AzTrials
AzTrials

Multiple Sclerosis, Primary ProgressivePhase 3O'HANDNCT04035005

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

A Phase 3 study testing Ocrelizumab in people with Multiple Sclerosis, Primary Progressive, run by Hoffmann-La Roche at 155 sites in 23 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Multiple Sclerosis, Primary Progressive
What is being tested?
Ocrelizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,013 participants
Where
155 sitesin 23 countries
Study dates
12 Aug 2019to 19 Jan 2028
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

155 sites in 23 countries.

155 sites in 23 countries

Ukraine21 sites

  • University hospital of Dnipro State Medical University

    Dnipro, 49089

  • LLC Medical Center Family Medicine Clinic

    Dnipro, 49600

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

    Kharkiv, 61022

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

    Kherson, Kherson Governorate, 73000

  • Treatment and Diagnostic Center of LLC MRT Elit

    Kropyvnytskyi, KIEV Governorate, 25005

  • Treatment and diagnostic Center Neuro Global of LLC Neuro Global

    Krykhivtsi, Ivano-Frankivsk Oblast, 76493

  • Medical Centre of PE First Private Clinic

    Kyiv, KIEV Governorate, 03037

  • Kyiv City Clinical Hospital #4

    Kyiv, KIEV Governorate, 03110

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

    Kyiv, KIEV Governorate, 04070

  • Medical Center Artes Medicum LLC

    Kyiv, Kyiv Oblast, 02002

  • Medical Center of LLC Medical Center Dopomoga Plus

    Kyiv, 02000

  • Private Enterprise Clinic Medicom

    Kyiv, 04219

  • Volyn Regional Clinical Hospital

    Lutsk, 43005

  • Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

    Lviv, Kharkiv Governorate, 79010

  • Communal noncommercial enterprise of Lviv Regional Council Lviv Regional Clinical Hospital

    Lviv, Lviv Oblast, 79010

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

    Uzhhorod, KIEV Governorate, 88018

  • Medical Center Salutem

    Vinnytsia, Podolia Governorate, 21009

  • LLC Medical Center Health Clinic

    Vinnytsia, Volhynian Governorate, 21009

  • LLC Medical Center Unimed

    Zaporizhzhya, Zaporizhzhia Oblast, 69000

  • LLC Medical Center INET 09

    Zaporizhzhya, 69035

  • Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council

    Zaporizhzhya, 69600

Other trials in Ukraine

Poland20 sites

  • Uniwersytecki Szpital Kliniczny w Bialymstoku Marii Sklodowskiej Curie 24a

    Bia?ystok, 15-276

  • Neurocentrum Bydgoszcz sp z o.o

    Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-796

  • Copernicus Podmiot Leczniczy Sp z o o

    Gda?sk, 80-803

  • Mazowieckie Centrum Badan Klinicznych

    Grodzisk Mazowiecki, 05-825

  • MA-LEK Clinical Sp. Z o.o.

    Katowice, 40-571

  • Novo-Med Zielinski i wsp SpJ

    Katowice, 40-584

  • NEURO-MEDIC Sp. z o. o.

    Katowice, 40-686

  • Specjalistyczna Praktyka Lekarska Dr n.med. Stanislaw Ochudlo

    Katowice, 40-752

  • RESMEDICA Spolka z o.o.

    Kielce, Świętokrzyskie Voivodeship, 25-726

  • Szpital Uniwersytecki w Krakowie

    Krakow, 31-503

  • Centrum Neurologii Krzysztof Selmaj

    Lodz, 90-324

  • Rejdak Konrad Indywidualna Praktyka Lekarska dr hab. Konrad Rejdak

    Lublin, Lublin Voivodeship, 20-410

  • Galen Clinic

    Lublin, 20-064

  • Wojewodzki Szpital Specjalistyczny

    Olsztyn, 10-561

  • Med-Polonia Sp. z o.o.

