: April 27, 2023
• Est. primary completion date: April 27, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Have a definite diagnosis of RRMS, as per the revised McDonald 2010 criteria

• Have a length of disease duration, from first documented clinical attack consistent with MS disease of less than or equal to (</=) 3 years

• Within the last 12 months one or more clinically reported relapse(s) or one or more signs of MRI activity

• EDSS of 0.0 to 3.5 inclusive, at screening

• An agreement to use an acceptable birth control method for women of childbearing potential, during the treatment period and for at least 6 months or longer after the last dose of study drug

Exclusion Criteria:

• Secondary progressive multiple sclerosis or history of primary progressive or progressive relapsing MS

• Inability to complete an MRI

• Known presence of other neurological disorders

Exclusions Related to General Health:

• Pregnancy or lactation

• Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug

• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study

• History or currently active primary or secondary immunodeficiency

• Lack of peripheral venous access

• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies

• Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study

• Congestive heart failure (New York Heart Association III or IV functional severity)

• Known active bacterial, viral, fungal, mycobacterial infection or other infection, (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or oral antibiotics 2 weeks prior to screening

• History of malignancy, major opportunistic infections, alcohol or drug abuse, recurrent or chronic infection, and/or coagulation disorders

Exclusions Related to Medications:

• Received any prior approved disease modifying treatment (DMT) with a label for MS, for example, interferons, glatiramer acetate, natalizumab, alemtuzumab, daclizumab, fingolimod, teiflunomide and dimethylfumarate

• Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit

• Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)

• Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic therapies (cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, cladribine, mitoxantrone, laquinimod, total body irradiation, or bone marrow transplantation)

• Treatment with investigational DMT

• Treatment with fampridine/dalfamipridine unless on stable dose for >/=30 days prior to screening

Exclusion related to Shorter Infusion Substudy:

• Any previous serious IRRs experienced with ocrelizumab treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Ocrelizumab
Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.

