Multiple Sclerosis, Relapsing-RemittingPhase 3NCT03085810
Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)
A Phase 3 study testing Ocrelizumab in people with Multiple Sclerosis, Relapsing-Remitting, run by Hoffmann-La Roche at 193 sites in 29 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Ocrelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,225 participants
- Where
- 193 sitesin 29 countries
- Study dates
- 24 Mar 2017to 27 Apr 2023
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
- Any previous serious IRRs experienced with ocrelizumab treatment
Trial locations and contacts
193 sites in 29 countries.
193 sites in 29 countries
United States26 sites
Shepherd Center Inc.
Atlanta, Georgia, 30309
University of Colorado Denver
Aurora, Colorado, 80045
University of Maryland Medical Center; Department of Neurology
Baltimore, Maryland, 21201
The NeuroMedical Center
Baton Rouge, Louisiana, 70810
Kane Hall Barry Neurology
Bedford, Texas, 76021
Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40
Cleveland, Ohio, 44195
Neurology Specialists, Inc
Dayton, Ohio, 45417
Advanced Neurology of Colorado, LLC
Fort Collins, Colorado, 80528
Neurology Center of New England
Foxborough, Massachusetts, 02035
Minneapolis Clinic of Neurology
Golden Valley, Minnesota, 55422
Neurology Associates PA
Hickory, North Carolina, 28602
University of California Irvine
Irvine, California, 92697
Cleveland Clinic Lou Ruvo; Center for Brain Research
Las Vegas, Nevada, 89106
Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders
Milwaukee, Wisconsin, 53215
Vanderbilt University Medical Center
Nashville, Tennessee, 37212
Columbia University Medical Center
New York, New York, 10032
College Park Family Care Ctr
Overland Park, Kansas, 66212
Island Neurological Associates, P.C.
Plainview, New York, 11803
Maine Medical Center
Scarborough, Maine, 04074
KI Health Partners, LLC; New England Institute for Clinical Research
Stamford, Connecticut, 06905
Palo Alto Medical Foundation Research Center
Sunnyvale, California, 94086
MultiCare Health System Institute for Research and Innovation
Tacoma, Washington, 98405
University of South Florida - Bradenton
Tampa, Florida, 33612
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Dragonfly Research, LLC
Wellesley, Massachusetts, 02481
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
France20 sites
CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
Besançon, 25030
Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
Bordeaux, 33076
Hopital Pierre Wertheimer; Neurologie D
Bron, 69677
CHU de Caen Hopital Cote de Nacre
Caen, 14033
CHU Hopital Gabriel Montpied; Service de Neurologie
Clermont-Ferrand, 63003
CH de Gonesse; Neurologie
Gonesse, 95503
CHU de Grenoble; Neurologie
La Tronche, 38700
Hopital Gui de Chauliac; Neurologie
Montpellier, 34295
Hopital Central - CHU de Nancy; Service de Neurologie
Nancy, 54035
Hôpital Guillaume et René Laënnec; Service Neurologie
Nantes, 44805
Hôpital Pasteur; Service de Neurologie
Nice, 06002
CHU de Nîmes Hopital Caremeau; Service de Neurologie
Nîmes, 30900
Hôpital de Poissy; Service neurologie
Poissy, 78300
Centre Hospitalier Universitaire de Rennes
Rennes, 35033
CHU de Rouen Hopital; Service de Neurologie
Rouen, 76031
CHU de Strasbourg
Strasbourg, 67098
Hopital Foch; Neurologie
Suresnes, 92151
HIA de Toulon hôpital militaire; Neurologie
Toulon, 83041
CHU toulouse - Hôpital Purpan; Departement de Neurologie
Toulouse, 31059
CHRU - Hôpital Bretonneau; Neurologie
Tours, 37000
Germany18 sites
Praxis Dr.med. Sylvia Menck, Fachärztin für Neurologie und Psychiatrie
Barsinghausen, 30890
Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
Berlin, 13347
Studienzentrum Dr. Bischof GmbH
Böblingen, 71034
St. Josef-Hospital, Klinik für Neurologie
Bochum, 44791
Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
Dresden, 01307
