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

Multiple Sclerosis, Primary Progressive Clinical Trial

— O'HAND  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04035005
• Other study ID #: WA40404
• Status: Recruiting
• Phase: Phase 3
• Start date: August 12, 2019
• Est. completion date: November 11, 2030

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: WA40404 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 focuses on upper limit disability progression. This study will consist of the following phases: screening, double-blind treatment, follow-up 1 (FU1), an optional open-label extension (OLE), follow-up 2 (FU2), and B-cell monitoring (BCM).

Description:

The screening phase will last up to 24 weeks. In the double-blind treatment phase, participants will undergo at least 120 weeks of study treatment. Study drug (ocrelizumab or placebo) will be administered every 24 weeks. In the FU1 phase, all participants who discontinue prematurely from the double-blind treatment phase will enter the FU1 phase, including participants who receive post-double progression ocrelizumab (PDP OCR) treatment, 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 until the primary analysis is performed. If the primary analysis is positive, an optional OLE phase is planned for eligible participants who either have remained in the double-blind treatment phase or are on PDP OCR treatment at the time of the primary analysis and, in the opinion of the investigator, could benefit from ocrelizumab treatment. The follow-up 2 (FU2) phase will begin after the primary analysis is performed. The following participants will move into the FU2 phase: participants who are ongoing in the FU1 and not on PDP OCR treatment at the time of primary analysis; participants who are ongoing in the double-blind treatment phase or receiving PDP OCR at the time of the primary analysis and do not enter the OLE phase; participants who complete or withdraw from the OLE phase. At the end of the FU2, all participants will move into B-cell monitoring (BCM) phase until the end of the study. This study will end when all participants who are not being treated with an alternative B-cell depleting therapy have repleted his or her B-cells.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: November 11, 2030
• Est. primary completion date: December 10, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 patients with an EDSS score at screening 7.0 - 8.0 Less than 15 years in patients with an EDSS at screening 5.5 - 6.5 Less than 10 years in patients 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 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

• Patients 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 patients without reproductive potential: Women may be enrolled if surgically sterile (i.e hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the patient 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

• Patients 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.

• Patients requiring symptomatic treatment of MS and/or physiotherapy who are not on a stable regimen. Patients 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 patient 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 hCG measured at screening or positive urine ß-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 patients 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 patients with MRI activity will be randomized

Eligibility Criteria for Open-Label Extension Phase:

• Completed the double-blind treatment phase of the trial or have received PDP OCR in the FU1 phase, and who, in the opinion of the investigator, may benefit from treatment with Ocrelizumab. Patients who withdrew from study treatment and received another disease-modifying therapy (DMT) or commercial ocrelizumab will not be allowed to enter in the OLE phase.

• Meet the re-treatment criteria for ocrelizumab

• 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 patients without reproductive potential: Women may be enrolled if surgically sterile (i.e. hysterectomy, complete bilateral oophorectomy) or post-menopausal unless the patient is receiving a hormonal therapy for her menopause or if surgically sterile

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Multiple Sclerosis, Primary Progressive
• Sclerosis

Intervention

Drug:
• Ocrelizumab
The first dose of ocrelizumab will be administered as two 300 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 if the previous dose was administered in one or two infusion, should be maintained between each infusion.
• Placebo
The first dose of placebo will be administered as two 300 mg IV infusions given 14 days apart. For the subsequent doses, placebo will be administered as a single 600 mg infusion every 24 weeks, with a minimum interval of 20 or 22 weeks, depending if the previous dose was administered in one or two infusion, should be maintained between each infusion.

