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)

NCT ID: NCT02861014

Last Updated: 2022-01-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 681 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-09
• Study Completion Date: 2020-12-15

Brief Summary

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.

Conditions

Multiple Sclerosis, Relapsing-Remitting

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ocrelizumab

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Other Intervention Names

RO4964913

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

St George Hospital

Kogarah, New South Wales, New South Wales, Australia

Hospital Erasme

Brussels, , Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

UZ Antwerpen

Edegem, , Belgium

UZ Gent

Ghent, , Belgium

CHU Tivoli

La Louvière, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Nationaal MS Centrum

Melsbroek, , Belgium

Revalidatie en MS Centrum

Overpelt, , Belgium

Fakultni nemocnice u sv. Anny; Neurologicka klinika

Brno, , Czechia

Nemocnice Jihlava; NEU-Neurologicke oddeleni

Jihlava, , Czechia

VFN Praha Poliklinika Rs Centrum - Budova A

Prague, , Czechia

Fakultni nemocnice Motol; Neurologicka klinika

Prague, , Czechia

Aarhus Universitetshospital, Neurologisk Afd. F, Skleroseklinikken

Aarhus N, , Denmark

Rigshospitalet Glostrup; Neurologisk Klinik

Glostrup Municipality, , Denmark

Odense Universitetshospital, Neurologisk Afdeling N

Odense C, , Denmark

Sydjysk Skleroseklinik - Sønderborg

Sønderborg, , Denmark

East Tallinn Central Hospital; Neurology Department

Tallinn, , Estonia

West Tallinn Central Hospital

Tallinn, , Estonia

Tartu University Hospital

Tartu, , Estonia

Terveystalo Tampere

Tampere, , Finland

Mehiläinen Neo Turku

Turku, , Finland

CHU de Besancon Hopital Jean Minjoz; Service de Neurologie

Besançon, , France

Groupe Hospitalier Pellegrin; Service de neurochirurgie B

Bordeaux, , France

Hopital Neurologique et Neurochirurgical Pierre Wertheimer; Service de Neurologie A

Bron, , France

Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B

Clermont-Ferrand, , France

Hopital Roger Salengro; Service de Neurologie

Lille, , France

CHU de la Timone - Hopital d Adultes; Service de Neurologie

Marseille, , France

Hopital Gui de Chauliac; Neurologie

Montpellier, , France

Hôpital Guillaume et René Laënnec; Service Neurologie

Nantes, , France

Hôpital Pasteur; Service de Neurologie

Nice, , France

Fondation Rothschild; Service de Neurologie

Paris, , France

Groupe Hospitalier Pitié- Salpétrière; Service Neurologie

Paris, , France

Hôpital Maison Blanche; Service de Neurologie

Reims, , France

Hôpitaux Universitaires de strasbourg - hôpital civil

Strasbourg, , France

CHU toulouse - Hôpital Purpan; Departement de Neurologie

Toulouse, , France

CHRU - Hôpital Bretonneau; Neurologie

Tours, , France

Klinikum Augsburg, Neurologische Klinik und klinische Neurophysiologie

Augsburg, , Germany

Marianne-Strauß-Klinik; Behandlung Kempfen für Multip Sklero Kranke gemeinnütz GmbH

Berg, , Germany

Charite - Universitatsmedizin Berlin; Klinik fur Neurologie

Berlin, , Germany

Praxis Dr. Said Masri

Berlin, , Germany

Gemeinschaftspraxis Dr.med. Reinhard Ehret/Dr. med Wolfram von Pannwitz

Berlin, , Germany

Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie

Berlin, , Germany

St. Josef-Hospital, Klinik für Neurologie

Bochum, , Germany

Gesundheitszentrum St. Johannes Hospital; Neurolog. Gemeinschaftspraxis Dres. Schmidt, Neudecker etc

Bonn, , Germany

Studienzentrum für Neurologie und Psychiatrie

Böblingen, , Germany

PNP Buchholz, Praxis für Neurologie - Psychiatrie, Dres. Dee/Gößling/Hoge

Buchholz, , Germany

Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

Dresden, , Germany

Gemeinschaftspraxis für Neurologie; Dr. Katrin Schulte, Dr. Nils Richter, Dr. Margarete Capito

Düsseldorf, , Germany

NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich

Erbach/Odenwald, , Germany

Universitaetsklinikum Frankfurt; Klinik für Neurologie

Frankfurt, , Germany

Universitätsklinikum Freiburg, Klinik für Neurologie und Neurophysiologie

Freiburg im Breisgau, , Germany

Universiätsklinikum Hamburg-Eppendorf , Multiple Sklerose Tagesklinik u. Ambulanz Neurol. Poliklinik

Hamburg, , Germany

Neurologische Praxisgemeinschaft Hamburger-Straße; Dres. Müller-Habich/Emrich/Vogt

