A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT)

An Open-Label Study To Evaluate the Efficacy and Safety of Ocrelizumab in Patients With Relapsing Multiple Sclerosis Who Have A Suboptimal Response to an Adequate Course of Disease-Modifying Treatment

The purpose of this prospective, multicenter, open-label, efficacy, and safety study is to assess the efficacy and safety of ocrelizumab in participants with Relapsing Remitting Multiple Sclerosis (RRMS) who have had a suboptimal response to an adequate course of a Disease-Modifying Treatment (DMT). The study will consist of a Screening period (up to 4 weeks), an Open-label treatment period (96 weeks; with last dose administered at Week 72), and a Follow-up period of at least 2 years.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Biological: Ocrelizumab

• Study Type: Interventional
• Enrollment (Actual): 681
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Kogarah, New South Wales, New South Wales, Australia, 2217
      • St George Hospital
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Bruxelles, Belgium, 1070
    • Hospital Erasme
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Gent, Belgium, 9000
    • UZ Gent
  • La Louvière, Belgium, 7100
    • CHU Tivoli
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Melsbroek, Belgium, 1820
    • Nationaal MS Centrum
  • Overpelt, Belgium, 3900
    • Revalidatie en MS Centrum
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny; Neurologicka klinika
  • Jihlava, Czechia, 58633
    • Nemocnice Jihlava; NEU-Neurologicke oddeleni
  • Prague, Czechia, 12808
    • VFN Praha Poliklinika Rs Centrum - Budova A
  • Praha, Czechia, 150 06
    • Fakultni nemocnice Motol; Neurologicka klinika
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital, Neurologisk Afd. F, Skleroseklinikken
  • Glostrup, Denmark, 2600
    • Rigshospitalet Glostrup; Neurologisk Klinik
  • Odense C, Denmark, 5000
    • Odense Universitetshospital, Neurologisk Afdeling N
  • Sønderborg, Denmark, 6400
    • Sydjysk Skleroseklinik - Sønderborg
• Estonia
  • Tallinn, Estonia, 10617
    • West Tallinn Central Hospital
  • Tallinn, Estonia, 10138
    • East Tallinn Central Hospital; Neurology Department
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• Finland
  • Tampere, Finland, 33100
    • Terveystalo Tampere
  • Turku, Finland, 20520
    • Mehiläinen Neo Turku
• France
  • Besançon, France, 25030
    • CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
  • Bordeaux, France, 33076
    • Groupe Hospitalier Pellegrin; Service de neurochirurgie B
  • Bron, France, 69677
    • Hopital Neurologique et Neurochirurgical Pierre Wertheimer; Service de Neurologie A
  • Clermont-Ferrand, France, 63003
    • Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B
  • Lille, France
    • Hopital Roger Salengro; Service de Neurologie
  • Marseille, France, 13005
    • CHU de la Timone - Hopital d Adultes; Service de Neurologie
  • Montpellier, France, 34295
    • Hopital Gui de Chauliac; Neurologie
  • Nantes, France, 44805
    • Hôpital Guillaume et René Laënnec; Service Neurologie
  • Nice, France, 06002
    • Hôpital Pasteur; Service de Neurologie
  • Paris, France, 75019
    • Fondation Rothschild; Service de Neurologie
  • Paris, France, 75651
    • Groupe Hospitalier Pitié- Salpétrière; Service Neurologie
  • Reims, France, 51092
    • Hôpital Maison Blanche; Service de Neurologie
  • Strasbourg, France, 67091
    • Hôpitaux Universitaires de Strasbourg - Hôpital Civil
  • Toulouse, France, 31059
    • CHU toulouse - Hôpital Purpan; Departement de Neurologie
  • Tours, France, 37000
    • CHRU - Hôpital Bretonneau; Neurologie
• Germany
  • Augsburg, Germany, 86156
    • Klinikum Augsburg, Neurologische Klinik und klinische Neurophysiologie
  • Berg, Germany, 82335