Locations

Country	Name	City	State
Australia	Brain and Mind Research Institute	Camperdown	New South Wales
Australia	Austin Hospital	Heidelberg	Victoria
Australia	John Hunter Hospital	New Lambton	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Austria	Kepler Universitatsklinikum Linz	Linz
Belgium	Cliniques Universitaires St-Luc	Bruxelles
Belgium	UZ Antwerpen PIN	Edegem
Belgium	CHU Tivoli	La Louvière
Belgium	MS & Neurologisch Revalidatie Centrum	Overpelt
Bulgaria	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
Canada	University of Alberta	Edmonton	Alberta
Canada	Clinique Neuro Outaouais	Gatineau	Quebec
Canada	Recherche Sepmus Inc.	Greenfield Park	Quebec
Canada	Dalhousie Multiple Sclerosis Research Unit	Halifax	Nova Scotia
Canada	London Health Sciences Centre	London	Ontario
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Colombia	Clinica Colsanitas S.A. sede Clinica Universitaria Colombia	Bogota, D.C.
Colombia	Instituto Neurologico de Colombia INDEC	Medellin
Croatia	Clinical Hospital Centre Osijek	Osijek
Croatia	General Hospital Varazdin	Varazdin
Croatia	Clinical Hospital Sestre Milosrdnice	Zagreb
Croatia	University Hospital Center Zagreb	Zagreb
Egypt	Ain Shams University Hospital	Cairo
France	CHU Amiens Hopital Sud; Neurologie	Amiens Cedex1
France	Centre Hospitalier Universitaire de Bordeaux Hopital Pellegrin	Bordeaux
France	Hopital Pierre Wertheimer	Cedex
France	Centre Hospitalier Universitaire de Clermont Ferrand	Clermont-ferrand
France	Centre Hospitalier de Colmar - Hopital Louis Pasteur; Service de Neurologie	Colmar
France	Hopitaux de La Timone	Marseille
France	CHU Gui de Chauliac	Montpellier
France	CHRU Nancy	Nancy
France	Hopital Guillaume Et Rene Laennec	Nantes
France	CHU de Nimes - Hopital Universitaire Caremeau	Nimes
France	Hopital Civil	Strasbourg
Georgia	Khechinashvili University Hospital	Tbilisi
Georgia	Pineo Medical Ecosystem LTD	Tbilisi
Georgia	Tbilisi State Medical University	Tbilisi
Germany	Medizinische Hochschule Hannover	Hannover
Hungary	Bacs-Kiskun Megyei Korhaz	Kecskemet
Hungary	Szent Borbala Korhaz	Tatabánya
Ireland	Saint Vincent's University Hospital	Dublin
Italy	Fondazione Istituto G. Giglio di Cefalu	Cefalù	Sicilia
Italy	Ospedale Policlinico San Martino	Genova	Liguria
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano	Lombardia
Italy	AOU dell Universita degli Studi della Campania Luigi Vanvitelli Piazza Luigi Miraglia 2	Napoli	Campania
Italy	Azienda Sanitaria Ospedaliera S Luigi Gonzaga	Orbassano	Piemonte
Italy	Fondazione Istituto Neurologico Mondino IRCCS	Pavia	Lombardia
Italy	Azienda Ospedaliera Sant'andrea	Rome	Lazio
Italy	Fondazione PTV Policlinico Tor Vergata	Rome	Lazio
Lebanon	Saint George University Medical Hospital	Achrafieh
Lebanon	American University of Beirut - Medical Center	Beirut
Lebanon	Hotel Dieu de France	Beirut
Mexico	Hospital Angeles Chihuahua	Chihuahua
Mexico	Scientia Investigacion Clinica S.C.	Chihuahua
Mexico	Neurociencias Estudios Clinicos S.C.	Culiacán	Sinaloa
Mexico	Grupo Medico Camino	DF	Mexico CITY (federal District)
Mexico	Instituto de Investigationes Clinicas para la Salud AC	Durango
Mexico	Centro de Diagnostico Neurofisiologico S.C	Mexico City	Mexico CITY (federal District)
Mexico	Unidad de Investigacion en Salud de Chihuahua	Mexico City	Mexico CITY (federal District)
Mexico	Clinical Associates in Research Therapeutics of Americas-Mexico CARTA-MEX	Monterrey
Mexico	Clinical Research Institute	Tlalnepantla de Baz	Mexico CITY (federal District)
Morocco	CHU Mohammed VI	Marrakech
Morocco	Centre Hospitalier Ibn Sina CHIS - Hopital des Specialites	Rabat
