A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (O'HAND)

February 4, 2026 updated by: Hoffmann-La Roche

A Phase IIIb Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

This study will evaluate the efficacy and safety of ocrelizumab (Ocrevus®) compared with placebo in participants with primary progressive multiple sclerosis (PPMS), including participants later in their disease course. This study will consist of the following phases: screening, double-blind treatment, an optional post-double-progression ocrelizumab (PDP OCR) treatment, follow-up 1 (FU1), an optional open-label extension (OLE), and follow-up 2 (FU2).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The screening phase will last up to 24 weeks. In the double-blind treatment phase, participants will undergo at least 144 weeks of study treatment. Study drug (ocrelizumab or placebo) will be administered every 24 weeks. All participants who discontinue prematurely from the double-blind treatment phase will enter the FU1 phase, including participants receiving other immunomodulatory or immunosuppressive treatment(s) for MS, commercial ocrelizumab, or no treatment. The FU1 phase will run in parallel with the double-blind treatment phase for 144 weeks or until the primary analysis is performed, whichever occurs first. An optional OLE phase is planned for eligible participants who either have either completed 144 weeks of the double-blind treatment phase or are ongoing in the double-blind treatment phase at the time of the primary analysis and, in the opinion of the investigator, could benefit from ocrelizumab treatment. The following participants will move into the FU2 phase: participants who are ongoing in the FU1 at 144 weeks from randomization or at the time of the primary analysis; participants who have either completed 144 weeks of the double-blind treatment phase or are ongoing in the double-blind treatment phase at the time of the primary analysis and will not enter the OLE phase; participants who have completed or withdrawn from the OLE phase or from PDP OCR treatment phase.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1013