Universitätsklinikum Düsseldorf; Klinik für Neurologie
Düsseldorf, 40225
NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich
Erbach/Odenwald, 64711
Universitätsklinikum Essen (AöR); Klinik für Neurologie
Essen, 45147
MultipEL Studies - Institut für klinische Studien
Hamburg, 22179
Universitaetsklinikum Heidelberg
Heidelberg, 69120
Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische
Kassel, 34121
Uniklinik Schleswig-Holstein; Neuroimmunologie, Institut für Klinische Chemie + Klinik f. Neurologie
Kiel, 24105
Universitaetsklinikum Marburg; Klinik fuer Neurologie
Marburg, 35043
Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
München, 81675
Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie
Münster, 48149
Praxis Dr. med. Bergmann
Neuburg am Inn, 86633
Asklepios Kliniken Schildautal Seesen; Klinik für Neurologie
Seesen, 38723
Universitätsklinikum Tübingen, Zentrum für Neurologie
Tübingen, 72076
Italy16 sites
AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla
Catania, Sicily, 95123
A.O.U. Mater Domin; U.O. NEUROLOGIA
Catanzaro, Calabria, 88100
AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)
Florence, Tuscany, 50134
Irccs A.O.U.San Martino Ist; Dinogmi
Genoa, Liguria, 16132
Ospedale Misericordia USL9 di Grosseto; U.O. Neurologia
Grosseto, Tuscany, 58100
IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
Milan, Lombardy, 20132
Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari
Milan, Lombardy, 20133
Ospedale Civile di Montichiari; Centro Sclerosi Multipla
Montichiari, Lombardy, 25018
A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
Naples, Campania, 80131
Università degli Studi della Campania Luigi Vanvitelli; Dip. Ass. Integrato Med Int-II Clinica Neur
Naples, Campania, 80131
AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia
Palermo, Sicily, 90146
IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla
Pozzilli, Molise, 86077
Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
Rome, Lazio, 00133
Azienda Ospedaliera Sant'Andrea; UOC Neurologia
Rome, Lazio, 00189
Ospedale Le Scotte; Clinica Neurologica e Malattie Neurometaboliche
Siena, Tuscany, 53100
Ospedale Cattinara; Amb Studio Sclerosi Multipla, Clinica Neurlogica
Trieste, Friuli Venezia Giulia, 34149
United Kingdom10 sites
Cambridge University Hospitals NHS Foundation Trust
Cambridge, CB2 0QQ
Queen Elizabeth University Hospital
Glasgow, G51 4TF
Royal Free Hospital
London, NW3 2QS
King'S College Hospital
London, SE5 9RS
Charing Cross Hospital
London, W6 8RF
National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases
London, WC1N 3BG
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP
Derriford Hospital
Plymouth, PL6 8BT
Salford Royal NHS Foundation Trust
Salford, M6 8HD
Abertawe and Bro Morgannwg NHS Trust; Clinical Researdh Institute
Swansea, SA6 6NL
Australia9 sites
Box Hill Hospital; Department of Neurology
Box Hill, Victoria, 3128
Brain and Mind Centre
Camperdown, New South Wales, 2050
Austin Hospital; Department of Neurology
Heidelberg, Victoria, 3084
Liverpool Hospital
Liverpool, New South Wales, 2170
Perron Institute for Neurological and Translational Science
Nedlands, Western Australia, 6009
John Hunter Hospital
New Lambton, New South Wales, 2305
Royal Melbourne Hospital; Department of Neurology
Parkville, Victoria, 3050
Royal North Shore Hospital; Department of Neurology
St Leonards, New South Wales, 2065
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Turkey (Türkiye)9 sites
Hacettepe University Medical Faculty; Neurology
Ankara, 06100
Gazi University Medical Faculty; Departmant of Norology
Ankara, 06500
Mustafa Kemal Ataturk UTF; Department of norology
Hatay, 31001
Istanbul University Istanbul Medical Faculty; Neurology
Istanbul, 34093
Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
Istanbul, 34098
Istanbul Bilim Universty Medical Fac.