Morocco	Hopital Militaire d'Instruction Mohamed V	Rabat
New Zealand	New Zealand Clinical Research - Christchurch	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Waikato Hospital; Neurology	Hamilton
New Zealand	Wellington Hospital	Wellington
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku Marii Sklodowskiej Curie 24a	Bia?ystok
Poland	Neurocentrum Bydgoszcz sp z o.o	Bydgoszcz
Poland	COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny	Gdansk
Poland	Mazowieckie Centrum Badan Klinicznych	Grodzisk Mazowiecki
Poland	M.A. - LEK A. M. Maciejowscy SC. Centrum Terapii SM	Katowice
Poland	Neuro-Medic Janusz Zbrojkiewicz	Katowice
Poland	Novo-Med Zielinski i wspolnicy Sp. j.	Katowice
Poland	Specjalistyczna Praktyka Lekarska Dr n.med. Stanislaw Ochudlo	Katowice
Poland	RESMEDICA Spolka z o.o.	Kielce
Poland	SP ZOZ Szpital Uniwersytecki w Krakowie; Oddzial Kliniczny Kliniki Neurologii	Kraków
Poland	Centrum Neurologii Krzysztof Selmaj	Lodz
Poland	Prywatny Gabinet Lekarski Urszula Chyrchel-Paszkiewicz	Lublin
Poland	Rejdak Konrad Indywidualna Praktyka Lekarska dr hab. Konrad Rejdak	Lublin
Poland	Wojewodzki Szpital Specjalistyczny	Olsztyn
Poland	EMC Instytut Medyczny SA	Pozna?
Poland	Clinical Research Center Sp z o o	Poznan
Poland	Wojewódzki Szpital Specjalistyczny Nr 3	Rybnik
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	EUROMEDIS Sp z o o	Szczecin
Poland	Centrum Medyczne NeuroProtect Zablocinska 10	Warsaw
Poland	Instytut Psychiatrii i Neurologii II Klinika Neurologiczna	Warszawa
Portugal	Hospital Garcia de Orta	Almada
Portugal	Hospital de Braga	Braga
Portugal	Hospital Beatriz Angelo	Loures
Portugal	Hospital de Santo Antonio	Porto
Portugal	Campus Neurologico Senior	Torres Vedras
Romania	Colentina Clinical Hospital	Bucharest
Romania	Emergency University Hospital	Bucharest
Romania	SC Clubul Sanatatii SRL	Campulung
Romania	County Hospital Caracal	Caracal
Romania	Cai Ferate Clinical Hospital	Constan?a
Romania	Spitalul Municipal Dr.Alexandru Simionescu Hunedoara	Hunedoara
Romania	Targu Mures Clinical Emergency County Hospital	Targu Mures
Russian Federation	State Healthcare Institution Territorial Clinical Hospital	Barnaul	Altaj
Russian Federation	Belgorod Regional Clinical Hospital	Belgorod
Russian Federation	Vertebronevrologiya LLC	Kazan	Tatarstan
Russian Federation	Kemerovo Regional Clinical Hospital	Kemerovo
Russian Federation	Kirov State Medical Academy	Kirov
Russian Federation	Krasnoyarsk State Medical Academy	Krasnoyarsk	Krasnojarsk
Russian Federation	City Clinical Hospital #24	Moscow	Moskovskaja Oblast
Russian Federation	Moscow Regional Research Clinical Institute Na Mfvladimirskiy	Moscow	Moskovskaja Oblast
Russian Federation	Research Center of Neurology of RAMS	Moscow	Moskovskaja Oblast
Russian Federation	City Clinical Hospital #15 n.a. N.F. Filatov	Moskva	Moskovskaja Oblast
Russian Federation	City Out Patient Clinic For Rehabilitation Treatment #7	Moskva	Moskovskaja Oblast
Russian Federation	City Clinical Hospital #12	Nizhny Novgorod	Niznij Novgorod
Russian Federation	MEDIS Limited Liability Company	Nizhny Novgorod	Niznij Novgorod
Russian Federation	Nizhegorodskaya Regional Clinical Hospital n.a. Semashko	Nizhny Novgorod	Niznij Novgorod
Russian Federation	SBHI of Nizhny Novgorod region City Clinical Hospital #3; neurology department	Nizniy Novgorod
Russian Federation	FSBIH Siberian Regional Medical Centre of FMBA of Russia	Novosibirsk
Russian Federation	Perm SMA n.a. academ. E.A. Vagner	Perm
Russian Federation	City Center of MS Treatment based on Saint-Petersburg City Clinical Hospital #31	Sankt-peterburg	Sankt Petersburg