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Brain and Mind Research Institute
    • Victoria
      • Heidelberg, Victoria, Australia, 3084
        • Austin Hospital
      • Parkville, Victoria, Australia, 3050
        • Royal Melbourne Hospital
  • Belgium
      • Brussels, Belgium, 1200
        • Cliniques Universitaires St-Luc
      • Overpelt, Belgium, 3900
        • MS & Neurologisch Revalidatie Centrum
    • Antwerpen
      • Edegem, Antwerpen, Belgium, 2650
        • UZ Antwerpen
  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Military Medical Academy HBAT
      • Pleven, Bulgaria, 5800
        • Multiprofile Hospital For Active Treatment Avis Medica
      • Sofia, Bulgaria, 1113
        • Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD
  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 2G3
        • University of Alberta
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 4K4
        • Dalhousie Multiple Sclerosis Research Unit
    • Ontario
      • Toronto, Ontario, Canada, M5B 1W8
        • St. Michael's Hospital
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2J2
        • Recherche Sepmus Inc.
  • Colombia
      • Bogotá, Colombia, 111321
        • Clinica Colsanitas S.A. sede Clinica Universitaria Colombia
    • Antioquia
      • Medellín, Antioquia, Colombia, 50012
        • Instituto Neurologico de Colombia INDEC
  • Croatia
      • Varaždin, Croatia, 42000
        • General Hospital Varazdin
      • Zagreb, Croatia, 10000
        • University Hospital Center Zagreb
      • Zagreb, Croatia, 10000
        • Clinical Hospital Sestre Milosrdnice
  • France
      • Bordeaux, France, 33076
        • CHU de Bordeaux - Hôpital Pellegrin
      • Clermont-Ferrand, France, 63003
        • Centre Hospitalier Universitaire de Clermont Ferrand
      • Nancy, France, 54035
        • Chru Nancy
      • Nantes, France, 44805
        • Hôpital Guillaume et René Laënnec
      • Nîmes, France, 30900
        • CHU de Nimes - Hopital Universitaire Caremeau
      • Strasbourg, France, 67098
        • Hôpital Civil
  • Georgia
      • Tbilisi, Georgia, 0114
        • Pineo Medical Ecosystem LTD
      • Tbilisi, Georgia, 0141
        • The First University Clinic of Tbilisi State Medical University
      • Tbilisi, Georgia, 179
        • Khechinashvili University Hospital
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80138
        • AOU dell Universita degli Studi della Campania Luigi Vanvitelli Piazza Luigi Miraglia 2
    • Lazio
      • Rome, Lazio, Italy, 00133
        • Fondazione PTV Policlinico Tor Vergata
      • Rome, Lazio, Italy, 00189
        • Azienda Ospedaliera Sant'Andrea
    • Liguria
      • Genoa, Liguria, Italy, 16132
        • IRCCS AOM Azienda Ospedaliera Metropolitana
    • Lombardy
      • Milan, Lombardy, Italy, 20132
        • Ospedale San Raffaele S.r.l. - PPDS
      • Pavia, Lombardy, Italy, 27100
        • Fondazione Istituto Neurologico Mondino IRCCS
    • Piedmont
      • Orbassano, Piedmont, Italy, 10043
        • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
    • Sicily
      • Cefalù, Sicily, Italy, 90015
        • Fondazione Istituto G. Giglio di Cefalu
  • Lebanon
      • Achrafieh Beirut, Lebanon, 000000
        • Hotel Dieu de France
      • El Achrafiyé, Lebanon, DUMMY_VALUE
        • Saint George University Medical Hospital
  • Mexico
      • Chihuahua City, Mexico, 31238
        • Hospital Angeles Chihuahua
      • Mexico City, Mexico, 14050
        • Unidad de Investigacion en Salud de Chihuahua
      • Tlalnepantla, Mexico, 54055
        • Clinical Research Institute
    • Mexico CITY (federal District)
      • Mexico City, Mexico CITY (federal District), Mexico, 03310
        • Grupo Medico Camino
    • Sinaloa
      • Culiacán, Sinaloa, Mexico, 80020
        • Neurociencias Estudios Clinicos S.C.
  • Morocco
      • Marrakesh, Morocco, 40080
        • CHU Mohammed VI
      • Rabat, Morocco, 10100
        • Centre Hospitalier Ibn Sina CHIS - Hopital des Specialites
  • New Zealand
      • Christchurch, New Zealand, 8011
        • New Zealand Clinical Research - Christchurch
      • Dunedin, New Zealand
        • Dunedin Hospital
  • Poland
      • Bia?ystok, Poland, 15-276
        • Uniwersytecki Szpital Kliniczny w Bialymstoku Marii Sklodowskiej Curie 24a
      • Gda?sk, Poland, 80-803
        • COPERNICUS Podmiot Leczniczy Sp z o o
      • Grodzisk Mazowiecki, Poland, 05-825
        • Mazowieckie Centrum Badan Klinicznych
      • Katowice, Poland, 40-584
        • Novo-Med Zielinski i wsp SpJ
      • Katowice, Poland, 40-571
        • MA-LEK Clinical Sp. z o.o.
      • Katowice, Poland, 40-686
        • NEURO-MEDIC Sp. z o. o.
      • Katowice, Poland, 40-752
        • Specjalistyczna Praktyka Lekarska Dr n.med. Stanislaw Ochudlo
      • Krakow, Poland, 31-503
        • Szpital Uniwersytecki w Krakowie
      • Lodz, Poland, 90-324