Istanbul, 34394
Selcuk University Medical Faculty; Norology department
Istanbul, 42131
Ondokuz Mayis Univ. Med. Fac.; Neurology
Samsun, 55139
Karadeniz Tecnical Uni. Med. Fac.; Neurology
Trabzon, 61080
Poland8 sites
Neurocentrum Bydgoszcz sp. z o.o
Bydgoszcz, 85-796
COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny
Gdansk, 80-803
Care Clinic
Katowice, 40-568
Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.
Krakow, 31-637
Centrum Neurologii Krzysztof Selmaj
Lodz, 90-324
Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
Lublin, 20-410
Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
Warsaw, 02-097
Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
Warsaw, 02-957
Belgium7 sites
AZ Sint Jan
Bruges, 8000
UZ Brussel
Brussels, 1090
Cliniques Universitaires St-Luc
Brussels, 1200
UZ Antwerpen
Edegem, 2650
CHU Tivoli
La Louvière, 7100
CHU Sart-Tilman
Liège, 4000
Revalidatie en MS Centrum
Overpelt, 3900
Canada7 sites
Clinique NeuroOutaouais
Gatineau, Quebec, J8Y 1W2
Recherche Sepmus Inc.
Greenfield Park, Quebec, J4V 2J2
London Health Sciences Centre Uni Campus
London, Ontario, N6A 5A5
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4
Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9
Sunnybrook Health Science Centre
Toronto, Ontario, M4N 3M5
UBC Hospital; Div of Neurology, Dept of Medicine
Vancouver, British Columbia, V6T 1Z3
Spain7 sites
Hospital General Universitario de Alicante; Servicio de Neurología
Alicante, 03010
Hospital de Cruces; Servicio de Neurologia
Barakaldo, Vizcaya, 48903
Hospital del Mar; Servicio de Neurologia
Barcelona, 08003
Hospital Vall d'Hebron; Servicio de Neurología
Barcelona, 08035
Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
Madrid, 28222
Hospital General Universitario Morales Meseguer; Servicio de Neurología
Murcia, 30008
Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia
Santa Cruz de Tenerife, Tenerife, 38010
Hungary5 sites
Semmelweis Egyetem AOK; Neurologiai Klinika
Budapest, 1083
Budapesti Uzsoki Utcai Kórház
Budapest, 1145
Jahn Ferenc Dél-Pesti Kórház
Budapest, 1204
VALEOMED Diagnosztikai Központ
Esztergom, 2500
Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika
Szeged, 6725
Portugal5 sites
Hospital Garcia de Orta; Servico de Neurologia
Almada, 2801-951
Hospital de Braga; Servico de Neurologia
Braga, 4710-243
HUC; Servico de Neurologia
Coimbra, 3000-075
Hospital Beatriz Angelo; Servico de Neurologia
Loures, 2674-514
Hospital Geral de Santo Antonio; Servico de Neurologia
Porto, 4099-001
Switzerland5 sites
Universitätsspital Basel; Neurologie
Basel, 4031
Inselspital Bern Medizin Neurologie; Neurologische Poliklinik
Bern, 3010
Luzerner Kantonsspital Luzern Medizin Neurologie
Lucerne, 6004
Ospedale Regionale di Lugano - Civico; Neurologia
Lugano, 6903
Kantonsspital; Neurologische Klinik
Sankt Gallen, 9007
Austria4 sites
Medizinische Universität Graz; Universitätsklinik für Neurologie
Graz, 8036
Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
Innsbruck, 6020
Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie
Salzburg, 5020
Medizinische Universität Wien; Univ.Klinik fuer Neurologie
Vienna, 1090