Locations

Country	Name	City	State
Argentina	Centro de Especialidades Neurológicas y Rehabilitación - CENyR	Buenos Aires
Argentina	Hospital Churruca Visca	Buenos Aires
Argentina	Fundacion Rosarina de Neurorehabilitacion	Rosario
Australia	Box Hill Hospital; Department of Neurology	Box Hill	Victoria
Australia	Brain and Mind Centre	Camperdown	New South Wales
Australia	Austin Hospital; Department of Neurology	Heidelberg	Victoria
Australia	Liverpool Hospital	Liverpool	New South Wales
Australia	Perron Institute for Neurological and Translational Science	Nedlands	Western Australia
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal Melbourne Hospital; Department of Neurology	Parkville	Victoria
Australia	Royal North Shore Hospital; Department of Neurology	St Leonards	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Medizinische Universität Graz; Universitätsklinik für Neurologie	Graz
Austria	Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie	Innsbruck
Austria	Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie	Salzburg
Austria	Medizinische Universität Wien; Univ.Klinik fuer Neurologie	Wien
Belgium	AZ Sint Jan	Brugge
Belgium	UZ Brussel	Brussel
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Antwerpen	Edegem
Belgium	CHU Tivoli	La Louvière
Belgium	CHU Sart-Tilman	Liège
Belgium	Revalidatie en MS Centrum	Overpelt
Brazil	Hospital das Clinicas - UFMG	Belo Horizonte	MG
Brazil	Instituto de Neurologia de Curitiba	Curitiba	PR
Brazil	Hospital Sao Lucas - PUCRS	Porto Alegre	RS
Brazil	Hospital das Clinicas - FMUSP	Sao Paulo	SP
Bulgaria	Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.	Sofia
Bulgaria	Shat Np Sveti Naum; 3Rd Clinic of Neurology	Sofia
Bulgaria	UMHAT Alexandrovska, EAD; Neurology	Sofia
Canada	Clinique NeuroOutaouais	Gatineau	Quebec
Canada	Recherche Sepmus Inc.	Greenfield Park	Quebec
Canada	London Health Sciences Centre Uni Campus	London	Ontario
Canada	Montreal Neurological Institute and Hospital	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Sunnybrook Health Science Centre	Toronto	Ontario
Canada	UBC Hospital; Div of Neurology, Dept of Medicine	Vancouver	British Columbia
Croatia	Clinical Hospital Centre Zagreb	Zagreb
Denmark	Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.	Aalborg
Denmark	Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken	Aarhus N
Denmark	Rigshospitalet; Neurologisk Klinik Glostrup	Glostrup
France	CHU de Besancon Hopital Jean Minjoz; Service de Neurologie	Besançon
France	Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie	Bordeaux
France	Hopital Pierre Wertheimer; Neurologie D	Bron
France	CHU de Caen Hopital Cote de Nacre	Caen
France	CHU Hopital Gabriel Montpied; Service de Neurologie	Clermont Ferrand
France	CH de Gonesse; Neurologie	Gonesse
France	CHU de Grenoble; Neurologie	La Tronche
France	Hopital Gui de Chauliac; Neurologie	Montpellier
France	Hopital Central - CHU de Nancy; Service de Neurologie	Nancy
France	Hôpital Guillaume et René Laënnec; Service Neurologie	Nantes
France	Hôpital Pasteur; Service de Neurologie	Nice
France	CHU de Nîmes Hopital Caremeau; Service de Neurologie	Nimes
France	Hôpital de Poissy; Service neurologie	Poissy
France	Centre Hospitalier Universitaire de Rennes	Rennes
France	CHU de Rouen Hopital; Service de Neurologie	Rouen
France	CHU de Strasbourg	Strasbourg
France	Hopital Foch; Neurologie	Suresnes
France	HIA de Toulon hôpital militaire; Neurologie	Toulon
France	CHU toulouse - Hôpital Purpan; Departement de Neurologie	Toulouse
France	CHRU - Hôpital Bretonneau; Neurologie	Tours
Germany	Praxis Dr.med. Sylvia Menck, Fachärztin für Neurologie und Psychiatrie	Barsinghausen
Germany	Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie	Berlin
Germany	Studienzentrum für Neurologie und Psychiatrie	Böblingen
Germany	St. Josef-Hospital, Klinik für Neurologie	Bochum
Germany	Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften	Dresden
Germany	Universitätsklinikum Düsseldorf; Klinik für Neurologie	Düsseldorf
Germany	NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich	Erbach/Odenwald
Germany	Universitätsklinikum Essen (AöR); Klinik für Neurologie	Essen
Germany	MultipEL Studies - Institut für klinische Studien	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische	Kassel
Germany	Uniklinik Schleswig-Holstein; Neuroimmunologie, Institut für Klinische Chemie + Klinik f. Neurologie	Kiel
Germany	Universitaetsklinikum Marburg; Klinik fuer Neurologie	Marburg
Germany	Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum	München
