AzTrials
AzTrials

Multiple SclerosisPhase 3GAVOTTENCT04548999

A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)

A Phase 3 study testing Ocrelizumab, Antihistamine and Methylprednisolone in people with Multiple Sclerosis, run by Hoffmann-La Roche at 147 sites in 22 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 is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with PPMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Ocrelizumab, Antihistamine and Methylprednisolone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
769 participants
Where
147 sitesin 22 countries
Study dates
3 Dec 2020to 8 Sep 2027
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 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Diagnosis of PPMS
  • EDSS score at screening and baseline, from 3 to 6.5 inclusive
  • Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
  • Average 9HPT score over four trials (two trials with each hand) at screening and over four trials (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds
  • Score of ≥ to 2.0 on the Functional Systems (FS) scale for the pyramidal system that was due to lower extremity findings at screening and baseline
  • Documented magnetic resonance imaging (MRI) of brain with abnormalities consistent with MS
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  • Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization
  • Participants must be neurologically stable for at least 30 days prior to randomization and baseline
  • Disease duration from the onset of MS symptoms; if EDSS score at screening is ≤ 5, disease duration must be less than 10 years; If EDSS score at screening is > 5, disease duration must be less than 15 years
  • Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands
  • Females of childbearing potential: agreement to remain abstinent or use adequate contraceptive methods
  • Female participants, without reproductive potential may be enrolled e.g. if post-menopausal or if surgically sterile

Who cannot join

  • History of relapsing remitting or secondary progressive MS at screening
  • Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening
  • History of confirmed or suspected progressive multifocal leukoencephalopathy
  • History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
  • Immunocompromised state
  • Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
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  • Inability to complete an MRI or contraindication to gadolinium administration
  • Contraindications to mandatory pre-medications for infusion-related reaction (IRRs)
  • Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
  • Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
  • Significant, uncontrolled disease that may preclude participant from participating in the study
  • History of or currently active primary or secondary, non-drug-related, immunodeficiency
  • Pregnant or breastfeeding or intending to become pregnant
  • Lack of peripheral venous access
  • History of alcohol or other drug abuse within 12 months prior to screening
  • Treatment with any investigational agent or treatment with any experimental procedure for MS
  • Previous use of anti-cluster of differentiation 20 (CD20s) (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy
  • Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab
  • Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
  • Previous treatment with natalizumab within 4.5 months of baseline
  • Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
  • Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication
  • Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
  • Any previous history of transplantation or anti-rejection therapy
  • Treatment with IV immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization
  • Systemic corticosteroid therapy within 4 weeks prior to screening
  • Positive screening tests for active, latent, or inadequately treated hepatitis B
  • Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
  • Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above

Trial locations and contacts

147 sites in 22 countries.

147 sites in 22 countries

United States24 sites

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • Massachusetts General Hospital.

    Boston, Massachusetts, 02114

  • MS and Neuromuscular Center of Excellence

    Clearwater, Florida, 33761

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Neurology Clinic PC

    Cordova, Tennessee, 38018

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Michigan Institute for Neurological Disorders

    Farmington Hills, Michigan, 48334

  • Advanced Neurosciences Research LLC

    Fort Collins, Colorado, 80524

  • Northwell Health

    Great Neck, New York, 11021

  • Alabama Neurology Associates

    Homewood, Alabama, 35209

  • University of California Irvine

    Irvine, California, 92697

  • International Neurorehabilitation Institute

    Lutherville, Maryland, 21093

  • Wheaton Franciscan Healthcare - St. Francis Outpatient Center

    Milwaukee, Wisconsin, 53215

  • Advanced Neurosciences Institute

    Nashville, Tennessee, 37205

  • Jersey Shore University Medical Centre

    Neptune City, New Jersey, 07753

  • Lenox Hill Hospital

    New York, New York, 10075

  • Baptist Health Lexington

    Nicholasville, Kentucky, 40356

  • 21st Century Neurology

    Phoenix, Arizona, 85004

  • Lone Star Neurology of San Antonio

    San Antonio, Texas, 78258

  • Texas Institute for Neurological Disorders

    Sherman, Texas, 75092

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Stanford University Medical Center

