A Study to Evaluate the Efficacy and Safety of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

NCT ID: NCT04035005

Last Updated: 2025-08-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 1013 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-08-12
• Study Completion Date: 2028-01-19

Brief Summary

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).

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phase at the time of the primary analysis and will not enter the OLE phase; participants who have completed or withdrawn from the OLE phase or from PDP OCR treatment phase.

Conditions

Multiple Sclerosis, Primary Progressive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Ocrelizumab

Participants will receive ocrelizumab by intravenous (IV) infusion every 24 weeks.

Group Type: EXPERIMENTAL

Ocrelizumab

Intervention Type: DRUG

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.

Placebo

Participants will receive placebo matched to ocrelizumab by IV infusion every 24 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Ocrevus

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 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

Multiple Sclerosis Center of California

Laguna Hills, California, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

MS and Neuromuscular Center of Excellence

Clearwater, Florida, United States

Neurological Services of Orlando

Orlando, Florida, United States

Vero Neurology

Vero Beach, Florida, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Michigan Neurology Associates P.C.

Clinton Township, Michigan, United States

The Boster Center for MS

Columbus, Ohio, United States

Columbus Neuroscience

Westerville, Ohio, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Maxine Mesinger MS Clinic/Baylor College of Medicine

Houston, Texas, United States

Brain and Mind Research Institute

Camperdown, New South Wales, Australia

Austin Hospital

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

UZ Antwerpen

Edegem, Antwerpen, Belgium

Cliniques Universitaires St-Luc

Brussels, , Belgium

MS & Neurologisch Revalidatie Centrum

Overpelt, , Belgium

Military Medical Academy HBAT

Pleven, , Bulgaria

Multiprofile Hospital For Active Treatment Avis Medica

Pleven, , Bulgaria

Multiprofile Hospital for Active Treatment of Neurology and Psychiatry Sv. Naum EAD

Sofia, , Bulgaria

University of Alberta

Edmonton, Alberta, Canada

Dalhousie Multiple Sclerosis Research Unit

Halifax, Nova Scotia, Canada

St. Michael's Hospital

Toronto, Ontario, Canada

Recherche Sepmus Inc.

Greenfield Park, Quebec, Canada

Instituto Neurologico de Colombia INDEC

Medellín, Antioquia, Colombia

Clinica Colsanitas S.A. sede Clinica Universitaria Colombia

Bogotá, , Colombia

Clinical Hospital Centre Osijek

Osijek, , Croatia

General Hospital Varazdin

Varaždin, , Croatia

Clinical Hospital Sestre Milosrdnice

Zagreb, , Croatia

University Hospital Center Zagreb

Zagreb, , Croatia

CHU de Bordeaux - Hôpital Pellegrin

Bordeaux, , France

Centre Hospitalier Universitaire de Clermont Ferrand

Clermont-Ferrand, , France

CHRU Nancy

Nancy, , France

Hopital Guillaume Et Rene Laennec

Nantes, , France

CHU de Nimes - Hopital Universitaire Caremeau

Nîmes, , France

Hopital Civil

Strasbourg, , France

Pineo Medical Ecosystem LTD

Tbilisi, , Georgia

The First University Clinic of Tbilisi State Medical University

Tbilisi, , Georgia

Khechinashvili University Hospital

Tbilisi, , Georgia

AOU dell Universita degli Studi della Campania Luigi Vanvitelli Piazza Luigi Miraglia 2

Napoli, Campania, Italy

Fondazione PTV Policlinico Tor Vergata

Rome, Lazio, Italy

Azienda Ospedaliera Sant'andrea

Rome, Lazio, Italy

IRCCS Ospedale Policlinico San Martino

Genoa, Liguria, Italy

Ospedale San Raffaele S.r.l. - PPDS

Milan, Lombardy, Italy

Fondazione Istituto Neurologico Mondino IRCCS

Pavia, Lombardy, Italy

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, Piedmont, Italy

Fondazione Istituto G. Giglio di Cefalu

Cefalù, Sicily, Italy

Hotel Dieu de France

Achrafieh Beirut, , Lebanon

Saint George University Medical Hospital

El Achrafiyé, , Lebanon

Grupo Medico Camino

Mexico City, Mexico CITY (federal District), Mexico

Neurociencias Estudios Clinicos S.C.