Russian Federation	City Clinical Hospital #4	Saransk	Saratov
Russian Federation	City Hospital #40 of Kurortniy Administrative District	St. Petersburg	Sankt Petersburg
Russian Federation	Siberian State Medical University of Roszdrav	Tomsk
Russian Federation	Neftyanik Medical and Sanitary Unit	Tumen	Moskovskaja Oblast
Russian Federation	Regional State Budget Institution of Healthcare Tver Regional Clinical Hospital	Tver
Russian Federation	Kuvatov Republican Clinical Hospital	UFA	Baskortostan
Russian Federation	Ulyanovsk Regional Clinical Hospital	Ulyanovsk	Uljanovsk
Russian Federation	Yaroslavl Clinical Hospital #8	Yaroslavl	Sankt Petersburg
Russian Federation	Sverdlovsk Regional Clinical Hospital 1	Yekaterinburg	Sverdlovsk
Serbia	Clinical Center of Serbia	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Clinical Center Nis	NIS
Serbia	Clinical Centre of Vojvodina	Nova Sad
Serbia	General Hospital Uzice	Uzice
Serbia	Clinical Hospital Centre Zemun	Zemun
Spain	Hospital Universitario Cruces	Barakaldo	Vizcaya
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital General de Castellon	Castellon
Spain	Hospital Universitario HM Sanchinarro-CIOCC	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Hospital Regional Universitario Carlos Haya	Malaga
Spain	Hospital Universitario Virgen de La Arrixaca	Murcia
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcón	Madrid
Spain	Complejo Asistencial Universitario de Salamanca ? H. Clinico	Salamanca
Spain	Hospital Universitario Virgen Macarena	Seville	Sevilla
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
Spain	Complejo Hospitalario Universitario de Vigo	Vigo	Pontevedra
Tunisia	Hopital Razi	Mannouba
Tunisia	Fattouma Bourguiba University Hospital	Monastir
Tunisia	Hospital Habib Bourguiba	Sfax
Tunisia	Military Hospital of Tunis	Tunis
Ukraine	LLC Medical Center Family Medicine Clinic	Dnipro	Kherson Governorate
Ukraine	Separated structural unit ?University clinic? of Dnipro State Medical University	Dnipro	Kharkiv Governorate
Ukraine	Communal Non-commercial Enterprise of Kharkiv Regional Council Regional Clinical Hospital	Kharkiv	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	Treatment and diagnostic Center Neuro Global of LLC Neuro Global	Krykhivtsi	Polissya Okruha
Ukraine	Communal Non-Commercial Enterprise Clinical Hospital #15 of the Podilskyi District ofthe Kyiv City	Kyiv	KIEV Governorate
Ukraine	Kyiv City Clinical Hospital #4	Kyiv
Ukraine	LLC Smart Medical Center	Kyiv	KIEV Governorate
Ukraine	Medical Center Dopomoga Plus	Kyiv	Chernihiv Governorate
Ukraine	Medical Center of LLC Medical Clinic Blagomed	Kyiv	KIEV Governorate
Ukraine	Municipal Institution of Kyiv Regional Council Kyiv Regional Clinical Hospital	Kyiv
Ukraine	Volyn Regional Clinical Hospital	Lutsk
Ukraine	Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital	Lviv	Kharkiv Governorate
Ukraine	Municipal NPE Regional Clinical Center of Neurosurgery and Neurology of Transcarpathian RC	Uzhhorod	KIEV Governorate
Ukraine	Medical Center Salutem	Vinnytsia	Podolia Governorate
Ukraine	Medical Clinical Research Center of Medical Center LLC Health Clinic; Department of General Therapy	Vinnytsia	Podolia Governorate
Ukraine	LLC Medical Center INET 09	Zaporizhzhia	Katerynoslav Governorate
Ukraine	Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council	Zaporizhzhia	Katerynoslav Governorate
Ukraine	Zaporizhia City Multispecialty Clinical Hospital #9	Zaporizhzhye	Katerynoslav Governorate
Ukraine	Medical Centre of PE First Private Clinic	Zhytomir	Crimean Regional Governmenta