        • Centrum Neurologii Krzysztof Selmaj
      • Lublin, Poland, 20-064
        • Galen Clinic
      • Olsztyn, Poland, 10-561
        • Wojewodzki Szpital Specjalistyczny
      • Poznan, Poland, 60-693
        • Med-Polonia Sp. z o.o.
      • Szczecin, Poland, 70-215
        • EUROMEDIS Sp z o o
      • Warsaw, Poland, 01-684
        • Centrum Medyczne NeuroProtect Zablocinska 10
    • Kuyavian-Pomeranian Voivodeship
      • Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland, 85-796
        • Neurocentrum Bydgoszcz sp z o.o
    • Lower Silesian Voivodeship
      • Wroclaw, Lower Silesian Voivodeship, Poland, 50-220
        • Przychodnia EuroMediCare
    • Lublin Voivodeship
      • Lublin, Lublin Voivodeship, Poland, 20-410
        • Rejdak Konrad Indywidualna Praktyka Lekarska dr hab. Konrad Rejdak
    • Podkarpackie Voivodeship
      • Rzeszów, Podkarpackie Voivodeship, Poland, 35-055
        • Centrum Medyczne MEDYK
    • Silesian Voivodeship
      • Rybnik, Silesian Voivodeship, Poland, 44-200
        • SPZOZ Wojewodzki Szpital Specjalistyczny nr 3
    • Świętokrzyskie Voivodeship
      • Kielce, Świętokrzyskie Voivodeship, Poland, 25-726
        • RESMEDICA Spolka z o.o.
  • Portugal
      • Almada, Portugal, 2805-267
        • Hospital Garcia de Orta
      • Braga, Portugal, 4710-243
        • Hospital de Braga
      • Porto, Portugal, 4099-001
        • Hospital de Santo Antonio
      • Torres Vedras, Portugal, 2560-280
        • Campus Neurológico Sénior
    • Lisbon District
      • Loures, Lisbon District, Portugal, 2674-514
        • ULS de Loures-Odivelas, EPE - Hospital de Loures
  • Romania
      • Campulung Muscel, Romania, 115100
        • SC Clubul Sanatatii SRL
      • Constanța, Romania, 900123
        • Cai Ferate Clinical Hospital
      • Târgu Mure?, Romania, 540136
        • Targu Mures Clinical Emergency County Hospital
    • Hunedoara County
      • Deva, Hunedoara County, Romania, 330084
        • Spitalul Judetean de Urgenta Deva
  • Russia
      • Kemerovo, Russia, 650066
        • Belyayev Clinical Hospital of the Kuzbass
      • Kirov, Russia, 610027
        • Kirov State Medical Academy
      • Novosibirsk, Russia, 630007
        • FSBIH Siberian Regional Medical Centre of FMBA of Russia
      • Perm, Russia, 614990
        • Perm Regional Clinical Hospital of Znak Pocheta Medal
      • Tomsk, Russia, 634050
        • Siberian State Medical University of Roszdrav
    • Krasnoyarsk Krai
      • Krasnoyarsk, Krasnoyarsk Krai, Russia, 660022
        • Krasnoyarsk State Medical Academy
    • Moscow Oblast
      • Moscow, Moscow Oblast, Russia, 115516
        • City Clinical Hospital a n Buyanov V M
      • Moscow, Moscow Oblast, Russia, 127015
        • City Clinical Hospital #24
      • Moscow, Moscow Oblast, Russia, 129110
        • Moscow Regional Research Clinical Institute Na Mfvladimirskiy
      • Moskva, Moscow Oblast, Russia, 125367
        • Research Center of Neurology of RAMS
      • Tumen, Moscow Oblast, Russia, 625000
        • Neftyanik Medical and Sanitary Unit
    • Niznij Novgorod
      • Nizhny Novgorod, Niznij Novgorod, Russia, 603126
        • Nizhegorodskaya Regional Clinical Hospital n.a. Semashko
      • Nizhny Novgorod, Niznij Novgorod, Russia, 603137
        • MEDIS Limited Liability Company
      • Nizhny Novgorod, Niznij Novgorod, Russia, 603155
        • SBHI of Nizhny Novgorod region City Clinical Hospital #3
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russia, 197110
        • National Center of Socially Significant Diseases
      • Saint Petersburg, Sankt-Peterburg, Russia, 197706
        • City Hospital #40 of Kurortniy Administrative District
    • Saratov Oblast
      • Saransk, Saratov Oblast, Russia, 430032
        • City Clinical Hospital #4
    • Sverdlovsk Oblast
      • Yekaterinburg, Sverdlovsk Oblast, Russia, 620102
        • Sverdlovsk Regional Clinical Hospital 1
    • Tatarstan Republic
      • Kazan', Tatarstan Republic, Russia, 420043
        • Vertebronevrologiya LLC
    • Ulyanovsk Oblast
      • Ulyanovsk, Ulyanovsk Oblast, Russia, 432063
        • Ulyanovsk Regional Clinical Hospital
  • Serbia
      • Belgrade, Serbia, 11000
        • Military Medical Academy
      • Belgrade, Serbia, 11080
        • Clinical Hospital Centre Zemun
      • Belgrade, Serbia, 11000
        • University Clinical Center of Serbia -PPDS
      • Kragujevac, Serbia, 34000
        • University Clinical Center Kragujevac
      • Niš, Serbia, 18000
        • Clinical Center Nis
      • Nova Sad, Serbia, 21000
        • Clinical Centre of Vojvodina
      • Užice, Serbia, 31000
        • General Hospital Uzice
  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clinic de Barcelona
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro - Majadahonda
      • Salamanca, Spain, 37007
        • Complejo Asistencial Universitario de Salamanca ? H. Clinico
      • Seville, Spain, 41009