    Stanford, California, 94305

  • University of South Florida

    Tampa, Florida, 33612

  • University of Massachusetts Medical School

    Worcester, Massachusetts, 01655

Other trials in United States

Russia15 sites

  • Vertebronevrologiya LLC

    Kazan', Tatarstan Republic, 420047

  • Center of Cardiology and Neurology

    Kirov, 610007

  • Regional clinical hospital named after prof. S.V. Ochapovsky

    Krasnodar, 350086

  • Krasnoyarsk State Medical Academy

    Krasnoyarsk, Krasnoyarsk Krai, 660022

  • FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency

    Krasnoyarsk, Krasnoyarsk Krai, 660037

  • Research Center of Neurology of RAMS

    Moscow, Moscow Oblast, 125367

  • Federal center of brain research and neurotechnologies

    Moskva, Moscow Oblast, 117997

  • City Clinical Hospital #24

    Moskva, Moscow Oblast, 127015

  • FSBIH Siberian Regional Medical Centre of FMBA of Russia

    Novosibirsk, 630007

  • Perm SMA n.a. academ. E.A. Vagner

    Perm, 614990

  • National Center of Social Significant Disease

    Saint Petersburg, Sankt-Peterburg, 197110

  • N.P. Bechtereva Institute of the Human Brain

    Saint Petersburg, Sankt-Peterburg, 197376

  • City Hospital #40 of Kurortniy Administrative District

    Saint Petersburg, Sankt-Peterburg, 197706

  • Ulyanovsk Regional Clinical Hospital

    Ulyanovsk, Ulyanovsk Oblast, 432063

  • SHI Sverdlovsk Regional Clinical Hospital #1

    Yekaterinburg, Sverdlovsk Oblast, 620102

Other trials in Russia

Poland14 sites

  • Neurocentrum Bydgoszcz sp. z o.o

    Bydgoszcz, 85-796

  • COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika

    Gdansk, 80-803

  • MA-LEK Clinical Sp. Z o.o.

    Katowice, 40-595

  • Szpital Specjalistyczny im. Rydygiera w Krakowie

    Krakow, 31-826

  • Centrum Neurologii Krzysztof Selmaj

    Lodz, 90-324

  • Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.

    Lublin, 20-410

  • Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.

    Oświęcim, 32-600

  • Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych

    Plewiska, 62-064

  • EMC Instytut Medyczny SA

    Późna, 60-309

  • Wojewódzki Szpital Specjalistyczny Nr 3

    Rybnik, 44-200

  • Nmedis sp. z o.o.

    Rzeszów, 35-323

  • Osrodek Badan Klinicznych Euromedis

    Szczecin, 70-215

  • Centrum Medyczne NeuroProtect

    Warsaw, 01-684

  • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna

    Warsaw, 02-957

Other trials in Poland

Turkey (Türkiye)12 sites

  • Gazi University Medical Faculty

    Ankara, 06500

  • Baskent Universitesi Ankara Hastanesi

    Çankaya, 06490

  • Cumhuriyet Universitesi Tip Fakultesi

    Center, 58060

  • Haseki Training and Research Hospital

    Istanbul, 34096

  • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi

    Istanbul, 34098

  • Sancaktepe Training and Research Hospital

    Istanbul, 34785

  • Selcuk University Medical Faculty

    Istanbul, 42131

  • Erciyes Universitesi

    Kayseri, 38039

  • Kocaeli University Hospital

    Kocaeli, 41380

  • Ege Üniversitesi Tip Fakültesi

    Lzmir, 35100

  • Mersin University Medical Faculty

    Mersin, 33079

  • Ondokuz Mayis University School of Medicine

    Samsun, 55139

Other trials in Turkey (Türkiye)