United Kingdom	University Hospital of Wales	Cardiff
United Kingdom	Queen Elizabeth University Hospital - PPDS	Glasgow
United Kingdom	Raigmore Hospital - PPDS; Highland Clinical Research Facility Center For Health Science	Inverness
United Kingdom	Walton Centre For Neurology and Neurosurgery	Liverpool
United Kingdom	The National Hospital for Neurology & Neurosurgery	London
United Kingdom	The Royal London Hospital	London
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 States	Dent Neurological Institute	Amherst	New York
United States	SFM Clinical Research, LLC	Boca Raton	Florida
United States	MS and Neuromuscular Center of Excellence	Clearwater	Florida
United States	Michigan Neurology Associates P.C.	Clinton Township	Michigan
United States	Columbus Neuroscience	Columbus	Ohio
United States	The Boster Center for MS	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Premier Neurology	Greenville	South Carolina
United States	Maxine Mesinger MS Clinic/Baylor College of Medicine; Neurology	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Center for Neurological Disorders	Milwaukee	Wisconsin
United States	Multiple Sclerosis Center of California	Newport Beach	California
United States	Meridian Clinical Research	Norfolk	Virginia
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Neurological Services of Orlando	Orlando	Florida
United States	SC3 Research Group, Inc	Pasadena	California
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	HonorHealth Neurology	Scottsdale	Arizona
United States	Vero Neurology	Vero Beach	Florida
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Colombia,  Croatia,  Egypt,  France,  Georgia,  Germany,  Hungary,  Ireland,  Italy,  Lebanon,  Mexico,  Morocco,  New Zealand,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  Spain,  Tunisia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Upper Limb Disability Progression Confirmed For at Least 12 Weeks	20% increase from baseline in Nine-Hole Peg Test (9-HPT) confirmed for at least 12 weeks.	Baseline up to approximately 5.5 years
Secondary	Time to Upper Limb Disability Progression Confirmed For at Least 24 Weeks	20% increases from baseline in 9-HPT confirmed for at least 24 weeks.	Baseline up to approximately 5.5 years
Secondary	Time to Disability Progression Confirmed For at Least 12 Weeks	Increase in EDSS Score is defined as an increase of >= 1.0 point from baseline 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.	Baseline up to approximately 5.5 years
Secondary	Time to Disability Progression Confirmed For at Least 24 Weeks	Increase in EDSS Score is defined as an increase of >= 1.0 point from baseline 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.	Baseline up to approximately 5.5 years
Secondary	Percent Change in Total Volume of T2 Lesions on MRI		Baseline up to week 120
Secondary	Percent Change in Total Brain Volume on MRI Scans		Week 24 to Week 120
Secondary	Percentage of Participants with Adverse Events		Baseline up to 8.5 years
Secondary	Percentage of Participants With Serious Adverse Events		Baseline up to 8.5 years
Secondary	Area Under the Serum Concentration-Time Curve (AUC) of Ocrelizumab		Baseline, Weeks 2, 12, 24, 48, 60, 72, and every 12 weeks till the end of the double-blind period and Weeks 0 and 48 of the OLE period
Secondary	Evaluation of Ocrelizumab Pharmacodynamics, as measured by B-Cell Levels in Blood		Baseline, Weeks 2, 24, 48, 72 and every 12 weeks till the end of the double-blind period and Weeks 0, 22, 46, 70 and 96 of the OLE period