        • Hospital Universitario Virgen Macarena
      • Valencia, Spain, 46026
        • Hospital Universitari i Politecnic La Fe de Valencia
    • Madrid
      • Pozuelo de Alarcón, Madrid, Spain, 28223
        • Hospital Universitario Quirónsalud Madrid
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Universitario Virgen de La Arrixaca
    • Pontevedra
      • Vigo, Pontevedra, Spain, 36312
        • Complejo Hospitalario Universitario de Vigo
  • Tunisia
      • LA Mannouba, Tunisia, 2010
        • Hopital Razi
      • Monastir, Tunisia, 5000
        • Fattouma Bourguiba University Hospital
      • Sfax, Tunisia, 3029
        • Hospital Habib Bourguiba
      • Tunis, Tunisia, 1008
        • Military Hospital of Tunis
  • Ukraine
      • Dnipro, Ukraine, 49600
        • LLC Medical Center Family Medicine Clinic
      • Dnipro, Ukraine, 49089
        • University hospital of Dnipro State Medical University
      • Kharkiv, Ukraine, 61022
        • Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital
      • Kyiv, Ukraine, 02000
        • Medical Center of LLC Medical Center Dopomoga Plus
      • Kyiv, Ukraine, 04219
        • Private Enterprise Clinic Medicom
      • Lutsk, Ukraine, 43005
        • Volyn Regional Clinical Hospital
      • Zaporizhzhia, Ukraine, 69600
        • Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
      • Zaporizhzhia, Ukraine, 69035
        • LLC Medical Center INET 09
    • Ivano-Frankivsk Oblast
      • Krykhivtsi, Ivano-Frankivsk Oblast, Ukraine, 76493
        • Treatment and diagnostic Center Neuro Global of LLC Neuro Global
    • KIEV Governorate
      • Kropyvnytskyi, KIEV Governorate, Ukraine, 25005
        • Treatment and Diagnostic Center of LLC MRT Elit
      • Kyiv, KIEV Governorate, Ukraine, 03037
        • Medical Centre of PE First Private Clinic
      • Kyiv, KIEV Governorate, Ukraine, 03110
        • Kyiv City Clinical Hospital #4
      • Kyiv, KIEV Governorate, Ukraine, 04070
        • Communal Non-Commercial Enterprise Clinical Hospital #15 of the Podilskyi District ofthe Kyiv City
      • Uzhhorod, KIEV Governorate, Ukraine, 88018
        • Municipal NPE Regional Clinical Center of Neurosurgery and Neurology of Transcarpathian RC
    • Kharkiv Governorate
      • Lviv, Kharkiv Governorate, Ukraine, 79010
        • Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
    • Kherson Governorate
      • Kherson, Kherson Governorate, Ukraine, 73000
        • Municipal Non-profit Enterprise Kherson City Clinical Hospital named after Ye.Ye. Karabelesh
    • Kyiv Oblast
      • Kyiv, Kyiv Oblast, Ukraine, 02002
        • Medical Center Artes Medicum LLC
    • Lviv Oblast
      • Lviv, Lviv Oblast, Ukraine, 79010
        • Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital
    • Podolia Governorate
      • Vinnytsia, Podolia Governorate, Ukraine, 21009
        • Medical Center Salutem
    • Volhynian Governorate
      • Vinnytsia, Volhynian Governorate, Ukraine, 21009
        • LLC Medical Center Health Clinic
    • Zaporizhzhia Oblast
      • Zaporizhzhia, Zaporizhzhia Oblast, Ukraine, 69000
        • LLC Medical Center Unimed
  • United Kingdom
      • Cardiff, United Kingdom, CF14 4XW
        • University Hospital of Wales
      • Glasgow, United Kingdom, G51 4TF
        • Queen Elizabeth University Hospital - PPDS
      • Inverness, United Kingdom, IV2 3JH
        • Raigmore Hospital - PPDS
      • London, United Kingdom, E1 1BB
        • The Royal London Hospital
      • London, GT LON, United Kingdom, WC1N 3BG
        • The National Hospital for Neurology & Neurosurgery
      • Nottingham, United Kingdom, NG7 2UH
        • University of Nottingham
      • Plymouth, United Kingdom, PL6 8BX
        • Peninsula College of Medicine and Dentistry
      • Salford, United Kingdom, M6 8HD
        • Salford Royal Hospital
      • Sheffield, United Kingdom, S10 2JF
        • Royal Hallamshire Hospital
      • Swansea, United Kingdom, SA6 6NL
        • Morriston Hospital
  • United States
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20007
        • Georgetown University Medical Center
    • Florida
      • Clearwater, Florida, United States, 33761
        • MS and Neuromuscular Center of Excellence
      • Orlando, Florida, United States, 32806
        • Neurological Services of Orlando
      • Vero Beach, Florida, United States, 32960
        • Vero Neurology
    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43235-5422
        • The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company
      • Westerville, Ohio, United States, 43082-6910
        • Columbus Neuroscience
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19141
        • Albert Einstein Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • EDSS score at screening and baseline >= 3.0 to 8.0, inclusive
  • Disease duration from the onset of MS symptoms relative to randomization date:

Less than 20 years in participants with an EDSS score at screening 7.0 - 8.0 Less than 15 years in participants with an EDSS at screening 5.5 - 6.5 Less than 10 years in participants with an EDSS at screening <= 5.0

  • Documented history or presence at screening of at least one of the following laboratory findings in a cerebrospinal fluid specimen: Elevated immunoglobulin G (IgG) index or one or more IgG oligoclonal bands detected by isoelectric focusing
  • Screening and baseline 9-HPT completed in > 25 seconds (average of the two hands)
  • Neurological stability for ≥ 30 days prior to baseline
  • Ability to complete the 9-HPT within 240 seconds with each hand at screening and baseline
  • Neurological stability for >/= 30 days prior to baseline
  • Participants previously treated with immunosuppressants, immunomodulators, or other immunomodulatory therapies must undergo an appropriate washout period according to the local label of the immunosuppressant/immunomodulatory drug used
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
  • For female participants without reproductive potential: Women may be enrolled if surgically sterile (i.e hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile

Exclusion Criteria:

  • History of relapsing-remitting or secondary progressive MS at screening
  • Confirmed serious opportunistic infection including: active bacterial, viral, fungal, mycobacterial infection or other infection, including tuberculosis or atypical mycobacterial disease
  • Participants who have or have had confirmed or a high degree of suspicion of progressive multifocal leukoencephalopathy (PML)
  • Known active malignancy or are being actively monitored for recurrence of malignancy
  • Immunocompromised state
  • Receipt of a live-attenuated vaccine within 6 weeks prior to randomization
  • Inability to complete an MRI or contraindication to Gd administration.
  • Participants requiring symptomatic treatment of MS and/or physiotherapy who are not on a stable regimen. Participants must not initiate symptomatic treatment of MS or physiotherapy within 4 weeks of randomization.
  • Contraindications to mandatory premedications for infusion-related reactions, including:

uncontrolled psychosis for corticosteroids and closed-angle glaucoma for antihistamines

  • Known presence of other neurologic disorders
  • Pregnant or breastfeeding, or intending to become pregnant during the study and for 6 or 12 months after last infusion of the study drug
  • Lack of peripheral venous access
  • Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal, or any other significant disease that may preclude participant from participating in the study
  • Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
  • History of alcohol or other drug abuse
  • History of primary or secondary immunodeficiency
  • Treatment with any investigational agent within 24 weeks prior to screening (Visit 1) or 5 half-lives of the investigational drug (whichever is longer), or treatment with any experimental procedure for MS
  • Previous treatment with B-cell targeting therapies
  • Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
  • Any previous history of transplantation or anti-rejection therapy
  • Treatment with IV Ig or plasmapheresis within 12 weeks prior to randomization
  • Systemic corticosteroid therapy within 4 weeks prior to screening
  • Positive serum human chorionic gonadotropin (hCG) measured at screening or positive urine β-hCG at baseline
  • Positive screening tests for hepatitis B
  • Any additional exclusionary criterion as per ocrelizumab (Ocrevus®) local label, if more stringent than the above
  • Lack of MRI activity at screening/baseline if more than 650 participants without MRI activity have already been enrolled, as defined by T1 Gd+ lesion(s) and/or new and/or enlarged T2 lesion(s) in the screening, to ensure that at least 350 participants with MRI activity will be randomized

Eligibility Criteria for OLE Phase:

  • Completed the 144 weeks of double-blind treatment phase of the trial or are ongoing in the double blind treatment phase at the time of the primary analysis, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Participants who withdrew from study treatment and received another DMT or commercial ocrelizumab will not be allowed to enter in the OLE phase.
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use adequate contraceptive methods during the treatment period and for 6 or 12 months after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required.
  • For female participants without reproductive potential: Women may be enrolled if surgically sterile (i.e. hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the participant is receiving a hormonal therapy for her menopause or if surgically sterile

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Participants will receive placebo matched to ocrelizumab by IV infusion every 24 weeks.
Drug: Placebo
The first dose of placebo will be administered as two IV infusions given 14 days apart. For the subsequent doses, placebo will be administered as a single infusion every 24 weeks, with a minimum interval of 20 or 22 weeks, depending on if the previous dose was administered in one or two infusions, maintained between each infusion.
Experimental: Ocrelizumab
Participants will receive ocrelizumab by intravenous (IV) infusion every 24 weeks.
Drug: Ocrelizumab
The first dose of ocrelizumab will be administered as two 300 milligrams (mg), IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg infusion every 24 weeks. A minimum interval of 20 or 22 weeks, depending on if the previous dose was administered in one or two infusion, should be maintained between each infusion.
Other Names:
  • Ocrevus