Brazil11 sites

  • L2 Ip Instituto de Pesquisas Clinicas Ltda ME

    Brasília, Federal District, 70200-730

  • Hospital das Clinicas - UNICAMP

    Campinas, São Paulo, 13083-888

  • Instituto de Neurologia de Curitiba

    Curitiba, Paraná, 81210-310

  • Hospital das Clinicas - UFG

    Goiânia, Goiás, 74605-020

  • Clinica Neurologica

    Joinville, Santa Catarina, 89201-165

  • Instituto Méderi de Pesquisa e Saúde

    Passo Fundo, Rio Grande do Sul, 99010-120

  • Hospital Moinhos de Vento

    Porto Alegre, Rio Grande do Sul, 90035-001

  • IMV Pesquisa Neurológica

    Porto Alegre, Rio Grande do Sul, 90110-000

  • Hospital Sao Lucas - PUCRS

    Porto Alegre, Rio Grande do Sul, 90610-000

  • Praxis Pesquisa Médica

    Santo André, São Paulo, 09090-790

  • CPQuali Pesquisa Clinica Ltda

    São Paulo, São Paulo, 01228-000

Other trials in Brazil

Ukraine11 sites

  • 5th Cherkasy City Center of Primary Health Care

    Cherkasy, 18029

  • SI USSRI of Medical and Social Problems of Disabilities of MOHU

    Dnipro, 49027

  • Regional Clinical Hospital

    Ivano-Frankivsk, 76008

  • St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU

    Kharkiv, 61068

  • State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine

    Kharkiv, 61068

  • Medical Center Dopomoga Plus

    Kyiv, 02123

  • Volyn Regional Clinical Hospital

    Lutsk, 43005

  • Lvivska oblasna tsentralna likarnia

    Lviv, 79010

  • Sumy Regional Clinical Hospital

    Sumy, 40031

  • Medical Clinical Research Center of Medical Center LLC Health Clinic

    Vinnytsi, 21009

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

    Zaporizhzhya, 69600

Other trials in Ukraine

Germany8 sites

  • Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften

    Dresden, 01307

  • Universitätsmedizin Greifswald

    Greifswald, 17475

  • Medizinische Hochschule Hannover, Klinik für Neurologie

    Hanover, 30625

  • Universität Leipzig

    Leipzig, 04103

  • Universitätsklinikum Münster

    Münster, 48149

  • Universitätsklinikum Tübingen, Zentrum für Neurologie

    Tübingen, 72076

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Deutsche Klinik für Diagnostik

    Wiesbaden, 65191

Other trials in Germany

France7 sites

  • CHU de Besancon Hopital Jean Minjoz

    Besançon, 25030

  • CHU Brest Hopital La Cavale Blanche

    Brest, 29609

  • Hopital Cote De Nacre

    Caen, 14033

  • CHU Hopital Gabriel Montpied

    Clermont-Ferrand, 63003

  • CH St Vincent de Paul

    Lille, 59000

  • Hopital Central - CHU de Nancy

    Nancy, 54035

  • Hopital Hautepierre - CHU Strasbourg

    Strasbourg, 67098

Other trials in France

Italy7 sites

  • Ospedale S.Antonio Abate

    Gallarate, Lombardy, 21013

  • IRCCS Ospedale San Raffaele

    Milan, Lombardy, 20132

  • A. O. U. Federico II

    Naples, Campania, 80131

  • AOU Seconda Università degli Studi

    Naples, Campania, 80138

  • IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla

    Pavia, Lombardy, 27100

  • Azienda Ospedaliera Sant'Andrea

    Rome, Lazio, 00189

  • AOU Città della Salute e della Scienza

    Turin, Piedmont, 10126

Other trials in Italy

Hungary5 sites

  • Semmelweis Egyetem Idegsebeszeti és Neurointervencios Klinika

    Budapest, 1145

  • UNO Medical Trials Kft.

    Budapest, 1152

  • Petz Aladar Megyei Oktato Korhaz

    Győr, 9024

  • Somogy Megyei Kaposi Mor Oktato Korhaz

    Kaposvár, 7400

  • Kistarcsai Flor Ferenc Korhaz

    Kistarcsa, 2143

Other trials in Hungary

Mexico4 sites

  • Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.

    Guadalajara, Jalisco, 44130

  • Grupo Médico Camino S.C.

    México, 03600

  • Clinstile S.A de C.V.

    Mexico City, Mexico CITY (federal District), 06700

  • Neurociencias Prisma, A.C

    San Luis Potosí City, San Luis Potosí, 78216

Other trials in Mexico

Portugal4 sites

  • Hospital de Braga

    Braga, 4710-243

  • Hospital Santo Antonio dos Capuchos

    Lisbon, 1169-050

  • Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz

    Lisbon, 1349-019

  • Hospital Geral de Santo Antonio

    Porto, 4099-001

Other trials in Portugal

Spain4 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Universitario Puerta De Hierro Majadahonda