Hamburg, , Germany

MultipEL Studies - Institut für klinische Studien

Hamburg, , Germany

Henriettenstiftung Hannover; Klinik fuer Neurologie und Klinische Neurophysiologie

Hanover, , Germany

Neurologische Klinik, Universitätsklinikum Heidelberg

Heidelberg, , Germany

Oberhavel Kliniken GmbH, Klinik Hennigsdorf, Neurologie

Hennigsdorf, , Germany

Neurozentrum am Klosterforst in Itzehoe

Itzehoe, , Germany

Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische

Kassel, , Germany

PANAKEIA - Arzneimittelforschung Leipzig GmbH

Leipzig, , Germany

Universitätsklinikum Magdeburg,Otto-von-Guericke-Universität A.ö.R., Klinik für Neurologie

Magdeburg, , Germany

Universitaetsklinikum Mainz - PS; Klinik und Poliklinik fuer Neurologie

Mainz, , Germany

Universitaetsklinikum Marburg; Klinik fuer Neurologie

Marburg, , Germany

Max-Planck-Institut für Psychiatrie

München, , Germany

Klinikum Grosshadern der LMU; Neuroimmunologie II

München, , 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

Ruppiner Kliniken, Hochschulklinikum der Medizinischen Hochschule Brandenburg, Klinik für Neurologie

Neuruppin, , Germany

AMEOS Klinikum Oldenburg, Klinik für Neurologie und Neurophysiologie

Oldenburg in Holstein, , Germany

St. Josefs-Krankenhaus, Klinik für Neurologie

Potsdam, , Germany

NeuroConcept AG C/O mind mvz GmbH

Stuttgart, , Germany

Universitätsklinikum Tübingen, Zentrum für Neurologie

Tübingen, , Germany

NeuroPoint, Gesellschaft für vorbeugende Gesundheitspflege mbH

Ulm, , Germany

Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz

Westerstede, , Germany

Cork University Hospital; Clinical Research Facility

Cork, , Ireland

Beaumont Hospital

Dublin, , Ireland

St Vincents University Hospital

Dublin, , Ireland

Ospedale SS. Annunziata - Clinica Neurologica - Centro Sclerosi Multipla

Chieti, Abruzzo, Italy

Ospedale San Salvatore; Clinica Neurologica - Centro Sclerosi Multipla

L’Aquila, Abruzzo, Italy

Ospedale Dimiccoli Barletta; Dipartimento Testa-Collo - UO Neurologia

Barletta, Apulia, Italy

IRCCS Ospedale Casa Sollievo Della Sofferenza; SC Neurologia

San Giovanni Rotondo, Apulia, 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

Ospedale Bellaria; Istituto delle Scienze Neurologiche - UO RIABILITAZIONE SCLEROSI MULTIPLA

Bologna, Emilia-Romagna, Italy

Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla

Rome, Lazio, Italy

Ospedale S.Camillo Forlanini; UOSD Day Hospital Neurologico e Neurochirurgico

Rome, Lazio, Italy

Policlinico Universitario A. Gemelli; UOC Neurologia - Centro Sclerosi Multipla

Rome, Lazio, Italy

Azienda Ospedaliera Sant'Andrea; UOC Neurologia

Rome, Lazio, Italy

Irccs A.O.U.San Martino Ist; Dinogmi

Genoa, Liguria, Italy

ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla

Bergamo, Lombardy, Italy

Ospedale S.Antonio Abate; Neurologia 2 - Sclerosi Multipla e Recupero Neurologico

Gallarate, Lombardy, Italy

Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico; UOSD Malattie Neurodegenerative

Milan, Lombardy, Italy

IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla

Milan, Lombardy, Italy

Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari

Milan, Lombardy, Italy

Ospedale Civile di Montichiari; Centro Sclerosi Multipla

Montichiari, Lombardy, Italy

IRCCS Istituto Neurologico C. Mondino-Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla

Pavia, Lombardy, Italy

IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla

Pozzilli, Molise, Italy

Ospedale Binaghi; Centro Sclerosi Multipla

Cagliari, Sardinia, Italy

AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla

Catania, Sicily, Italy

Fondazione Istituto S. Raffaele - Giglio; UO Neurologia

Cefalù, Sicily, Italy

AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla

Palermo, Sicily, Italy

AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia

Palermo, Sicily, Italy

AOU Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi; SOD Clinica Neurologica-Am.Sclerosi Multipla

Ancona, The Marches, Italy

AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)