Germany	Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie	Münster
Germany	Praxis Dr. med. Bergmann	Neuburg
Germany	Asklepios Kliniken Schildautal Seesen; Klinik für Neurologie	Seesen
Germany	Universitätsklinikum Tübingen, Zentrum für Neurologie	Tübingen
Hungary	Budapesti Uzsoki Utcai Kórház	Budapest
Hungary	Jahn Ferenc Dél-Pesti Kórház	Budapest
Hungary	Semmelweis Egyetem AOK; Neurologiai Klinika	Budapest
Hungary	VALEOMED Diagnosztikai Központ	Esztergom
Hungary	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika	Szeged
Italy	AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla	Catania	Sicilia
Italy	A.O.U. Mater Domin; U.O. NEUROLOGIA	Catanzaro	Calabria
Italy	AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)	Firenze	Toscana
Italy	Irccs A.O.U.San Martino Ist; Dinogmi	Genova	Liguria
Italy	Ospedale Misericordia USL9 di Grosseto; U.O. Neurologia	Grosseto	Toscana
Italy	Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari	Milano	Lombardia
Italy	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia
Italy	Ospedale Civile di Montichiari; Centro Sclerosi Multipla	Montichiari	Lombardia
Italy	A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche	Napoli	Campania
Italy	Università degli Studi della Campania Luigi Vanvitelli; Dip. Ass. Integrato Med Int-II Clinica Neur	Napoli	Campania
Italy	AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia	Palermo	Sicilia
Italy	IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla	Pozzilli	Molise
Italy	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio
Italy	Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla	Roma	Lazio
Italy	Ospedale Le Scotte; Clinica Neurologica e Malattie Neurometaboliche	Siena	Toscana
Italy	Ospedale Cattinara; Amb Studio Sclerosi Multipla, Clinica Neurlogica	Trieste	Friuli-Venezia Giulia
Kuwait	Ibn Sina Hospital; Neurology Department	Kuwait
Lebanon	American University of Beirut - Medical Center	Beirut
Mexico	Unidad de investigacion en salud (UIS); Neurociencias	Ciudad de México
Mexico	Neurociencias Estudios Clinicos S.C.	Culiacán	Sinaloa
Mexico	Hospital General de Mexico	Mexico	Tlaxcala
Netherlands	Jeroen Bosch Ziekenhuis	'S Hertogenbosch
Netherlands	VU Medisch Centrum; Afdeling Neurologie	Amsterdam
Netherlands	Groene Hart Ziekenhuis	Gouda
Netherlands	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen
Norway	Akershus universitetssykehus HF; Nevroklinikken S203	Lørenskog
Norway	Stavanger Universitetssykehus, Helse Stavanger HF	Stavanger
Poland	Neurocentrum Bydgoszcz sp. z o.o	Bydgoszcz
Poland	COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny	Gdansk
Poland	Care Clinic	Katowice
Poland	Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.	Krakow
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.	Lublin
Poland	Instytut Psychiatrii i Neurologii II Klinika Neurologiczna	Warszawa
Poland	Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie	Warszawa
Portugal	Hospital Garcia de Orta; Servico de Neurologia	Almada
Portugal	Hospital de Braga; Servico de Neurologia	Braga
Portugal	HUC; Servico de Neurologia	Coimbra
Portugal	Hospital Beatriz Angelo; Servico de Neurologia	Loures
Portugal	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto
Romania	Spitalul Universitar de Urgenta Bucuresti	Bucharest
Romania	Spitalul Clinic Judetean Sibiu	Sibiu
Romania	Spitalul Clinic Judetean de Urgenta Mures	Targu-Mures
Slovakia	Univerzitna nemocnica Bratislava - Nemocnica Ruzinov; Neurologicka klinika SZU a UNB	Bratislava
Slovakia	Univerzitna nemocnica Bratislava, Nemocnica Staré Mesto; I. Neurologická klinika SZU a UNB	Bratislava
Slovakia	GB NeuroPRAKTIK, s.r.o	Nitra
Slovakia	Fakultna nemocnica Trnava	Trnava
Slovenia	University Medical Centre; Neurology	Ljubljana
Slovenia	University Medical Centre Maribor	Maribor
Spain	Hospital General Universitario de Alicante; Servicio de Neurología	Alicante
Spain	Hospital de Cruces; Servicio de Neurologia	Barakaldo	Vizcaya
Spain	Hospital del Mar; Servicio de Neurologia	Barcelona
Spain	Hospital Vall d'Hebron; Servicio de Neurología	Barcelona
Spain	Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología	Madrid
Spain	Hospital General Universitario Morales Meseguer; Servicio de Neurología	Murcia
Spain	Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia	Santa Cruz De Tenerife	Tenerife
Sweden	Sahlgrenska Sjukhuset; Neurology	Göteborg
Sweden	Centralsjukhuset; Neurologi och rehabiliteringskliniken	Karlstad
Sweden	Centrum för Neurologi	Stockholm
