Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)
Multiple Sclerosis, Relapsing-Remitting
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting
Eligibility Criteria
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
Sites / Locations
- University of California Irvine
- Palo Alto Medical Foundation Research Center
- University of Colorado Denver
- Advanced Neurology of Colorado, LLC
- KI Health Partners, LLC; New England Institute for Clinical Research
- Georgetown University Medical Center
- University of South Florida - Bradenton
- Shepherd Center Inc.
- College Park Family Care Ctr
- The NeuroMedical Center
- Maine Medical Center
- University of Maryland Medical Center; Department of Neurology
- Neurology Center of New England
- Dragonfly Research, LLC
- Minneapolis Clinic of Neurology
- Cleveland Clinic Lou Ruvo; Center for Brain Research
- Columbia University Medical Center
- Island Neurological Associates, P.C.
- Neurology Associates PA
- Wake Forest University Health Sciences
- Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40
- Neurology Specialists, Inc
- Vanderbilt University Medical Center
- Kane Hall Barry Neurology
- MultiCare Health System Institute for Research and Innovation
- Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders
- Centro de Especialidades Neurológicas y Rehabilitación - CENyR
- Hospital Churruca Visca
- Fundacion Rosarina de Neurorehabilitacion
- Brain and Mind Centre
- Liverpool Hospital
- John Hunter Hospital
- Royal North Shore Hospital; Department of Neurology
- Princess Alexandra Hospital
- Box Hill Hospital; Department of Neurology
- Austin Hospital; Department of Neurology
- Royal Melbourne Hospital; Department of Neurology
- Perron Institute for Neurological and Translational Science
- Medizinische Universität Graz; Universitätsklinik für Neurologie
- Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
- Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie
- Medizinische Universität Wien; Univ.Klinik fuer Neurologie
- AZ Sint Jan
- UZ Brussel
- Cliniques Universitaires St-Luc
- UZ Antwerpen
- CHU Tivoli
- CHU Sart-Tilman
- Revalidatie en MS Centrum
- Hospital das Clinicas - UFMG
- Instituto de Neurologia de Curitiba
- Hospital Sao Lucas - PUCRS
- Hospital das Clinicas - FMUSP
- Shat Np Sveti Naum; 3Rd Clinic of Neurology
- Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.
- UMHAT Alexandrovska, EAD; Neurology
- UBC Hospital; Div of Neurology, Dept of Medicine
- London Health Sciences Centre Uni Campus
- Ottawa Hospital Research Institute
- Sunnybrook Health Science Centre
- Clinique NeuroOutaouais
- Recherche Sepmus Inc.
- Montreal Neurological Institute and Hospital
- Clinical Hospital Centre Zagreb
- Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.
- Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken
- Rigshospitalet; Neurologisk Klinik Glostrup
- CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
- Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
- Hopital Pierre Wertheimer; Neurologie D
- CHU de Caen Hopital Cote de Nacre
- CHU Hopital Gabriel Montpied; Service de Neurologie
- CH de Gonesse; Neurologie
- CHU de Grenoble; Neurologie
- Hopital Gui de Chauliac; Neurologie
- Hopital Central - CHU de Nancy; Service de Neurologie
- Hôpital Guillaume et René Laënnec; Service Neurologie
- Hôpital Pasteur; Service de Neurologie
- CHU de Nîmes Hopital Caremeau; Service de Neurologie
- Hôpital de Poissy; Service neurologie
- Centre Hospitalier Universitaire de Rennes
- CHU de Rouen Hopital; Service de Neurologie
- CHU de Strasbourg
- Hopital Foch; Neurologie
- HIA de Toulon hôpital militaire; Neurologie
- CHU toulouse - Hôpital Purpan; Departement de Neurologie
- CHRU - Hôpital Bretonneau; Neurologie
- Praxis Dr.med. Sylvia Menck, Fachärztin für Neurologie und Psychiatrie
- Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
- St. Josef-Hospital, Klinik für Neurologie
- Studienzentrum für Neurologie und Psychiatrie
- Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
- Universitätsklinikum Düsseldorf; Klinik für Neurologie
- NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich
- Universitätsklinikum Essen (AöR); Klinik für Neurologie
- MultipEL Studies - Institut für klinische Studien
- Universitaetsklinikum Heidelberg
- Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische
- Uniklinik Schleswig-Holstein; Neuroimmunologie, Institut für Klinische Chemie + Klinik f. Neurologie
- Universitaetsklinikum Marburg; Klinik fuer Neurologie
- Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
- Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie
- Praxis Dr. med. Bergmann
- Asklepios Kliniken Schildautal Seesen; Klinik für Neurologie
- Universitätsklinikum Tübingen, Zentrum für Neurologie
- Semmelweis Egyetem AOK; Neurologiai Klinika
- Budapesti Uzsoki Utcai Kórház
- Jahn Ferenc Dél-Pesti Kórház
- VALEOMED Diagnosztikai Központ
- Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika
- A.O.U. Mater Domin; U.O. NEUROLOGIA
- A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
- Università degli Studi della Campania Luigi Vanvitelli; Dip. Ass. Integrato Med Int-II Clinica Neur
- Ospedale Cattinara; Amb Studio Sclerosi Multipla, Clinica Neurlogica
- Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
- Azienda Ospedaliera Sant'Andrea; UOC Neurologia
- Irccs A.O.U.San Martino Ist; Dinogmi
- IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
- Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari
- Ospedale Civile di Montichiari; Centro Sclerosi Multipla
- IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla
- AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla
- AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia
- AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)
- Ospedale Misericordia USL9 di Grosseto; U.O. Neurologia
- Ospedale Le Scotte; Clinica Neurologica e Malattie Neurometaboliche
- Ibn Sina Hospital; Neurology Department
- American University of Beirut - Medical Center
- Neurociencias Estudios Clinicos S.C.