    Madrid, 28222

  • Hospital Universitario Virgen de Arrixaca

    Murcia

  • Hospital Quiron de Madrid

    Pozuelo de Alarcón, Madrid, 28223

Other trials in Spain

United Kingdom4 sites

  • Charing Cross Hospital

    London, W6 8RF

  • National Hospital for Neurology and Neurosurgery,

    London, WC1 3BG

  • Royal Victoria Infirmary

    Newcastle upon Tyne, NE1 4LP

  • Derriford Hospital

    Plymouth, PL6 8DH

Other trials in United Kingdom

Argentina3 sites

  • CEMIC Saavedra

    Buenos Aires, 1431

  • Centro de Especialidades Neurológicas y Rehabilitación - CENyR

    Buenos Aires, C1424

  • INECO

    Rosario, S2000QGB

Other trials in Argentina

Canada3 sites

  • Centre de Recherche Saint-Louis

    Lévis, Quebec, G6W 0M5

  • Chum Campus Notre Dame

    Montreal, Quebec, H2X 0A9

  • MUCH - Montreal Neurological Institute & Hospital

    Montreal, Quebec, H3A 2B4

Other trials in Canada

Peru3 sites

  • Hospital Nacional Guillermo Almenara Irigoyen

    La Victoria, Lima, Lima 13

  • Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo

    Lima, Lima 01

  • Hospital Nacional Dos de Mayo

    Lima

Other trials in Peru

Bulgaria2 sites

  • UMHAT Dr. Georgi Stranski

    Pleven, 5800

  • MHATNP Sveti Naum EAD

    Sofia, 1113

Other trials in Bulgaria

Denmark2 sites

  • Aalborg Universitetshospital

    Aalborg, 9000

  • Rigshospitalet Glostrup

    Glostrup Municipality, 2600

Other trials in Denmark

Greece2 sites

  • Hospital Eginition

    Athens, 115 28

  • 401 Military Hospital of Athens

    Athens, 11525

Other trials in Greece

Belgium1 site

  • Revalidatie en MS Centrum

    Overpelt, 3900

Other trials in Belgium

Switzerland1 site

  • Inselspital Bern Medizin Neurologie

    Bern, 3010

Other trials in Switzerland

About this study

Official title: A Phase IIIB Multicenter, Randomized, Double-blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis

This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and PK of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks (Q24W) in participants with PPMS, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.

Read the detailed description

Participants will be treated for a minimum of 120 weeks in the double-blind treatment (DBT) phase. Upon positive primary results after the DBT phase, an optional higher dose extension treatment, open-label extension (OLE) phase is planned for eligible participants. The OLE will be carried out for approximately 96 weeks. Participants will be followed for safety for 48 weeks thereafter. Participants whose B-cell levels still did not replete to their baseline level or the lower limit of normal (LLN), whichever is lower, will move into the B-cell monitoring (BCM) phase following the safety follow-up phase. The study will end when all participants who were not treated with an alternative B-cell depleting therapy have repleted their B-cells to the baseline value or the LLN.

Being tested
Ocrelizumab, Antihistamine, Methylprednisolone
Keywords
Primary Progressive Multiple Sclerosis; Higher Dose of CD20 Antibody Ocrelizumab; Efficacy, Safety and Pharmacokinetics
Medical subject headings
Multiple Sclerosis, 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 actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight <75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W.

    During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total)

  • OcrelizumabDrug

    Also called Ocrevus

    Ocrelizumab will be administered at a dose of 600 mg Q24W. 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 IV infusion Q24W.

  • AntihistamineDrug

    Also called Non-Investigational Medicinal Product

    Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

  • MethylprednisoloneDrug

    Also called Non-Investigational Medicinal Product

    Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Study groups in NCT04548999
Study groupRoleWhat they receive
Ocrelizumab Higher DoseExperimentalParticipants will be randomized to receive a minimum of 5 higher treatment doses based on their body weight at baseline: 1200 mg (participant's body weight <75 kilograms [kg]) or 1800 mg (participant's body weight ≥ 75 kg) of ocrelizumab administered by IV infusion Q24W in the DBT phase. During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.
Receives: Drug: Ocrelizumab; Drug: Antihistamine; Drug: Methylprednisolone
Ocrelizumab Approved DoseActive comparatorParticipants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by IV infusion Q24W in the DBT phase. During the optional OLE phase, participants will be offered a higher dose of ocrelizumab (either 1200 or 1800 mg), based on their body weight at OLE baseline, for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.
Receives: Drug: Ocrelizumab; Drug: Antihistamine; Drug: Methylprednisolone

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)

    Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of the 3 criteria: 1) CDP=12-week confirmed increase (CI) from baseline (FB) in expanded disability status scale (EDSS) score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 12-week CI of ≥20% FB in Timed 25-foot Walk Test (T25FWT) score OR 3)12-week CI of ≥ 20% FB in 9-hole Peg Test (9-HPT) score. EDSS = disability scale that ranges in 0.5-point steps from 0 [normal]-10.0 [death]. In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.