Switzerland	Universitätsspital Basel; Neurologie	Basel
Switzerland	Inselspital Bern Medizin Neurologie; Neurologische Poliklinik	Bern
Switzerland	Ospedale Regionale di Lugano - Civico; Neurologia	Lugano
Switzerland	Luzerner Kantonsspital Luzern Medizin Neurologie	Luzern
Switzerland	Kantonsspital; Neurologische Klinik	St. Gallen
Turkey	Gazi University Medical Faculty; Departmant of Norology	Ankara
Turkey	Hacettepe University Medical Faculty; Neurology	Ankara
Turkey	Mustafa Kemal Ataturk UTF; Department of norology	Hatay
Turkey	Istanbul Bilim Universty Medical Fac.	Istanbul
Turkey	Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali	Istanbul
Turkey	Istanbul University Istanbul Medical Faculty; Neurology	Istanbul
Turkey	Selcuk University Medical Faculty; Norology department	Istanbul
Turkey	Ondokuz Mayis Univ. Med. Fac.; Neurology	Samsun
Turkey	Karadeniz Tecnical Uni. Med. Fac.; Neurology	Trabzon
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Queen Elizabeth University Hospital	Glasgow
United Kingdom	Charing Cross Hospital	London
United Kingdom	King'S College Hospital	London
United Kingdom	National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Royal Victoria Infirmary	Newcastle upon Tyne
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Salford Royal NHS Foundation Trust	Salford
United Kingdom	Abertawe and Bro Morgannwg NHS Trust; Clinical Researdh Institute	Swansea
United States	Shepherd Center Inc.	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	University of Maryland Medical Center; Department of Neurology	Baltimore	Maryland
United States	The NeuroMedical Center	Baton Rouge	Louisiana
United States	Kane Hall Barry Neurology	Bedford	Texas
United States	Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40	Cleveland	Ohio
United States	Neurology Specialists, Inc	Dayton	Ohio
United States	Advanced Neurology of Colorado, LLC	Fort Collins	Colorado
United States	Neurology Center of New England	Foxboro	Massachusetts
United States	Minneapolis Clinic of Neurology	Golden Valley	Minnesota
United States	Neurology Associates PA	Hickory	North Carolina
United States	University of California Irvine	Irvine	California
United States	Cleveland Clinic Lou Ruvo; Center for Brain Research	Las Vegas	Nevada
United States	Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	College Park Family Care Ctr	Overland Park	Kansas
United States	Island Neurological Associates, P.C.	Plainview	New York
United States	Maine Medical Center	Scarborough	Maine
United States	KI Health Partners, LLC; New England Institute for Clinical Research	Stamford	Connecticut
United States	Palo Alto Medical Foundation Research Center	Sunnyvale	California
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington
United States	University of South Florida - Bradenton	Tampa	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Dragonfly Research, LLC	Wellesley	Massachusetts
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Bulgaria,  Canada,  Croatia,  Denmark,  France,  Germany,  Hungary,  Italy,  Kuwait,  Lebanon,  Mexico,  Netherlands,  Norway,  Poland,  Portugal,  Romania,  Slovakia,  Slovenia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS)		Baseline up to 4 years
Primary	Percentage of Participants With Confirmed Disability Improvement (CDI) at Year 1, As Measured Using EDSS		Year 1
Primary	Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 1, As Measured Using EDSS		Year 1
Primary	Percentage of Participants With CDI at Year 2, As Measured Using EDSS		Year 2
Primary	Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 2, As Measured Using EDSS		Year 2
Primary	Percentage of Participants With CDI at Year 4, As Measured Using EDSS		Year 4
Primary	Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 4, As Measured Using EDSS		Year 4
Primary	Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS		Year 1
Primary	Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS		Year 2
Primary	Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 3, As Measured Using EDSS		Year 3
Primary	Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 4, As Measured Using EDSS		Year 4
Primary	Mean Change From Baseline in EDSS Score at Week 24		Baseline, Week 24
Primary	Mean Change From Baseline in EDSS Score at Week 48		Baseline, Week 48
Primary	Mean Change From Baseline in EDSS Score at Week 72		Baseline, Week 72
Primary	Mean Change From Baseline in EDSS Score at Week 96		Baseline, Week 96