Culiacán, Sinaloa, Mexico

Hospital Angeles Chihuahua

Chihuahua City, , Mexico

Unidad de Investigacion en Salud de Chihuahua

Mexico City, , Mexico

Clinical Research Institute

Tlalnepantla, , Mexico

CHU Mohammed VI

Marrakesh, , Morocco

Centre Hospitalier Ibn Sina CHIS - Hopital des Specialites

Rabat, , Morocco

New Zealand Clinical Research - Christchurch

Christchurch, , New Zealand

Dunedin Hospital

Dunedin, , New Zealand

Neurocentrum Bydgoszcz sp z o.o

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland

Przychodnia EuroMediCare

Wroclaw, Lower Silesian Voivodeship, Poland

Rejdak Konrad Indywidualna Praktyka Lekarska dr hab. Konrad Rejdak

Lublin, Lublin Voivodeship, Poland

Centrum Medyczne Medyk

Rzeszów, Podkarpackie Voivodeship, Poland

SPZOZ Wojewodzki Szpital Specjalistyczny nr 3

Rybnik, Silesian Voivodeship, Poland

Uniwersytecki Szpital Kliniczny w Bialymstoku Marii Sklodowskiej Curie 24a

Bia?ystok, , Poland

Copernicus Podmiot Leczniczy Sp z o o

Gda?sk, , Poland

Mazowieckie Centrum Badan Klinicznych

Grodzisk Mazowiecki, , Poland

MA-LEK Clinical Sp. Z o.o.

Katowice, , Poland

Novo-Med Zielinski i wsp SpJ

Katowice, , Poland

NEURO-MEDIC Sp. z o. o.

Katowice, , Poland

Specjalistyczna Praktyka Lekarska Dr n.med. Stanislaw Ochudlo

Katowice, , Poland

Szpital Uniwersytecki w Krakowie

Krakow, , Poland

Centrum Neurologii Krzysztof Selmaj

Lodz, , Poland

Galen Clinic

Lublin, , Poland

Wojewodzki Szpital Specjalistyczny

Olsztyn, , Poland

Med-Polonia Sp. z o.o.

Poznan, , Poland

EUROMEDIS Sp z o o

Szczecin, , Poland

Centrum Medyczne NeuroProtect Zablocinska 10

Warsaw, , Poland

RESMEDICA Spolka z o.o.