Florence, Tuscany, Italy

AOUC Azienda Ospedaliero-Universitaria Careggi; Neurologia 2

Florence, Tuscany, Italy

AOU Senese - Presidio Ospedaliero Le Scotte; UOSA Neurologia Sperimentale

Siena, Tuscany, Italy

AO di Perugia - Ospedale S. Maria della Misericordia; Clinica Neurologica

Perugia, Umbria, Italy

Azienda Ospedaliera di Padova; Clinica Neurologica

Padua, Veneto, Italy

Policlinico G.B. Rossi; Dip. Scienze Neurologiche Biomediche - Neurologia B - Amb. Sclerosi Multipla

Verona, Veneto, Italy

Amphia Ziekenhuis

Breda, , Netherlands

St. Antonius Ziekenhuis Nieuwegein

Nieuwegein, , Netherlands

Maasstadziekenhuis

Rotterdam, , Netherlands

Zuyderland Medisch Centrum - Sittard Geleen

Sittard-Geleen, , Netherlands

Sint Elizabeth Ziekenhuis

Tilburg, , Netherlands

Haukeland Universitetssykehus

Bergen, , Norway

Sykehuset Buskerud HF; Nevrologisk avdeling

Drammen, , Norway

Hospital Universitari de Bellvitge; Servicio de Neurologia

L'Hospitalet de Llobregat, Barcelona, Spain

Hospital General de Castellon; Servicio de Neurología

Castellon, Castellon, Spain

Hospital Universitari de Girona Dr. Josep Trueta; Servicio de Neurologia

Salt, Girona, Spain

Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia

A Coruña, LA Coruña, Spain

Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Neurología

Lleida, Lerida, Spain

Hospital Quiron de Madrid; Servicio de Neurologia

Pozuelo de Alarcón, Madrid, Spain

Complejo Hospitalario Universitario de Vigo - Xeral Cies; Servicio de Neurologia

Vigo, Pontevedra, Spain

Hospital Universitario Central de Asturias; Servicio de Neurología

Oviedo, Principality of Asturias, Spain

Hospital del Mar; Servicio de Neurologia

Barcelona, , Spain

Hospital Vall d'Hebron; Servicio de Neurología

Barcelona, , Spain

Hospital Puerta del Mar; Sevicio de Neurologia

Cadiz, , Spain

Universitario de La Princesa; Servicio de Neurología

Madrid, , Spain

Hospital Universitario Clínico San Carlos; Servicio de Neurología

Madrid, , Spain

Hospital Universitario 12 de Octubre; Servicio de Neurologia

Madrid, , Spain

Hospital Universitario La Paz; Servicio de Neurologia

Madrid, , Spain

Hospital Universitario Virgen de Arrixaca; Servicio de Neurología

Murcia, , Spain

Hospital Universitario Virgen Macarena; Servicio de Neurologia

Seville, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Neurologia

Valencia, , Spain

Hospital Universitario la Fe; Servicio de Neurologia

Valencia, , Spain

Sahlgrenska Sjukhuset; Neurology

Gothenburg, , Sweden

Länssjukhuset Ryhov; Medicinkliniken / Neurologmottagningen

Jönköping, , Sweden

Centrum för Neurologi

Stockholm, , Sweden

Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik

Basel, , Switzerland

CHUV Lausanne Méd.Neurologie

Lausanne, , Switzerland

Hacettepe University Medical Faculty; Neurology

Ankara, , Turkey (Türkiye)

Istanbul Uni Istanbul Medical Faculty

Istanbul, , Turkey (Türkiye)

Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali

Istanbul, , Turkey (Türkiye)

Ege University Medical Faculty

Izmir, , Turkey (Türkiye)

Kocaeli University Hospital; Department of Neurology

Kocaeli, , Turkey (Türkiye)

Mersin University Medical Faculty; Neurology

Mersin, , Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac.; Neurology

Samsun, , Turkey (Türkiye)

Karadeniz Tecnical Uni. Med. Fac.; Neurology

Trabzon, , Turkey (Türkiye)

New Queen Elizabeth Hospital Birmingham

Birmingham, , United Kingdom

Western General Hospital

Edinburgh, , United Kingdom

Royal Devon and Exeter Hospital (Wonford)

Exeter, , United Kingdom

Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Raigmore Hospital

Inverness, , United Kingdom

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

The Royal London Hospital

London, , United Kingdom

Kings College Hospital

London, , United Kingdom

Charing Cross Hospital

London, , United Kingdom

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Salford Royal NHS Foundation Trust

Salford, , United Kingdom

Royal Hallamshire Hospita

Sheffield, , United Kingdom

Morriston Hospital

Swansea, , United Kingdom

Royal Cornwall Hospital

Truro, , United Kingdom

Countries

Australia; Belgium; Czechia; Denmark; Estonia; Finland; France; Germany; Ireland; Italy; Netherlands; Norway; Spain; Sweden; Switzerland; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34748672 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-005597-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MA30005

Identifier Type: -

Identifier Source: org_study_id