Primary	Mean Change From Baseline in EDSS Score at Week 120		Baseline, Week 120
Primary	Mean Change From Baseline in EDSS Score at Week 144		Baseline, Week 144
Primary	Mean Change From Baseline in EDSS Score at Week 168		Baseline, Week 168
Primary	Mean Change From Baseline in EDSS Score at Week 192		Baseline, Week 192
Primary	Time to First Protocol-Defined Event of Disease Activity	Protocol-defined event of disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis [MS], as determined using EDSS/Functional Systems Score [FSS] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8 (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.	Baseline up to 4 years
Primary	Time to First Relapse	Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.	Baseline up to 4 years
Primary	Annualized Relapse Rate	Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.	Baseline up to 4 years
Primary	Proportion of Participants with Infusion Related Reactions (IRRs) Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy		From Week 24 through Week 192
Secondary	Percentage of Participants Who Are Relapse Free	Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.	Weeks 48, 96, 144, 192
Secondary	Percentage of Participants With No Evidence of Protocol Defined Disease Activity	Protocol-defined disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis [MS], as determined using EDSS/Functional Systems Score [FSS] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8. (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.	Weeks 96, 144, 192
Secondary	Percentage of Participants With no Evidence of Progression (NEP)	NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20 percent [%] increase from baseline in timed 25 Foot Walk Test [T25FWT]; 20% increase from baseline in timed 9 hole peg test [9HPT]). CDP will be assessed using EDSS.	Weeks 96, 192
Secondary	Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD)	NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion. CDP will be assessed using EDSS. Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.	Weeks 96, 192
Secondary	Change from Baseline in Multiple Sclerosis Functional Composite (MSFC) Total Score		Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Secondary	Change from Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score		Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Secondary	Change from Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score		Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Secondary	Change from Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score		Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Secondary	Change from baseline in cognitive performance as measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)		Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Secondary	Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI		Baseline, Weeks 8, 24, 48, 96, 144, 192
Secondary	Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI		Baseline, Weeks 8, 24, 48, 96, 144, 192
Secondary	Change from baseline in total T1 hypointense lesion volume as Detected by Brain MRI		Baseline, Weeks 8, 24, 48, 96, 144, 192
Secondary	Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI		Baseline, Weeks 8, 24, 48, 96, 144, 192
Secondary	Change From Baseline in Brain Volume as Detected by Brain MRI		Baseline, Weeks 8, 24, 48, 96, 144, 192
Secondary	Time to Treatment Discontinuation		Baseline up to 4 years
Secondary	Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score		Baseline, Weeks 24, 48, 96, 120, 144, 192
Secondary	SymptoMScreen Composite Score		Baseline, Weeks 24, 48, 96, 120, 144, 192
Secondary	Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score		Baseline, Weeks 24, 48, 96, 120, 144, 192
Secondary	Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Short term safety related to the infusion (infusion-related reactions [IRRs], during infusion and up to 24h after) the overall safety is measured continuously at clinical visits and including every 8 week telephone visits up to 48 weeks post study.	Baseline up to 4 years
Secondary	Proportion of Participants with IRR (overall) in the Shorter Infusion Substudy		From Week 24 through Week 192
Secondary	Proportion of Participants with IRR By Dose at Randomization in the Shorter Infusion Substudy		From Week 24 through Week 192
Secondary	Proportion of Participants with IRRs Leading to Treatment Discontinuation in the Shorter Infusion Substudy		From Week 24 through Week 192