    Poznan, 60-693

  • SPZOZ Wojewodzki Szpital Specjalistyczny nr 3

    Rybnik, Silesian Voivodeship, 44-200

  • Centrum Medyczne Medyk

    Rzeszów, Podkarpackie Voivodeship, 35-055

  • EUROMEDIS Sp z o o

    Szczecin, 70-215

  • Centrum Medyczne NeuroProtect Zablocinska 10

    Warsaw, 01-684

  • Przychodnia EuroMediCare

    Wroclaw, Lower Silesian Voivodeship, 50-220

Other trials in Poland

Russia20 sites

  • Vertebronevrologiya LLC

    Kazan', Tatarstan Republic, 420043

  • Belyayev Clinical Hospital of the Kuzbass

    Kemerovo, 650066

  • Kirov State Medical Academy

    Kirov, 610027

  • Krasnoyarsk State Medical Academy

    Krasnoyarsk, Krasnoyarsk Krai, 660022

  • City Clinical Hospital a n Buyanov V M

    Moscow, Moscow Oblast, 115516

  • City Clinical Hospital #24

    Moscow, Moscow Oblast, 127015

  • Moscow Regional Research Clinical Institute Na Mfvladimirskiy

    Moscow, Moscow Oblast, 129110

  • Research Center of Neurology of RAMS

    Moskva, Moscow Oblast, 125367

  • Nizhegorodskaya Regional Clinical Hospital n.a. Semashko

    Nizhny Novgorod, Niznij Novgorod, 603126

  • MEDIS Limited Liability Company

    Nizhny Novgorod, Niznij Novgorod, 603137

  • SBHI of Nizhny Novgorod region City Clinical Hospital #3

    Nizhny Novgorod, Niznij Novgorod, 603155

  • FSBIH Siberian Regional Medical Centre of FMBA of Russia

    Novosibirsk, 630007

  • Perm Regional Clinical Hospital of Znak Pocheta Medal

    Perm, 614990

  • National Center of Socially Significant Diseases

    Saint Petersburg, Sankt-Peterburg, 197110

  • City Hospital #40 of Kurortniy Administrative District

    Saint Petersburg, Sankt-Peterburg, 197706

  • City Clinical Hospital #4

    Saransk, Saratov Oblast, 430032

  • Siberian State Medical University of Roszdrav

    Tomsk, 634050

  • Neftyanik Medical and Sanitary Unit

    Tumen, Moscow Oblast, 625000

  • Ulyanovsk Regional Clinical Hospital

    Ulyanovsk, Ulyanovsk Oblast, 432063

  • Sverdlovsk Regional Clinical Hospital 1

    Yekaterinburg, Sverdlovsk Oblast, 620102

Other trials in Russia

Spain10 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clinic de Barcelona

    Barcelona, 08036

  • Hospital Universitario Virgen de La Arrixaca

    El Palmar, Murcia, 30120

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario Puerta de Hierro - Majadahonda

    Madrid, 28222

  • Hospital Universitario Quironsalud Madrid

    Pozuelo de Alarcón, Madrid, 28223

  • Complejo Asistencial Universitario de Salamanca ? H. Clinico

    Salamanca, 37007

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital Universitari i Politecnic La Fe de Valencia

    Valencia, 46026

  • Complejo Hospitalario Universitario de Vigo

    Vigo, Pontevedra, 36312

Other trials in Spain

United Kingdom10 sites

  • University Hospital of Wales

    Cardiff, CF14 4XW

  • Queen Elizabeth University Hospital - PPDS

    Glasgow, G51 4TF

  • Raigmore Hospital - PPDS

    Inverness, IV2 3JH

  • The Royal London Hospital

    London, E1 1BB

  • The National Hospital for Neurology & Neurosurgery

    London, GT LON, WC1N 3BG

  • University of Nottingham

    Nottingham, NG7 2UH

  • Peninsula College of Medicine and Dentistry

    Plymouth, PL6 8BX

  • Salford Royal Hospital

    Salford, M6 8HD

  • Royal Hallamshire Hospital

    Sheffield, S10 2JF

  • Morriston Hospital

    Swansea, SA6 6NL

Other trials in United Kingdom

United States8 sites

  • MS and Neuromuscular Center of Excellence

    Clearwater, Florida, 33761

  • The Boster Center for Multiple Sclerosis a Singlepoint Healthcare Company

    Columbus, Ohio, 43235-5422

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • Neurological Services of Orlando