- Hospital General de Mexico
- Unidad de investigacion en salud (UIS); Neurociencias
- Jeroen Bosch Ziekenhuis
- VU Medisch Centrum; Afdeling Neurologie
- Groene Hart Ziekenhuis
- Zuyderland Medisch Centrum - Sittard Geleen
- Akershus universitetssykehus HF; Nevroklinikken S203
- Stavanger Universitetssykehus, Helse Stavanger HF
- Neurocentrum Bydgoszcz sp. z o.o
- COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny
- Care Clinic
- Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.
- Centrum Neurologii Krzysztof Selmaj
- Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
- Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
- Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
- Hospital Garcia de Orta; Servico de Neurologia
- Hospital de Braga; Servico de Neurologia
- HUC; Servico de Neurologia
- Hospital Beatriz Angelo; Servico de Neurologia
- Hospital Geral de Santo Antonio; Servico de Neurologia
- Spitalul Universitar de Urgenta Bucuresti
- Spitalul Clinic Judetean Sibiu
- Spitalul Clinic Judetean de Urgenta Mures
- Univerzitna nemocnica Bratislava, Nemocnica Staré Mesto; I. Neurologická klinika SZU a UNB
- Univerzitna nemocnica Bratislava - Nemocnica Ruzinov; Neurologicka klinika SZU a UNB
- GB NeuroPRAKTIK, s.r.o
- Fakultna nemocnica Trnava
- University Medical Centre; Neurology
- University Medical Centre Maribor
- Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia
- Hospital de Cruces; Servicio de Neurologia
- Hospital General Universitario de Alicante; Servicio de Neurología
- Hospital del Mar; Servicio de Neurologia
- Hospital Vall d'Hebron; Servicio de Neurología
- Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
- Hospital General Universitario Morales Meseguer; Servicio de Neurología
- Sahlgrenska Sjukhuset; Neurology
- Centralsjukhuset; Neurologi och rehabiliteringskliniken
- Centrum för Neurologi
- Universitätsspital Basel; Neurologie
- Inselspital Bern Medizin Neurologie; Neurologische Poliklinik
- Ospedale Regionale di Lugano - Civico; Neurologia
- Luzerner Kantonsspital Luzern Medizin Neurologie
- Kantonsspital; Neurologische Klinik
- Hacettepe University Medical Faculty; Neurology
- Gazi University Medical Faculty; Departmant of Norology
- Mustafa Kemal Ataturk UTF; Department of norology
- Istanbul University Istanbul Medical Faculty; Neurology
- Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
- Istanbul Bilim Universty Medical Fac.
- Selcuk University Medical Faculty; Norology department
- Ondokuz Mayis Univ. Med. Fac.; Neurology
- Karadeniz Tecnical Uni. Med. Fac.; Neurology
- Cambridge University Hospitals NHS Foundation Trust
- Queen Elizabeth University Hospital
- Royal Free Hospital
- King'S College Hospital
- Charing Cross Hospital
- National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases
- Royal Victoria Infirmary
- Derriford Hospital
- Salford Royal NHS Foundation Trust
- Abertawe and Bro Morgannwg NHS Trust; Clinical Researdh Institute
Arms of the Study
Arm 1
Arm 2
Arm 3
Experimental
Active Comparator
Experimental
Ocrelizumab
Substudy Group 1
Substudy Group 2
Ocrelizumab will be administered intravenously (IV) as two 300-milligram (mg) infusions (infusion length=2.5 hours) on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period.
At week 24 of the main study, eligible participants will be randomized to receive 600 mg ocrelizumab infused over approximately 3.5 hours every 24 weeks for the remainder of the study duration
At week 24 of the main study, eligible participants will be randomized to receive 600 mg ocrelizumab infused over approximately 2 hours followed by sodium chloride given as a slow infusion over the remaining 1.5 hours to mimic the standard-length infusion (3.5 hour) every 24 weeks for the remainder of the study duration