    • Marianne-Strauß-Klinik; Behandlung Kempfen für Multip Sklero Kranke gemeinnütz GmbH
  • Berlin, Germany, 13347
    • Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
  • Berlin, Germany, 10117
    • Charite - Universitatsmedizin Berlin; Klinik fur Neurologie
  • Berlin, Germany, 12099
    • Praxis Dr. Said Masri
  • Berlin, Germany, 12163
    • Gemeinschaftspraxis Dr.med. Reinhard Ehret/Dr. med Wolfram von Pannwitz
  • Bochum, Germany, 44791
    • St. Josef-Hospital, Klinik für Neurologie
  • Bonn, Germany, 53111
    • Gesundheitszentrum St. Johannes Hospital; Neurolog. Gemeinschaftspraxis Dres. Schmidt, Neudecker etc
  • Buchholz, Germany, 21244
    • PNP Buchholz, Praxis für Neurologie - Psychiatrie, Dres. Dee/Gößling/Hoge
  • Böblingen, Germany, 71034
    • Studienzentrum fur Neurologie und Psychiatrie
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
  • Düsseldorf, Germany, 40211
    • Gemeinschaftspraxis für Neurologie; Dr. Katrin Schulte, Dr. Nils Richter, Dr. Margarete Capito
  • Erbach/Odenwald, Germany, 64711
    • NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich
  • Frankfurt, Germany, 60528
    • Universitaetsklinikum Frankfurt; Klinik für Neurologie
  • Freiburg, Germany, 79106
    • Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie
  • Hamburg, Germany, 22179
    • MultipEL Studies - Institut für klinische Studien
  • Hamburg, Germany, 20246
    • Universiätsklinikum Hamburg-Eppendorf , Multiple Sklerose Tagesklinik u. Ambulanz Neurol. Poliklinik
  • Hamburg, Germany, 22083
    • Neurologische Praxisgemeinschaft Hamburger-Straße; Dres. Müller-Habich/Emrich/Vogt
  • Hannover, Germany, 30171
    • Henriettenstiftung Hannover; Klinik fuer Neurologie und Klinische Neurophysiologie
  • Heidelberg, Germany, 69120
    • Neurologische Klinik, Universitätsklinikum Heidelberg
  • Hennigsdorf, Germany, 16761
    • Oberhavel Kliniken GmbH, Klinik Hennigsdorf, Neurologie
  • Itzehoe, Germany, 25524
    • Neurozentrum am Klosterforst in Itzehoe
  • Kassel, Germany, 34121
    • Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische
  • Leipzig, Germany, 04275
    • PANAKEIA - Arzneimittelforschung Leipzig GmbH
  • Magdeburg, Germany, 39120
    • Universitätsklinikum Magdeburg,Otto-von-Guericke-Universität A.ö.R., Klinik für Neurologie
  • Mainz, Germany, 55131
    • Universitaetsklinikum Mainz - PS; Klinik und Poliklinik fuer Neurologie
  • Marburg, Germany, 35043
    • Universitaetsklinikum Marburg; Klinik fuer Neurologie
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
  • München, Germany, 80804
    • Max-Planck-Institut für Psychiatrie
  • München, Germany, 81377
    • Klinikum Grosshadern der LMU; Neuroimmunologie II
  • Münster, Germany, 48149
    • Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie
  • Neuruppin, Germany, 16816
    • Ruppiner Kliniken, Hochschulklinikum der Medizinischen Hochschule Brandenburg, Klinik für Neurologie
  • Oldenburg in Holstein, Germany, 23758
    • AMEOS Klinikum Oldenburg, Klinik für Neurologie und Neurophysiologie
  • Potsdam, Germany, 14471
    • St. Josefs-Krankenhaus, Klinik für Neurologie
  • Stuttgart, Germany, 70182
    • NeuroConcept AG C/O mind mvz GmbH
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen, Zentrum für Neurologie
  • Ulm, Germany, 89073
    • NeuroPoint, Gesellschaft für vorbeugende Gesundheitspflege mbH
  • Westerstede, Germany, 26655
    • Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz
• Ireland
  • Cork, Ireland
    • Cork University Hospital; Clinical Research Facility
  • Dublin, Ireland, 9
    • Beaumont Hospital
  • Dublin 4, Ireland
    • St Vincents University Hospital
• Italy
  • Abruzzo
    • Chieti, Abruzzo, Italy, 66013
      • Ospedale SS. Annunziata - Clinica Neurologica - Centro Sclerosi Multipla
    • L'Aquila, Abruzzo, Italy, 67100