    Measured: Up to approximately 4.5 years

Secondary outcomes (18)

  1. Time to Onset of 24-week cCDP (cCDP24)

    Time to onset of a 24 week cCDP=first occurrence of a 24-week cCDP according to at least 1 of 3 criteria: 1) CDP=24-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 24-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 24-week CI of ≥20% FB in T25FWT score OR 3) 24-week CI of ≥ 20% FB in 9-HPT score. EDSS = disability scale that ranges in 0.5-point steps from 0 [normal]-10.0 [death]. In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.

    Measured: Up to approximately 4.5 years

  2. Time to Onset of cCDP12 Independent of Protocol-defined Relapses (PDR) or Progression Independent of Relapse Activity (PIRA)

    Time to onset of 12-week cCDP=first occurrence of a 12-week cCDP according to at least 1 of 3 criteria: 1) CDP=12-week CI from baseline in EDSS score of ≥1.0 point in participants with baseline EDSS score of ≤5.5 or 12-week CI≥0.5 point in participants with baseline EDSS score of >5.5 OR 2) 12-week CI of ≥20% FB in T25FWT score OR 3) 12-week CI of ≥ 20% FB in 9-HPT score. EDSS score, T25FWT \& 9-HPT are the same as defined in primary outcome measure. Protocol-defined relapse=occurrence of new or worsening neurological symptoms attributable to MS and immediately preceded by a relatively stable or improving neurological state of at least 30 days. Symptoms persist for at least 24 hours \& accompanied by objective neurological worsening consistent with an increase of one of the following: Half a step (0.5 point) on the EDSS; Two points on one of the functional system scores (FSS) (pyramidal, ambulation, cerebellar, brainstem, sensory, or visual); One point on ≥2 more of the FSS.

    Measured: Up to approximately 4.5 years

  3. Time to Onset of 12-week Confirmed Disability Progression (CDP12)

    CDP was defined as a 12-week confirmed increase from baseline in EDSS score of ≥1.0 point in participants with a baseline EDSS score of ≤5.5 or a 12-week CI ≥0.5 points in participants with a baseline EDSS score of >5.5. The 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 and bladder, and 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 range 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 4.5 years

  4. Time to ≥ 20% Increase in 12-week Confirmed T25FWT

    T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. A 20% change from baseline of the averaged T25FWT was considered clinically meaningful.

    Measured: Up to approximately 4.5 years

  5. Time to Onset of 12-week Confirmed ≥ 4-point Worsening in Symbol Digit Modalities Test (SDMT)

    The SDMT is a performance measure that demonstrated sensitivity in detecting the presence of cognitive impairment and changes in cognitive functioning over time \& in response to treatment. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants were asked to pair specific numbers with given geometric figures within 90 seconds. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement. A four-point change from baseline was considered clinically meaningful.

    Measured: Up to approximately 4.5 years

  6. Time to Onset of 24-week Confirmed ≥ 8-point Increase in 12-Item Multiple Sclerosis Walking Scale (MSWS-12)

    The MSWS-12 was a 12-item self-report measure of the impact of MS on the participant's ability to walk during the past 2 weeks. Each item was scored on a 5-point Likert scale ranging from 1 (not at all) to 5 (extremely likely). Scores were summed and linearly converted to a 0-100 scale with higher scores indicating greater impact of MS on walking ability. An 8-point change was considered clinically meaningful.

    Measured: Up to approximately 4.5 years

  7. Annual Rate of Percent Change From Baseline in Total Brain Volume

    Brain volume was measured using magnetic resonance imaging (MRI) scans. Mean difference in annual rate of percent change from baseline in total brain volume between the higher and approved dose of ocrelizumab arms in participants with RMS where no treatment discontinuation nor initiation of alternative MS treatment occurred, are reported.