Brazil4 sites
Hospital das Clinicas - UFMG
Belo Horizonte, Minas Gerais, 31270-901
Instituto de Neurologia de Curitiba
Curitiba, Paraná, 81210-310
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Hospital das Clinicas - FMUSP
São Paulo, São Paulo, 05403-010
Netherlands4 sites
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, 5223 GZ
VU Medisch Centrum; Afdeling Neurologie
Amsterdam, 1081 HV
Groene Hart Ziekenhuis
Gouda, 2803 HH
Zuyderland Medisch Centrum - Sittard Geleen
Sittard-Geleen, 6162 BG
Slovakia4 sites
Univerzitna nemocnica Bratislava, Nemocnica Staré Mesto; I. Neurologická klinika SZU a UNB
Bratislava, 813 69
Univerzitna nemocnica Bratislava - Nemocnica Ruzinov; Neurologicka klinika SZU a UNB
Bratislava, 826 06
GB NeuroPRAKTIK, s.r.o
Nitra, 949 11
Fakultna nemocnica Trnava
Trnava, 917 75
Argentina3 sites
Centro de Especialidades Neurológicas y Rehabilitación - CENyR
Buenos Aires, C1424
Hospital Churruca Visca
Buenos Aires, C1437JCP
Fundacion Rosarina de Neurorehabilitacion
Rosario, S2000BZL
Bulgaria3 sites
Shat Np Sveti Naum; 3Rd Clinic of Neurology
Sofia, 1113
Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.
Sofia, 1309
UMHAT Alexandrovska, EAD; Neurology
Sofia, 1431
Denmark3 sites
Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.
Aalborg, 9000
Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken
Aarhus N, 8200
Rigshospitalet; Neurologisk Klinik Glostrup
Glostrup Municipality, 2600
Mexico3 sites
Neurociencias Estudios Clinicos S.C.
Culiacán, Sinaloa, 80020
Hospital General de Mexico
Mexico, Tlaxcala, 06726
Unidad de investigacion en salud (UIS); Neurociencias
Mexico City, 14050
Romania3 sites
Spitalul Universitar de Urgenta Bucuresti
Bucharest, 11172
Spitalul Clinic Judetean Sibiu
Sibiu, 550245
Spitalul Clinic Judetean de Urgenta Mures
Târgu Mureş, 540136
Sweden3 sites
Sahlgrenska Sjukhuset; Neurology
Gothenburg, 413 45
Centralsjukhuset; Neurologi och rehabiliteringskliniken
Karlstad, 651 85
Centrum för Neurologi
Stockholm, 113 41
Norway2 sites
Akershus universitetssykehus HF; Nevroklinikken S203
Lørenskog, 1478
Stavanger Universitetssykehus, Helse Stavanger HF
Stavanger, 4011
Slovenia2 sites
University Medical Centre; Neurology
Ljubljana, 1000
University Medical Centre Maribor
Maribor, 2000
Lebanon1 site
American University of Beirut - Medical Center
Beirut, 1107 2020
About this study
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
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.
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Ocrelizumab
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OcrelizumabDrug
Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Ocrelizumab | Experimental | 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. Receives: Drug: Ocrelizumab |
| Substudy Group 1 | Active comparator | 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 Receives: Drug: Ocrelizumab |
| Substudy Group 2 | Experimental | 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 Receives: Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS)
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits for a minimum of 24 weeks/48 weeks.