      • Ospedale San Salvatore; Clinica Neurologica - Centro Sclerosi Multipla
  • Campania
    • Napoli, Campania, Italy, 80131
      • A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
    • Napoli, Campania, Italy, 80131
      • Università degli Studi della Campania Luigi Vanvitelli; Dip. Ass. Integrato Med Int-II Clinica Neur
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40139
      • Ospedale Bellaria; Istituto delle Scienze Neurologiche - UO RIABILITAZIONE SCLEROSI MULTIPLA
  • Lazio
    • Roma, Lazio, Italy, 00133
      • Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea; UOC Neurologia
    • Roma, Lazio, Italy, 00168
      • Policlinico Universitario A. Gemelli; UOC Neurologia - Centro Sclerosi Multipla
    • Roma, Lazio, Italy, 00152
      • Ospedale S.Camillo Forlanini; UOSD Day Hospital Neurologico e Neurochirurgico
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Irccs A.O.U.San Martino Ist; Dinogmi
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla
    • Gallarate, Lombardia, Italy, 21013
      • Ospedale S.Antonio Abate; Neurologia 2 - Sclerosi Multipla e Recupero Neurologico
    • Milano, Lombardia, Italy, 20133
      • Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
    • Milano, Lombardia, Italy, 20122
      • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico; UOSD Malattie Neurodegenerative
    • Montichiari, Lombardia, Italy, 25018
      • Ospedale Civile di Montichiari; Centro Sclerosi Multipla
    • Pavia, Lombardia, Italy, 27100
      • IRCCS Istituto Neurologico C. Mondino-Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
  • Marche
    • Ancona, Marche, Italy, 60100
      • AOU Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi; SOD Clinica Neurologica-Am.Sclerosi Multipla
  • Molise
    • Pozzilli, Molise, Italy, 86077
      • IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla
  • Puglia
    • Barletta, Puglia, Italy, 70051
      • Ospedale Dimiccoli Barletta; Dipartimento Testa-Collo - UO Neurologia
    • San Giovanni Rotondo, Puglia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo Della Sofferenza; SC Neurologia
  • Sardegna
    • Cagliari, Sardegna, Italy, 09126
      • Ospedale Binaghi; Centro Sclerosi Multipla
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla
    • Cefalù, Sicilia, Italy, 90015
      • Fondazione Istituto S. Raffaele - Giglio; UO Neurologia
    • Palermo, Sicilia, Italy, 90146
      • AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia
    • Palermo, Sicilia, Italy, 90129
      • AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • AOUC Azienda Ospedaliero-Universitaria Careggi; Neurologia 2
    • Firenze, Toscana, Italy, 50134
      • AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)
    • Siena, Toscana, Italy, 53100
      • AOU Senese - Presidio Ospedaliero Le Scotte; UOSA Neurologia Sperimentale
  • Umbria
    • Perugia, Umbria, Italy, 06156
      • AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica
  • Veneto
    • Padova, Veneto, Italy, 35128
      • Azienda Ospedaliera di Padova; Clinica Neurologica
    • Verona, Veneto, Italy, 37134
      • Policlinico G.B. Rossi; Dip. Scienze Neurologiche Biomediche - Neurologia B - Amb. Sclerosi Multipla
• Netherlands
  • Breda, Netherlands, 4819 EV
    • Amphia Ziekenhuis
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis Nieuwegein
  • Rotterdam, Netherlands, 3079 DZ
    • Maasstadziekenhuis
  • Sittard-Geleen, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum - Sittard Geleen
  • Tilburg, Netherlands, 5042 AD
    • Sint Elizabeth Ziekenhuis
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssykehus
  • Drammen, Norway, 3004
    • Sykehuset Buskerud HF; Nevrologisk avdeling
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Neurologia
