A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)
GAVOTTE
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
3 other identifiers
interventional
769
22 countries
149
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3 multiple-sclerosis
Started Dec 2020
Longer than P75 for phase_3 multiple-sclerosis
149 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 9, 2020
CompletedFirst Posted
Study publicly available on registry
September 16, 2020
CompletedStudy Start
First participant enrolled
December 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 8, 2027
ExpectedMarch 30, 2026
March 1, 2026
4.6 years
September 9, 2020
March 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Time to Onset of Composite Confirmed Disability Progression (cCDP) Sustained for at least 12 Weeks
Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by Expanded Disability Status Scale (EDSS), Timed 25-foot Walk Test (T25FWT) or 9-hole Peg Test (9-HPT)
Baseline up to approximately 4.3 years
Secondary Outcomes (16)
Time to Onset of 12-week Composite Confirmed Disability Progression (cCDP12) Independent of Protocol-defined Relapses (PDR)
Baseline up to approximately 4.3 years
Time to Onset of 12-week Confirmed Disability Progression (CDP12)
Baseline up to approximately 4.3 years
Time to ≥ 20% Increase in 12-week Confirmed by T25FWT
Baseline up to approximately 4.3 years
Change in Neurofilament Light (NfL) at Week 96
Baseline up to Week 96
Time to 12-week Confirmed 8-point Increase in 12-item Multiple Sclerosis Walking Scale (MSWS12)
Baseline up to approximately 4.3 years
- +11 more secondary outcomes
Study Arms (2)
Ocrelizumab Higher Dose
EXPERIMENTALParticipants 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.
Ocrelizumab Approved Dose
ACTIVE 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.
Interventions
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)
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.
Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.
Eligibility Criteria
You may qualify if:
- 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
- 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
You may not qualify if:
- 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
- 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
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (149)
Alabama Neurology Associates
Homewood, Alabama, 35209, United States
21st Century Neurology
Phoenix, Arizona, 85004, United States
University of California Irvine
Irvine, California, 92697, United States
Stanford University Medical Center
Stanford, California, 94305, United States
University of Colorado Denver
Aurora, Colorado, 80045, United States
Advanced Neurosciences Research LLC
Fort Collins, Colorado, 80524, United States
MS and Neuromuscular Center of Excellence
Clearwater, Florida, 33761, United States
University of South Florida
Tampa, Florida, 33612, United States
Baptist Health Lexington
Nicholasville, Kentucky, 40356, United States
International Neurorehabilitation Institute
Lutherville, Maryland, 21093, United States
Massachusetts General Hospital.
Boston, Massachusetts, 02114, United States
University of Massachusetts Medical School
Worcester, Massachusetts, 01655, United States
Michigan Institute for Neurological Disorders
Farmington Hills, Michigan, 48334, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Jersey Shore University Medical Centre
Neptune City, New Jersey, 07753, United States
Northwell Health
Great Neck, New York, 11021, United States
Lenox Hill Hospital
New York, New York, 10075, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Neurology Clinic PC
Cordova, Tennessee, 38018, United States
Advanced Neurosciences Institute
Nashville, Tennessee, 37205, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Lone Star Neurology of San Antonio
San Antonio, Texas, 78258, United States
Texas Institute for Neurological Disorders
Sherman, Texas, 75092, United States
Wheaton Franciscan Healthcare - St. Francis Outpatient Center
Milwaukee, Wisconsin, 53215, United States
CEMIC Saavedra
Buenos Aires, 1431, Argentina
Centro de Especialidades Neurológicas y Rehabilitación - CENyR
Buenos Aires, C1424, Argentina