Measured: Baseline up to 4 years
Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS
CDI is defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Measured: At Weeks 24 and 48 during Year 1
Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Measured: Year 1 (Weeks 24 and 48)
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS
CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Measured: At Weeks 48, 72 and 96 during Year 2
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Measured: Year 2 (Weeks 72 and 96)
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS
CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Measured: At Weeks 144, 168 and 192 during Year 4
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Measured: Year 4 (Weeks 168 and 192)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS
Measured: Year 1 (Week 48)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS
Measured: Year 2 (Week 96)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS
Measured: Year 3
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS
Measured: Year 4
Mean Change From Baseline in EDSS Score at Week 24
Measured: From Baseline to Week 24
Mean Change From Baseline in EDSS Score at Week 48
Measured: From Baseline to Week 48
Mean Change From Baseline in EDSS Score at Week 72
Measured: From Baseline to Week 72
Mean Change From Baseline in EDSS Score at Week 96
Measured: Baseline, Week 96
Mean Change From Baseline in EDSS Score at Week 120
Measured: Baseline, Week 120
Mean Change From Baseline in EDSS Score at Week 144
Measured: Baseline, Week 144
Mean Change From Baseline in EDSS Score at Week 168
Measured: Baseline, Week 168
Mean Change From Baseline in EDSS Score at Week 192
Measured: Baseline, Week 192
Percentage of Participants Without 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.
Measured: Baseline up to 4 years
Percentage of Participants Without Relapse
Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
Measured: Baseline up to 4 years
Annualized Relapse Rate
Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. The adjusted annualized relapse rate is reported which is:
Adjusted by age at disease diagnosis, Baseline EDSS, Presence of T1 Gd-enhanced lesion at screening and Presence of relapses in the last year prior to enrollment. Log-transformed exposure time is included as an offset variable.
The report contains data up to week 192 of the treatment period of each individual participant.
Measured: Baseline up to 4 years
Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy
Measured: Week 24 through Week 144
Secondary outcomes (25)
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.
Measured: Week 192
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. Event-free rate
Measured: Weeks 96, 144, 192
Percentage of Participants Without Protocol-defined Event of 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.
Measured: Weeks 96, 192
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.
Measured: Weeks 96, 192
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total
MSFC combines the following: Timed 25 Foot Walk Test [T25FWT] for leg function \&ambulation measured in seconds (sec). The longer it takes to walk, higher the score indicating deterioration; 9 Hole Peg Test [9HPT] for arm \& handf unction measured in sec. Higher score=more time taken to complete test indicating deterioration. Paced Auditory Serial Addition Test [PASAT] for cognitive function (score range: 0-60, higher score=better cognitive processing speed). MSFC composite={[Average(1/9-HPT)-Baseline Mean(1/9-HPT)/Baseline Std Dev(1/9-HPT)]+[-(Average T25FWT-Baseline Mean T25FWT)/Baseline Std-Dev T25FWT]+[(PASAT-3-BaselineMean PASAT-3)/Baseline Std Dev PASAT-3]}/ 3.0. MSFC is based on the concept that scores for these 3 dimensions are combined to create a single score to detect change over time in a group of MS patients. Higher composite score=better overall function. Lower score=worse overall function. Higher mean change in total MSFC score=functional improvement at cohort level.
Measured: Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score.
The change in the mean score of T25FW is reported below. The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, the higher score, which indicates deterioration. Lower times indicate better performance and greater mobility. Higher times indicate worse performance and greater impairment. Subsequently, the lower the mean change in the score over time, the better performance.
Measured: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score
The mean change in 9 Hole Peg Test (9HPT)-score is reported. Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. The number of seconds it takes to complete the test, the higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.
Measured: Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score
Mean change in the Paced Auditory Serial Addition Test [PASAT] score is reported. PASAT measures cognitive function. A total of 60 single digit numbers are presented by an audiotape/CD-rom at a constant rate in every 3 seconds (PASAT-3). Participants are required to add each new number to the one immediately before it. Due to the relative complexity of this test, a practice trial with a set of 10 numbers should be performed before the original test. Participants are allowed up to 3 practice trials. Two sets of numbers (forms A \& B) are developed to be used alternatively in every visit to minimize memorizing. The number of correct answers is recorded. The PASAT score ranges from 0 to 60, with higher values representing a better outcome in cognitive processing speed. Subsequently, higher values in mean changes from baseline over the study time indicate improvement in cognitive function.
Measured: Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT)
BICAMS is assessing cognitive processing speed and verbal and visual memory. SDMT assesses 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 second time span. The higher the results, the better processing speed/working memory.