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron; Servicio de Neurología
  • Cadiz, Spain, 11009
    • Hospital Puerta del Mar; Sevicio de Neurologia
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre; Servicio de Neurologia
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz; Servicio de Neurologia
  • Madrid, Spain, 28006
    • Universitario de La Princesa; Servicio de Neurología
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos; Servicio de Neurología
  • Murcia, Spain
    • Hospital Universitario Virgen de Arrixaca; Servicio de Neurología
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Valencia, Spain, 46026
    • Hospital Universitario la Fe; Servicio de Neurologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia; Servicio de Neurologia
  • Asturias
    • Oviedo, Asturias, Spain
      • Hospital Universitario Central de Asturias; Servicio de Neurología
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge; Servicio de Neurologia
  • Castellon
    • Castelló de la Plana, Castellon, Spain, 12004
      • Hospital General de Castellon; Servicio de Neurología
  • Girona
    • Salt, Girona, Spain, 17190
      • Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Neurologia
  • LA Coruña
    • Coruña, LA Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia
  • Lerida
    • Lleida, Lerida, Spain, 25198
      • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Neurología
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Hospital Quiron de Madrid; Servicio de Neurologia
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36312
      • Complejo Hospitalario Universitario de Vigo - Xeral Cies; Servicio de Neurologia
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Sjukhuset; Neurology
  • Jönköping, Sweden, 55185
    • Länssjukhuset Ryhov; Medicinkliniken / Neurologmottagningen
  • Stockholm, Sweden, 113 41
    • Centrum för Neurologi
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik
  • Lausanne, Switzerland, 1011
    • CHUV Lausanne Méd.Neurologie
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty; Neurology
  • Istanbul, Turkey, 34093
    • Istanbul Uni Istanbul Medical Faculty
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
  • Izmir, Turkey, 35100
    • Ege University Medical Faculty
  • Kocaeli, Turkey, 41380
    • Kocaeli University Hospital; Department of Neurology
  • Mersin, Turkey, 33079
    • Mersin University Medical Faculty; Neurology
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Univ. Med. Fac.; Neurology
  • Trabzon, Turkey, 61080
    • Karadeniz Tecnical Uni. Med. Fac.; Neurology
• United Kingdom
  • Birmingham, United Kingdom, B15 2WB
    • New Queen Elizabeth Hospital Birmingham
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter Hospital (Wonford)
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • Inverness, United Kingdom, IV2 3UV
    • Raigmore Hospital
  • Leeds, United Kingdom, LS9 7AU
    • Leeds Teaching Hospitals NHS Trust
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, E1 1FR
    • The Royal London Hospital
  • London, United Kingdom, SW9 8RR
    • Kings College Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospita
  • Swansea, United Kingdom, SA6 6NL
    • Morriston Hospital
  • Truro, United Kingdom, TR1 3LQ
    • Royal Cornwall Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have a definite diagnosis of RRMS, confirmed as per the revised McDonald 2010 criteria
• Have a length of disease duration, from first symptom, of less than (<) 10 years
• Have received no more than two prior DMTs, and the discontinuation of the most recent DMT was due to lack of efficacy
• Suboptimal disease control while on a DMT
• Expanded Disability Status Scale (EDSS) of 0.0 to 4.0, inclusive, at Screening
• For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months after the last dose of study drug