    Orlando, Florida, 32806

  • Albert Einstein Medical Center

    Philadelphia, Pennsylvania, 19141

  • Vero Neurology

    Vero Beach, Florida, 32960

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

  • Columbus Neuroscience

    Westerville, Ohio, 43082-6910

Other trials in United States

Italy8 sites

  • Fondazione Istituto G. Giglio di Cefalu

    Cefalù, Sicily, 90015

  • IRCCS AOM Azienda Ospedaliera Metropolitana

    Genoa, Liguria, 16132

  • Ospedale San Raffaele S.r.l. - PPDS

    Milan, Lombardy, 20132

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

    Naples, Campania, 80138

  • Azienda Ospedaliero-Universitaria San Luigi Gonzaga

    Orbassano, Piedmont, 10043

  • Fondazione Istituto Neurologico Mondino IRCCS

    Pavia, Lombardy, 27100

  • Fondazione PTV Policlinico Tor Vergata

    Rome, Lazio, 00133

  • Azienda Ospedaliera Sant'andrea

    Rome, Lazio, 00189

Other trials in Italy

Serbia7 sites

  • Military Medical Academy

    Belgrade, 11000

  • University Clinical Center of Serbia -PPDS

    Belgrade, 11000

  • Clinical Hospital Centre Zemun

    Belgrade, 11080

  • University Clinical Center Kragujevac

    Kragujevac, 34000

  • Clinical Center Nis

    Niš, 18000

  • Clinical Centre of Vojvodina

    Nova Sad, 21000

  • General Hospital Uzice

    Užice, 31000

Other trials in Serbia

France6 sites

  • CHU de Bordeaux - Hôpital Pellegrin

    Bordeaux, 33076

  • Centre Hospitalier Universitaire de Clermont Ferrand

    Clermont-Ferrand, 63003

  • CHRU Nancy

    Nancy, 54035

  • Hopital Guillaume Et Rene Laennec

    Nantes, 44805

  • CHU de Nimes - Hopital Universitaire Caremeau

    Nîmes, 30900

  • Hopital Civil

    Strasbourg, 67098

Other trials in France

Mexico5 sites

  • Hospital Angeles Chihuahua

    Chihuahua City, 31238

  • Neurociencias Estudios Clinicos S.C.

    Culiacán, Sinaloa, 80020

  • Grupo Medico Camino

    Mexico City, Mexico CITY (federal District), 03310

  • Unidad de Investigacion en Salud de Chihuahua

    Mexico City, 14050

  • Clinical Research Institute

    Tlalnepantla, 54055

Other trials in Mexico

Portugal5 sites

  • Hospital Garcia de Orta

    Almada, 2805-267

  • Hospital de Braga

    Braga, 4710-243

  • ULS de Loures-Odivelas, EPE - Hospital de Loures

    Loures, Lisbon District, 2674-514

  • Hospital de Santo Antonio

    Porto, 4099-001

  • Campus Neurologico Senior

    Torres Vedras, 2560-280

Other trials in Portugal

Canada4 sites

  • University of Alberta

    Edmonton, Alberta, T6G 2G3

  • Recherche Sepmus Inc.