Measured: Baseline, Weeks 48, 96, 144, 192
Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II)
BICAMS assesses cognitive processing speed and verbal and visual memory. The CLVT-II is an assessment of verbal learning and memory which measures recall and recognition scores, encoding strategies, learning rates and error types. A list learning task with 16 words from 4 semantic categories are read over a series of 5 list presentations. Recall is assessed after learning and at a 20-minute delay. The maximum possible score is 80 and a minimum is 0. A higher score indicated better recall.
Measured: Baseline, Weeks 48, 96, 144, 192
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R)
BICAMS assesses cognitive processing speed and verbal and visual memory. BVMT-R assesses 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.
Measured: Baseline, Weeks 48, 96, 144, 192
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI
Number of Lesions are categorized as followed: 1, 2, 3, >1, >3
Measured: Weeks 24, 48, 96, 144, 192
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI
Number of Lesions are categorized as followed: 1, 2, 3, >1
Measured: Baseline, Weeks 24, 48, 96, 144, 192
Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI
Measured: Baseline, Weeks 48, 96, 144, 192
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI
Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI was measured for its volumes.
Measured: Baseline, Weeks 8, 24, 48, 96, 144, 192
Change From Baseline in Brain Volume as Detected by Brain MRI
Percentage change from Normalized brain volume in cm3 (cubic centimeter)values are reported
Measured: From Baseline to Weeks 24, 48, 96, 144, 192
Percentage of Participants Without Treatment Discontinuation
Measured: Baseline up to 4 years
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score
WPAI scale measures impact of health problems on work productivity and regular activities: Absenteeism (Work Time Missed) measuring % of work time missed due to health issues; Presenteeism:Calculated as the percentage of impairment while working due to health problems. Overall Work Impairment:Calculated by combining absenteeism and presenteeism using the formula:Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism This formula accounts for both the time missed and the reduced productivity while at work.
Activity Impairment: Calculated as the percentage of impairment in regular activities outside of work. Range: Each component is scored as 0%-100%). Higher % indicate greater impairment and worse outcomes.
Measured: Baseline, Weeks 24, 48, 96, 120, 144, 192
SymptoMScreen Composite Score
The SMSS consists of 12 items which are assessed on a seven-point Likert scale that ranges from 0 (not at all affected) to 6 (total limitation) [7]. The total score ranges from 0 to 72, with higher scores indicating more severe symptom endorsement.
Measured: Baseline, Weeks 24, 48, 96, 144, 192
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score
The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a questionnaire to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective, which includes 29 items self-reported measures associated with a physical scale and 9 items with a psychological scale. MSIS-29 scales are generated by summing items and it's ranging from 29-145'. The higher total MSIS-29 scores indicate a greater degree of disability. The mean change in MSIS-29 scores from baseline is reported. The decreasing values in the mean change from baseline indicate functional improvement from patients' perspective
Measured: Baseline, Weeks 24, 48, 96, 144, 192
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Baseline up to 4 years
Substudy: Number of Participants With IRR Overall and by Dose at Randomization
Measured: From Week 24 to Week 144
Substudy: Severity of IRRs
The number of participants with IRRs by most extreme intensity were reported (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 =life-threatening, grade 5 = fatal). Multiple IRRs in one participant are counted only once at the most extreme (highest) intensity observed.