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) in FAS
Time Frame: Up to approximately 243 weeks
Time to onset of cCDP12=time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-hole Peg Test (9-HPT) confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in Expanded Disability Status Scale (EDSS) score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of >5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems & ambulation, that ranges in 0.5-point steps from 0 [normal] to 10.0 [death]. 9-HPT is a quantitative measure of arm & hand function, where participants placed & removed pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
Up to approximately 243 weeks
Time to Onset of cCDP12 in Magnetic Resonance Imaging (MRI) Activity Analysis Set
Time Frame: Up to approximately 243 weeks
Time to onset of cCDP12 was defined as the time from randomization to the first occurrence of at least one of the following progression events: 1) 20% worsening from baseline in 9-HPT confirmed for at least 12 weeks; 2) increase of ≥ 1.0 point from baseline in EDSS score in participants with a baseline EDSS score ≤5.5 or an increase of ≥ 0.5 point in participants with a baseline EDSS score of >5.5 that is confirmed for at least 12 weeks. EDSS disability scale is based on a standard neurological examination, incorporating functional systems & ambulation, that ranges in 0.5-point steps from 0 [normal] to 10.0 [death]. 9-HPT is a quantitative measure of arm & hand function, where participants placed & removed pegs 1 by 1 into 9 holes arranged in a board & complete 2 successful trials for each hand & the total time (in seconds) required was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
Up to approximately 243 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to 12-week CDP in 9-HPT
Time Frame: Up to approximately 243 weeks
12-week CDP in 9-HPT was defined as a 20% worsening from baseline in 9-HPT confirmed for at least 12 weeks. 9-HPT is a quantitative measure of upper extremity (arm and hand) function. The test device consists of a container containing nine pegs and a wood or plastic block containing nine empty holes. Participants were required to pick up each of the 9 pegs one at a time and place them in the 9 holes. Once all the pegs were in the holes, the participants then removed them as quickly as possible. Both dominant and non-dominant hands were tested twice, and the total time (in seconds) to complete the task was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
Up to approximately 243 weeks
Time to 12-week CDP in EDSS
Time Frame: Up to approximately 243 weeks
12-week CDP in EDSS=an increase of ≥1.0 point from baseline EDSS score in participants with a baseline EDSS score of ≤5.5 or an increase of ≥0.5 points in participants with a baseline EDSS score of <5.5 that is confirmed for at least 12 weeks after initial documentation of the progression. EDSS was used to measure changes in the disability level of participants with MS over time. EDSS is based on a standard neurological examination, incorporating functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel & bladder, & cerebral [or mental]) that are rated & then scored as a functional system scores (FSS), & ambulation, which is scored as ambulation score. Each FSS is an ordinal clinical rating scale where score ranges from 0-5/6, & ambulation score that is rated from 0 to 16. These ratings along with observations & assistive devices were then used to determine the total EDSS score. The total EDSS score ranges from 0 (normal) to 10.0 (death) in 0.5-point steps.
Up to approximately 243 weeks
Time to 24-week CDP in 9-HPT
Time Frame: Up to approximately 243 weeks
24-week CDP in 9-HPT was defined as a 20% worsening from baseline in 9-HPT confirmed for at least 24 weeks. 9-HPT is a quantitative measure of upper extremity (arm and hand) function. The test device consists of a container containing nine pegs and a wood or plastic block containing nine empty holes. Participants were required to pick up each of the 9 pegs one at a time and place them in the 9 holes. Once all the pegs were in the holes, the participants then removed them as quickly as possible. Both dominant and non-dominant hands were tested twice, and the amount of time (in seconds) to complete the task was recorded. The longer it took to complete the test, the higher the scores, indicating deterioration.
Up to approximately 243 weeks
Time to 24-week CDP in EDSS
Time Frame: Up to approximately 243 weeks
24-week CDP in EDSS=an increase of ≥1.0 point from baseline EDSS score in participants with a baseline EDSS score of ≤5.5 or an increase of ≥0.5 points in participants with a baseline EDSS score of <5.5 that is confirmed for at least 24 weeks after initial documentation of the progression. EDSS was used to measure changes in the disability level of participants with MS over time. EDSS is based on a standard neurological examination, incorporating functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel & bladder, & cerebral [or mental]) that are rated and then scored as a FSS, and ambulation, which is scored as ambulation score. Each FSS is an ordinal clinical rating scale where score ranges from 0 to 5 or 6, and ambulation score that is rated from 0 to 16. These ratings along with observations and assistive devices were then used to determine the total EDSS score. The total EDSS score ranges from 0 (normal) to 10.0 (death) in 0.5-point steps.
Up to approximately 243 weeks
Annual Rate of Change From Baseline in Radius of Total Volume of T2 Lesions
Time Frame: Up to approximately 120 weeks
Volume of T2 lesions was measured using MRI scans. Mean difference in annual rate of change from baseline in radius of total volume of T2 lesions between the ocrelizumab and placebo arms in participants with PPMS, including participants later in their disease course, where no treatment discontinuation nor initiation of alternative MS disease-modifying treatment (DMT) or commercial ocrelizumab occurred, is reported. Random Coefficient Regression (RCRM) Model was used to estimate annual rate of change.
Up to approximately 120 weeks
Annual Rate of Percent Change From Week 24 in Total Brain Volume
Time Frame: From Week 24 up to approximately 120 weeks
Brain volume was measured using MRI scans. Mean difference in annual rate of percent change from Week 24 in total brain volume between the ocrelizumab and placebo arms in participants with PPMS, including participants later in their disease course, where no treatment discontinuation nor initiation of alternative MS DMT or commercial ocrelizumab occurred, is reported. RCRM Model was used to estimate annual rate of change.
From Week 24 up to approximately 120 weeks
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: From initiation of study drug up to approximately 10.5 years
AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is any AE that is: Fatal; Life-threatening; Requires or prolongs inpatient hospitalization; Results in persistent or significant disability/incapacity; A congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study drug OR a significant medical event in the investigator's judgment.
From initiation of study drug up to approximately 10.5 years
Serum Concentration of Ocrelizumab
Time Frame: Up to approximately 10.5 years
Up to approximately 10.5 years
B-cell Levels in Blood
Time Frame: Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Change From Baseline in B-cell Levels
Time Frame: Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Percentage of Participants With B-cell Counts ≤5 Cells/μL
Time Frame: Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Percentages have been rounded off.
Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Percentage of Participants With B-cell Counts ≤10 Cells/μL
Time Frame: Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Percentages have been rounded off.
Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228
Number of Participants With ADAs to Ocrelizumab
Time Frame: Baseline up to approximately 10.5 years
Prevalence of ADAs at baseline is defined as the number of participants that is ADA positive at baseline. For determining post-baseline incidence, participants are considered to be ADA-positive if they are ADA-negative or have missing data at baseline but develop an ADA response following study drug exposure, or if they are ADA-positive at baseline and the titer of 1 or more post-baseline samples is at least 0.60 titer unit (t.u.) greater than the baseline titer result.
Baseline up to approximately 10.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 12, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 15, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 19, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 17, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 29, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 23, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • WA40404
  • 2018-001511-73 (EudraCT Number)
  • 2023-505980-36-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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