Kielce, Świętokrzyskie Voivodeship, Poland

ULS de Loures-Odivelas, EPE - Hospital de Loures

Loures, Lisbon District, Portugal

Hospital Garcia de Orta

Almada, , Portugal

Hospital de Braga

Braga, , Portugal

Hospital de Santo Antonio

Porto, , Portugal

Campus Neurologico Senior

Torres Vedras, , Portugal

Spitalul Judetean de Urgenta Deva

Deva, Hunedoara County, Romania

SC Clubul Sanatatii SRL

Campulung Muscel, , Romania

Cai Ferate Clinical Hospital

Constanța, , Romania

Targu Mures Clinical Emergency County Hospital

Târgu Mure?, , Romania

Krasnoyarsk State Medical Academy

Krasnoyarsk, Krasnoyarsk Krai, Russia

City Clinical Hospital a n Buyanov V M

Moscow, Moscow Oblast, Russia

City Clinical Hospital #24

Moscow, Moscow Oblast, Russia

Moscow Regional Research Clinical Institute Na Mfvladimirskiy

Moscow, Moscow Oblast, Russia

Research Center of Neurology of RAMS

Moskva, Moscow Oblast, Russia

Neftyanik Medical and Sanitary Unit

Tumen, Moscow Oblast, Russia

Nizhegorodskaya Regional Clinical Hospital n.a. Semashko

Nizhny Novgorod, Niznij Novgorod, Russia

MEDIS Limited Liability Company

Nizhny Novgorod, Niznij Novgorod, Russia

SBHI of Nizhny Novgorod region City Clinical Hospital #3

Nizhny Novgorod, Niznij Novgorod, Russia

National Center of Socially Significant Diseases

Saint Petersburg, Sankt-Peterburg, Russia

City Hospital #40 of Kurortniy Administrative District

Saint Petersburg, Sankt-Peterburg, Russia

City Clinical Hospital #4

Saransk, Saratov Oblast, Russia

Sverdlovsk Regional Clinical Hospital 1

Yekaterinburg, Sverdlovsk Oblast, Russia

Vertebronevrologiya LLC

Kazan', Tatarstan Republic, Russia

Ulyanovsk Regional Clinical Hospital

Ulyanovsk, Ulyanovsk Oblast, Russia

Belyayev Clinical Hospital of the Kuzbass

Kemerovo, , Russia

Kirov State Medical Academy

Kirov, , Russia

FSBIH Siberian Regional Medical Centre of FMBA of Russia

Novosibirsk, , Russia

Perm Regional Clinical Hospital of Znak Pocheta Medal

Perm, , Russia

Siberian State Medical University of Roszdrav

Tomsk, , Russia

Military Medical Academy

Belgrade, , Serbia

University Clinical Center of Serbia -PPDS

Belgrade, , Serbia

Clinical Hospital Centre Zemun

Belgrade, , Serbia

University Clinical Center Kragujevac

Kragujevac, , Serbia

Clinical Center Nis

Niš, , Serbia

Clinical Centre of Vojvodina

Nova Sad, , Serbia

General Hospital Uzice

Užice, , Serbia

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital Universitario Virgen de La Arrixaca

El Palmar, Murcia, Spain

Complejo Hospitalario Universitario de Vigo

Vigo, Pontevedra, Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Madrid, , Spain

Complejo Asistencial Universitario de Salamanca ? H. Clinico

Salamanca, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Hopital Razi

LA Mannouba, , Tunisia

Fattouma Bourguiba University Hospital

Monastir, , Tunisia

Hospital Habib Bourguiba

Sfax, , Tunisia

Military Hospital of Tunis

Tunis, , Tunisia

Treatment and diagnostic Center Neuro Global of LLC Neuro Global

Krykhivtsi, Ivano-Frankivsk Oblast, Ukraine

Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

Lviv, Kharkiv Governorate, Ukraine

Municipal Non-profit Enterprise Kherson City Clinical Hospital named after Ye.Ye. Karabelesh

Kherson, Kherson Governorate, Ukraine

Treatment and Diagnostic Center of LLC MRT Elit

Kropyvnytskyi, KIEV Governorate, Ukraine

Medical Centre of PE First Private Clinic

Kyiv, KIEV Governorate, Ukraine

Kyiv City Clinical Hospital #4

Kyiv, KIEV Governorate, Ukraine

Communal Non-Commercial Enterprise Clinical Hospital #15 of the Podilskyi District ofthe Kyiv City

Kyiv, KIEV Governorate, Ukraine

Municipal NPE Regional Clinical Center of Neurosurgery and Neurology of Transcarpathian RC

Uzhhorod, KIEV Governorate, Ukraine

Medical Center Artes Medicum LLC

Kyiv, Kyiv Oblast, Ukraine

Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

Lviv, Lviv Oblast, Ukraine

Medical Center Salutem

Vinnytsia, Podolia Governorate, Ukraine

LLC Medical Center Health Clinic

Vinnytsia, Volhynian Governorate, Ukraine

LLC Medical Center Unimed

Zaporizhzhia, Zaporizhzhia Oblast, Ukraine

University hospital of Dnipro State Medical University

Dnipro, , Ukraine

LLC Medical Center Family Medicine Clinic

Dnipro, , Ukraine

Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital

Kharkiv, , Ukraine

Medical Center of LLC Medical Center Dopomoga Plus

Kyiv, , Ukraine

Private Enterprise Clinic Medicom

Kyiv, , Ukraine

Volyn Regional Clinical Hospital

Lutsk, , Ukraine

LLC Medical Center INET 09

Zaporizhzhia, , Ukraine

Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council

Zaporizhzhia, , Ukraine

University Hospital of Wales

Cardiff, , United Kingdom

Queen Elizabeth University Hospital - PPDS

Glasgow, , United Kingdom

Raigmore Hospital - PPDS

Inverness, , United Kingdom

The Royal London Hospital

London, , United Kingdom

The National Hospital for Neurology & Neurosurgery

London, GT LON, , United Kingdom

University of Nottingham

Nottingham, , United Kingdom

Peninsula College of Medicine and Dentistry

Plymouth, , United Kingdom

Salford Royal Hospital

Salford, , United Kingdom

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Morriston Hospital

Swansea, , United Kingdom

Countries

United States; Australia; Belgium; Bulgaria; Canada; Colombia; Croatia; France; Georgia; Italy; Lebanon; Mexico; Morocco; New Zealand; Poland; Portugal; Romania; Russia; Serbia; Spain; Tunisia; Ukraine; United Kingdom

Other Identifiers

2018-001511-73

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-505980-36-00

Identifier Type: CTIS

Identifier Source: secondary_id

WA40404

Identifier Type: -

Identifier Source: org_study_id