Measured: From Week 24 to Week 144
Substudy: Number of IRR Symptoms
Measured: From Week 24 to Week 144
Substudy: IRRs Leading to Treatment Discontinuation
Measured: From Week 24 to Week 144
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2017
- Study start24 Mar 2017
- Primary completion27 Apr 2023
- Study completion27 Apr 2023
Why it stopped: The study was terminated earlier as the study sponsor collected sufficient data to perform all analyses as per pre-specified endpoints in the study protocol.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1,225 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03085810
- Sponsor's protocol ID
- MA30143
- Other IDs
- 2016-002937-31, 2016
- Status last verified
- Dec 2024
- First submitted
- 16 Mar 2017
- Last updated
- 15 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
Publications
Vermersch P, Benedict RHB, Van Wijmeersch B, Cutter G, Kister L, Oreja-Guevara C, Siva A, Wiendl H, Wuerfel J, El Azzouzi B, Kuenzel T, Buffels R, Craveiro L, Dirks P, Comi G. Efficacy and Safety of Patients With Relapsing Multiple Sclerosis Switching to Ocrelizumab Due to Suboptimal Treatment Response: Results of the 4-Year CASTING-LIBERTO Trial. Eur J Neurol. 2026 Jun;33(6):e70628. doi: 10.1111/ene.70628.
PubMed 42328798Garcia A, Rodriguez S, Dugast E, Lebrun-Frenay C, Thouvenot E, de Seze J, Le Page E, Vukusic S, Doghri I, Berger E, Casez O, Labauge P, Ruet A, Raposo C, Le Frere F, Nicot AB, Wiertlewski S, Gourraud PA, Michel L, Berthelot L, Laplaud DA. Durable B-Cell Impairment While Sparing IgA B Cells After Ocrelizumab Therapy in Multiple Sclerosis. Ann Clin Transl Neurol. 2025 Nov;12(11):2271-2285. doi: 10.1002/acn3.70135. Epub 2025 Aug 8.
PubMed 40781066Kappos L, Yiu S, Reucassel J, Oh J, Granziera C, Killestein J, Bermel RA, Berge C, Kazlauskaite A, Schneble HM, Dahlke F, Cree BAC. Performance of Composite Endpoints Defining Progression Independent of Relapse Activity in Multiple Sclerosis. Ann Clin Transl Neurol. 2025 Sep;12(9):1805-1812. doi: 10.1002/acn3.70111. Epub 2025 Jul 8.
PubMed 40629721Kappos L, Yiu S, Dahlke F, Coetzee T, Cutter GR, Yuen S, Bonati U, Lublin FD. Composite Confirmed Disability Worsening/Progression Is a Useful Clinical Endpoint for Multiple Sclerosis Clinical Trials. Neurology. 2025 May 27;104(10):e213558. doi: 10.1212/WNL.0000000000213558. Epub 2025 Apr 21.
PubMed 40258203Hartung HP, Benedict RHB, Berger T, Bermel RA, Brochet B, Carroll WM, Freedman MS, Holmoy T, Karabudak R, Nos C, Patti F, Perrin Ross A, Vanopdenbosch L, Vollmer T, Wuerfel J, Clinch S, Kadner K, Kuenzel T, Kulyk I, Raposo C, Thanei GA, Killestein J. Ocrelizumab in Early-Stage Relapsing-Remitting Multiple Sclerosis: The Phase IIIb ENSEMBLE 4-Year, Single-Arm, Open-Label Trial. Neurology. 2024 Dec 24;103(12):e210049. doi: 10.1212/WNL.0000000000210049. Epub 2024 Dec 3.
PubMed 39626127Hartung HP, Berger T, Bermel RA, Brochet B, Carroll WM, Holmoy T, Karabudak R, Killestein J, Nos C, Patti F, Perrin Ross A, Vanopdenbosch L, Vollmer T, Buffels R, Garas M, Kadner K, Manfrini M, Wang Q, Freedman MS. ENSEMBLE PLUS: final results of shorter ocrelizumab infusion from a randomized controlled trial. J Neurol. 2024 Jul;271(7):4348-4360. doi: 10.1007/s00415-024-12326-z. Epub 2024 Apr 22.
PubMed 38649522Hartung HP; ENSEMBLE Steering Committee members and study investigators. Ocrelizumab shorter infusion: Primary results from the ENSEMBLE PLUS substudy in patients with MS. Neurol Neuroimmunol Neuroinflamm. 2020 Jun 4;7(5):e807. doi: 10.1212/NXI.0000000000000807. Print 2020 Sep.
PubMed 32503093