INECO
Rosario, S2000QGB, Argentina
Revalidatie en MS Centrum
Overpelt, 3900, Belgium
L2 Ip Instituto de Pesquisas Clinicas Ltda ME
Brasília, Federal District, 70200-730, Brazil
Hospital das Clinicas - UFG
Goiânia, Goiás, 74605-020, Brazil
Instituto de Neurologia de Curitiba
Curitiba, Paraná, 81210-310, Brazil
Instituto Méderi de Pesquisa e Saúde
Passo Fundo, Rio Grande do Sul, 99010-120, Brazil
Hospital Moinhos de Vento
Porto Alegre, Rio Grande do Sul, 90035-001, Brazil
IMV Pesquisa Neurológica
Porto Alegre, Rio Grande do Sul, 90110-000, Brazil
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000, Brazil
Clinica Neurologica
Joinville, Santa Catarina, 89201-165, Brazil
Hospital das Clinicas - UNICAMP
Campinas, São Paulo, 13083-888, Brazil
Praxis Pesquisa Médica
Santo André, São Paulo, 09090-790, Brazil
CPQuali Pesquisa Clinica Ltda
São Paulo, São Paulo, 01228-000, Brazil
UMHAT Dr. Georgi Stranski
Pleven, 5800, Bulgaria
MHATNP Sveti Naum EAD
Sofia, 1113, Bulgaria
Centre de Recherche Saint-Louis
Lévis, Quebec, G6W 0M5, Canada
Chum Campus Notre Dame
Montreal, Quebec, H2X 0A9, Canada
MUCH - Montreal Neurological Institute & Hospital
Montreal, Quebec, H3A 2B4, Canada
Aalborg Universitetshospital
Aalborg, 9000, Denmark
Rigshospitalet Glostrup
Glostrup Municipality, 2600, Denmark
CHU de Besancon Hopital Jean Minjoz
Besançon, 25030, France
CHU Brest Hopital La Cavale Blanche
Brest, 29609, France
Hopital Cote De Nacre
Caen, 14033, France
CHU Hopital Gabriel Montpied
Clermont-Ferrand, 63003, France
CH St Vincent de Paul
Lille, 59000, France
Hopital Central - CHU de Nancy
Nancy, 54035, France
Hopital Hautepierre - CHU Strasbourg
Strasbourg, 67098, France
Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
Dresden, 01307, Germany
Universitätsmedizin Greifswald
Greifswald, 17475, Germany
Medizinische Hochschule Hannover, Klinik für Neurologie
Hanover, 30625, Germany
Universität Leipzig
Leipzig, 04103, Germany
Universitätsklinikum Münster
Münster, 48149, Germany
Universitätsklinikum Tübingen, Zentrum für Neurologie
Tübingen, 72076, Germany
Universitätsklinikum Ulm
Ulm, 89081, Germany
Deutsche Klinik für Diagnostik
Wiesbaden, 65191, Germany
Hospital Eginition
Athens, 115 28, Greece
401 Military Hospital of Athens
Athens, 11525, Greece
Semmelweis Egyetem Idegsebeszeti és Neurointervencios Klinika
Budapest, 1145, Hungary
UNO Medical Trials Kft.
Budapest, 1152, Hungary
Petz Aladar Megyei Oktato Korhaz
Győr, 9024, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvár, 7400, Hungary
Kistarcsai Flor Ferenc Korhaz
Kistarcsa, 2143, Hungary
A. O. U. Federico II
Naples, Campania, 80131, Italy
AOU Seconda Università degli Studi
Naples, Campania, 80138, Italy
Azienda Ospedaliera Sant'Andrea
Rome, Lazio, 00189, Italy
Ospedale S.Antonio Abate
Gallarate, Lombardy, 21013, Italy
IRCCS Ospedale San Raffaele
Milan, Lombardy, 20132, Italy
IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
Pavia, Lombardy, 27100, Italy
AOU Città della Salute e della Scienza
Turin, Piedmont, 10126, Italy
Centro de Investigacion Medico Biologico y Terapia Avanzada, S.C.
Guadalajara, Jalisco, 44130, Mexico
Clinstile S.A de C.V.
Mexico City, Mexico CITY (federal District), 06700, Mexico
Neurociencias Prisma, A.C
San Luis Potosí City, San Luis Potosí, 78216, Mexico
Grupo Médico Camino S.C.
México, 03600, Mexico
Hospital Nacional Guillermo Almenara Irigoyen
La Victoria, Lima, Lima 13, Peru
Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo
Lima, Lima 01, Peru
Hospital Nacional Dos de Mayo
Lima, Peru
Neurocentrum Bydgoszcz sp. z o.o
Bydgoszcz, 85-796, Poland
COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika
Gdansk, 80-803, Poland
MA-LEK Clinical Sp. Z o.o.
Katowice, 40-595, Poland
Szpital Specjalistyczny im. Rydygiera w Krakowie
Krakow, 31-826, Poland
Centrum Neurologii Krzysztof Selmaj
Lodz, 90-324, Poland
Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
Lublin, 20-410, Poland
Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.
Oświęcim, 32-600, Poland
Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
Plewiska, 62-064, Poland
EMC Instytut Medyczny SA
Późna, 60-309, Poland
Wojewódzki Szpital Specjalistyczny Nr 3
Rybnik, 44-200, Poland
Nmedis sp. z o.o.