Exclusion Criteria:

• Secondary progressive multiple sclerosis (SPMS) or history of primary progressive or progressive relapsing multiple sclerosis (MS)
• Inability to complete an Magnetic Resonance Imaging (MRI) procedure
• Known presence of other neurological disorders
• 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
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• History of opportunistic infections
• History or known presence of recurrent or chronic infection
• History of malignancy
• Congestive heart failure
• Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ocrelizumab; Ocrelizumab will be administered as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.	Biological: Ocrelizumab; Ocrelizumab will be administered as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.; Other Names: RO4964913

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period	A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse (PDR); 24-week CDP based on increase in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan	Week 96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks Period	A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse (PDR); 24-week CDP based on increase in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan	Baseline up to 24 weeks
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks Period	A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse (PDR); 24-week CDP based on increase in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan	Baseline up to 48 weeks
Time to First Protocol-Defined Event of Disease Activity	The definition of a protocol-defined event of disease activity is the occurrence of at least one of the following while on treatment with ocrelizumab: A protocol-defined relapse defined as: Symptoms must persist for >24 hours and should not be attributable to confounding clinical factors; Symptoms should be preceded by neurological stability for at least 30 days; Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment; 24 weeks confirmed disability progression based on increases in EDSS while on treatment with ocrelizumab; A T1 Gd-enhanced lesion after Week 8; A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan.	Baseline up to 96 Weeks
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS)	The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.	Baseline, Weeks: 24, 48, 72, 96
Absolute Change From Baseline in EDSS Category at Week 96	The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.	Up to Week 96
Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at Week 96	The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.	Week 96
Annualized Protocol-defined Relapse Rate at Week 96		Week 96
Time to Onset of 24-week Confirmed Disability Progression		Baseline up to 96 Weeks
Time to Onset of First Protocol-Defined Relapse	A protocol-defined multiple sclerosis (MS) relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms must persist for >24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms should be preceded by neurological stability for at least 30 days; Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment, consistent with an increase of at least:≥ 0.5 points on EDSS scaleor ≥ 2 points on one of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visualor ≥ 1 point on two or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual	Baseline up to 96 Weeks
Time to Onset of First New and/or Enlarging T2 Lesion		Baseline up to 96 Weeks
Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96	Mean number of T1 Gd-enhancing lesions per MRI scan: Total number of T1 Gd-enhanced lesions divided by the total number of interpretable MRI scans	Weeks: 24, 48, 96
Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From		Baseline, Week 96
Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI		Baseline, Week 96
Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96	The number of new and/or enlarging T2 lesions at week 24, 48 and 96 is calculated as the sum of the individual number of new and/or enlarging lesions at each visit. Data from other unscheduled assessments is included in this summary or analysis.	Weeks 24, 48, 96
Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan	Mean number of new and/or enlarging T2 hyperintense lesions per MRI scan: Total number of new and/or enlarging T2 hyperintense lesions divided by the total number of interpretable MRI scans	Weeks 24, 48, 96
Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume		Weeks 48, 96
Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume		Weeks 48, 96
Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume		Weeks 48, 96
Adjusted Mean Percentage Change From Baseline in Brain Volume		Weeks 24, 48, 96
Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume		Weeks 48, 96
Adjusted Mean Percentage Change From Baseline in White Matter Volume		Weeks 48, 96
Mean Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span. The higher the results, the better processing speed/working memory.	Baseline, Weeks: 48, 96
Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.	Baseline, Weeks 48, 96
Percentage Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span.	Baseline, Weeks 48, 96
Percentage Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score	Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.	Baseline, Weeks: 48, 96
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Baseline up to to 96 weeks after the end of the Treatment Period

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Vermersch P, Oreja-Guevara C, Siva A, Van Wijmeersch B, Wiendl H, Wuerfel J, Buffels R, Kadner K, Kuenzel T, Comi G; CASTING Investigators. Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis with suboptimal response to prior disease-modifying therapies: A primary analysis from the phase 3b CASTING single-arm, open-label trial. Eur J Neurol. 2022 Mar;29(3):790-801. doi: 10.1111/ene.15171. Epub 2021 Nov 25.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2016
• Primary Completion (Actual): October 25, 2019
• Study Completion (Actual): December 15, 2020

Study Registration Dates

• First Submitted: August 5, 2016
• First Submitted That Met QC Criteria: August 5, 2016
• First Posted (Estimate): August 10, 2016

Study Record Updates

• Last Update Posted (Actual): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 25, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: MA30005; 2015-005597-38 (EudraCT Number)