    Greenfield Park, Quebec, J4V 2J2

  • Dalhousie Multiple Sclerosis Research Unit

    Halifax, Nova Scotia, B3H 4K4

  • St. Michael's Hospital

    Toronto, Ontario, M5B 1W8

Other trials in Canada

Romania4 sites

  • SC Clubul Sanatatii SRL

    Campulung Muscel, 115100

  • Cai Ferate Clinical Hospital

    Constanța, 900123

  • Spitalul Judetean de Urgenta Deva

    Deva, Hunedoara County, 330084

  • Targu Mures Clinical Emergency County Hospital

    Târgu Mure?, 540136

Other trials in Romania

Tunisia4 sites

  • Hopital Razi

    LA Mannouba, 2010

  • Fattouma Bourguiba University Hospital

    Monastir, 5000

  • Hospital Habib Bourguiba

    Sfax, 3029

  • Military Hospital of Tunis

    Tunis, 1008

Other trials in Tunisia

Australia3 sites

  • Brain and Mind Research Institute

    Camperdown, New South Wales, 2050

  • Austin Hospital

    Heidelberg, Victoria, 3084

  • Royal Melbourne Hospital

    Parkville, Victoria, 3050

Other trials in Australia

Belgium3 sites

  • Cliniques Universitaires St-Luc

    Brussels, 1200

  • UZ Antwerpen

    Edegem, Antwerpen, 2650

  • MS & Neurologisch Revalidatie Centrum

    Overpelt, 3900

Other trials in Belgium

Bulgaria3 sites

  • Military Medical Academy HBAT

    Pleven, 5800

  • Multiprofile Hospital For Active Treatment Avis Medica

    Pleven, 5800

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

    Sofia, 1113

Other trials in Bulgaria

Croatia3 sites

  • General Hospital Varazdin

    Varaždin, 42000

  • Clinical Hospital Sestre Milosrdnice

    Zagreb, 10000

  • University Hospital Center Zagreb

    Zagreb, 10000

Other trials in Croatia

Georgia3 sites

  • Pineo Medical Ecosystem LTD

    Tbilisi, 0114

  • The First University Clinic of Tbilisi State Medical University

    Tbilisi, 0141

  • Khechinashvili University Hospital

    Tbilisi, 179

Other trials in Georgia

Colombia2 sites

  • Clinica Colsanitas S.A. sede Clinica Universitaria Colombia

    Bogotá, 111321

  • Instituto Neurologico de Colombia INDEC

    Medellín, Antioquia, 50012

Other trials in Colombia

Lebanon2 sites

  • Hotel Dieu de France

    Achrafieh Beirut, 000000

  • Saint George University Medical Hospital

    El Achrafiyé, DUMMY_VALUE

Other trials in Lebanon

Morocco2 sites

  • CHU Mohammed VI

    Marrakesh, 40080

  • Centre Hospitalier Ibn Sina CHIS - Hopital des Specialites

    Rabat, 10100

Other trials in Morocco

New Zealand2 sites

  • New Zealand Clinical Research - Christchurch

    Christchurch, 8011

  • Dunedin Hospital

    Dunedin

Other trials in New Zealand

About this study

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

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).

Read the 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.

Being tested
Ocrelizumab, Placebo
Medical subject headings
Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OcrelizumabDrug

    Also called Ocrevus

    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.

  • PlaceboDrug

    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.

Study groups in NCT04035005
Study groupRoleWhat they receive
OcrelizumabExperimentalParticipants will receive ocrelizumab by intravenous (IV) infusion every 24 weeks.
Receives: Drug: Ocrelizumab
PlaceboPlacebo comparatorParticipants will receive placebo matched to ocrelizumab by IV infusion every 24 weeks.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) in FAS

    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.

    Measured: Up to approximately 243 weeks

  2. Time to Onset of cCDP12 in Magnetic Resonance Imaging (MRI) Activity Analysis Set

    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.

    Measured: Up to approximately 243 weeks

Secondary outcomes (13)

  1. Time to 12-week CDP in 9-HPT

    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.

    Measured: Up to approximately 243 weeks

  2. Time to 12-week CDP in EDSS

    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.

    Measured: Up to approximately 243 weeks

  3. Time to 24-week CDP in 9-HPT

    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.

    Measured: Up to approximately 243 weeks

  4. Time to 24-week CDP in EDSS

    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.

    Measured: Up to approximately 243 weeks

  5. Annual Rate of Change From Baseline in Radius of Total Volume of T2 Lesions

    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.

    Measured: Up to approximately 120 weeks

  6. Annual Rate of Percent Change From Week 24 in Total Brain Volume

    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.

    Measured: From Week 24 up to approximately 120 weeks

  7. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    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.

    Measured: From initiation of study drug up to approximately 10.5 years

  8. Serum Concentration of Ocrelizumab

    Measured: Up to approximately 10.5 years

  9. B-cell Levels in Blood

    Measured: Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228

  10. Change From Baseline in B-cell Levels

    Measured: Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228

  11. Percentage of Participants With B-cell Counts ≤5 Cells/μL

    Percentages have been rounded off.

    Measured: Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228

  12. Percentage of Participants With B-cell Counts ≤10 Cells/μL

    Percentages have been rounded off.

    Measured: Baseline, Weeks 2, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204 and 228

  13. Number of Participants With ADAs to Ocrelizumab

    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.

    Measured: Baseline up to approximately 10.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2019
  2. Study start12 Aug 2019
  3. Primary completion15 Jan 2025
  4. Study completion19 Jan 2028 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,013 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04035005
Sponsor's protocol ID
WA40404
Other IDs
2018-001511-73, 2023-505980-36-00, 2023, 2018
Acronym
O'HAND
Status last verified
Feb 2026
First submitted
17 Jul 2019
Last updated
23 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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

Publications

  • Giovannoni G, Airas L, Bove R, Cutter GR, Czarnecki M, Drulovic J, Hobart J, Kuhle J, Montalban X, Selmaj KW, Tur C, Wolinsky JS, Baldinotti A, Bonati U, Craveiro L, Giacobino C, Manfrini M, Schneble HM, Stevenson P, Wang Q, Yang K, Oh J; ORATORIO-HAND study group. Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis, including older patients and those with more advanced disease (ORATORIO-HAND): a multicentre, double-blind, randomised, placebo-controlled, phase 3b study. Lancet. 2026 May 30;407(10544):2195-2207. doi: 10.1016/S0140-6736(26)00617-3.

    PubMed 42208561

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ocrelizumab in people with Multiple Sclerosis, Primary Progressive, run by Hoffmann-La Roche at 155 sites in 23 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 23 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 155 sites in Ukraine, Poland, Russia, Spain, United Kingdom and 18 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) in FAS (time frame: Up to approximately 243 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04035005, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2026.

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