    Measured: Up to approximately 4.5 years

  8. Annual Rate of Percent Change From Baseline in Thalamic Volume

    Thalamic volume was measured using MRI scans. Mean difference in annual rate of percent change from baseline in thalamic volume between the higher and approved dose of ocrelizumab arms in participants with RMS where no treatment discontinuation nor initiation of alternative MS treatment occurred, are reported.

    Measured: Up to approximately 4.5 years

  9. Ratio of Fold Change From Baseline in Neurofilament Light Chain (NfL) Levels at Week 96

    NfL is a biomarker of neuroinflammation in CSF. Ratio of the mean change from baseline in NfL at Week 96 between the higher and approved dose of ocrelizumab arms in PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric means at Week 96 vs baseline).

    Measured: At Week 96

  10. Fold Change From Baseline in NfL Levels at Week 96 Within the Higher Dose Ocrelizumab Group

    NfL is a biomarker of neuroinflammation in CSF. Mean change from baseline in NfL at Week 96 for PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab higher dose group have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric mean at Week 96 vs baseline).

    Measured: At Week 96

  11. Fold Change From Baseline in NfL Levels at Week 96 Within the Approved Dose Ocrelizumab Group

    NfL is a biomarker of neuroinflammation in CSF. Mean change from baseline in NfL at Week 96 for PPMS participants where no treatment discontinuation nor initiation of alternative MS treatment occurred within the ocrelizumab 600 mg group have been reported. The results correspond to fold change from baseline (i.e., ratio of adjusted geometric mean at Week 96 vs baseline).

    Measured: At Week 96

  12. Number of Participants With Adverse Events (AEs)

    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.

    Measured: From initiation of study drug up to approximately 6.8 years

  13. Area Under the Serum Concentration-time Curve (AUC) of Ocrelizumab Over the First Dosing Interval

    Measured: Day 1 to Week 24

  14. B-cell Levels in Blood

    Measured: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

  15. Percent Change From Baseline in B-cell Levels

    Measured: Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

  16. Percentage of Participants Who Achieved ≤ 5 B-cells/μL of Blood

    Measured: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

  17. Percentage of Participants Who Achieved ≤ 0.4 B-cells/μL of Blood

    Measured: Baseline, Weeks 2, 24, 48, 72, 96, 120, 144, 168, 192 and 216

  18. Percentage of Participants With Anti-drug Antibodies (ADAs) to Ocrelizumab

    Participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer unit (t.u.) greater than the baseline titer result. Percentages have been rounded off.

    Measured: Up to approximately 4.5 years

Timeline

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

  1. First posted16 Sep 2020
  2. Study start3 Dec 2020
  3. Primary completion30 Jun 2025
  4. Study completion8 Sep 2027 (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
769 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04548999
Sponsor's protocol ID
BN42083
Other IDs
2020-000894-26, 2023-506515-18-00, 2023
Acronym
GAVOTTE
Status last verified
Jun 2026
First submitted
9 Sep 2020
Last updated
24 Jul 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

  • Hauser SL, Giovannoni G, Montalban X, Oh J, Bar-Or A, Sormani MP, Weber MS, Stoll S, Nicholas JA, Nehrych T, Bonek R, Selmaj K, Maciejowski M, Zecevic D, Raposo C, Owen R, Bonati U, Madjar K, Harfst E, Wang Q, Raievska A, Manfrini M, Schneble HM, Kappos L; MUSETTE and GAVOTTE Study Groups. Efficacy and safety of a bodyweight-adjusted higher dose of ocrelizumab in relapsing (MUSETTE) and primary progressive (GAVOTTE) multiple sclerosis: two multicentre, randomised, double-blind, parallel-group phase 3b trials. Lancet. 2026 May 30;407(10544):2180-2194. doi: 10.1016/S0140-6736(26)00147-9.

    PubMed 42208560

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ocrelizumab, Antihistamine and Methylprednisolone in people with Multiple Sclerosis, run by Hoffmann-La Roche at 147 sites in 22 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 12 inclusion and 29 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 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 147 sites in United States, Russia, Poland, Turkey (Türkiye), Brazil and 17 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. 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 24 Jul 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) (time frame: Up to approximately 4.5 years). 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 NCT04548999, 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 24 Jul 2026.

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