Rzeszów, 35-323, Poland
Osrodek Badan Klinicznych Euromedis
Szczecin, 70-215, Poland
Centrum Medyczne NeuroProtect
Warsaw, 01-684, Poland
Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
Warsaw, 02-957, Poland
Hospital de Braga
Braga, 4710-243, Portugal
Hospital Santo Antonio dos Capuchos
Lisbon, 1169-050, Portugal
Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz
Lisbon, 1349-019, Portugal
Hospital Geral de Santo Antonio
Porto, 4099-001, Portugal
Krasnoyarsk State Medical Academy
Krasnoyarsk, Krasnoyarsk Krai, 660022, Russia
FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
Krasnoyarsk, Krasnoyarsk Krai, 660037, Russia
Research Center of Neurology of RAMS
Moscow, Moscow Oblast, 125367, Russia
Federal center of brain research and neurotechnologies
Moskva, Moscow Oblast, 117997, Russia
City Clinical Hospital #24
Moskva, Moscow Oblast, 127015, Russia
Leningrad Regional Clinical Hospital
Saint Petersburg, Sankt-Peterburg, 194291, Russia
National Center of Social Significant Disease
Saint Petersburg, Sankt-Peterburg, 197110, Russia
N.P. Bechtereva Institute of the Human Brain
Saint Petersburg, Sankt-Peterburg, 197376, Russia
City Hospital #40 of Kurortniy Administrative District
Saint Petersburg, Sankt-Peterburg, 197706, Russia
SHI Sverdlovsk Regional Clinical Hospital #1
Yekaterinburg, Sverdlovsk Oblast, 620102, Russia
Vertebronevrologiya LLC
Kazan', Tatarstan Republic, 420047, Russia
Ulyanovsk Regional Clinical Hospital
Ulyanovsk, Ulyanovsk Oblast, 432063, Russia
Center of Cardiology and Neurology
Kirov, 610007, Russia
Regional clinical hospital named after prof. S.V. Ochapovsky
Krasnodar, 350086, Russia
FSBIH Siberian Regional Medical Centre of FMBA of Russia
Novosibirsk, 630007, Russia
Perm SMA n.a. academ. E.A. Vagner
Perm, 614990, Russia
Hospital Quiron de Madrid
Pozuelo de Alarcón, Madrid, 28223, Spain
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitario Puerta De Hierro Majadahonda
Madrid, 28222, Spain
Hospital Universitario Virgen de Arrixaca
Murcia, Spain
Inselspital Bern Medizin Neurologie
Bern, 3010, Switzerland
Gazi University Medical Faculty
Ankara, 06500, Turkey (Türkiye)
Cumhuriyet Universitesi Tip Fakultesi
Center, 58060, Turkey (Türkiye)
Baskent Universitesi Ankara Hastanesi
Çankaya, 06490, Turkey (Türkiye)
Haseki Training and Research Hospital
Istanbul, 34096, Turkey (Türkiye)
Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi
Istanbul, 34098, Turkey (Türkiye)
Sancaktepe Training and Research Hospital
Istanbul, 34785, Turkey (Türkiye)
Selcuk University Medical Faculty
Istanbul, 42131, Turkey (Türkiye)
Erciyes Universitesi
Kayseri, 38039, Turkey (Türkiye)
Kocaeli University Hospital
Kocaeli, 41380, Turkey (Türkiye)
Ege Üniversitesi Tip Fakültesi
Lzmir, 35100, Turkey (Türkiye)
Mersin University Medical Faculty
Mersin, 33079, Turkey (Türkiye)
Ondokuz Mayis University School of Medicine
Samsun, 55139, Turkey (Türkiye)
5th Cherkasy City Center of Primary Health Care
Cherkasy, 18029, Ukraine
SI USSRI of Medical and Social Problems of Disabilities of MOHU
Dnipro, 49027, Ukraine
Regional Clinical Hospital
Ivano-Frankivsk, 76008, Ukraine
St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU
Kharkiv, 61068, Ukraine
State Institution Institute of Neurology, Psychiatry and Narcology of NAMS of Ukraine
Kharkiv, 61068, Ukraine
Medical Center Dopomoga Plus
Kyiv, 02123, Ukraine
Medical Center of Private Execution First Private Clinic
Kyiv, 03037, Ukraine
Volyn Regional Clinical Hospital
Lutsk, 43005, Ukraine
Lvivska oblasna tsentralna likarnia
Lviv, 79010, Ukraine
Sumy Regional Clinical Hospital
Sumy, 40031, Ukraine
Medical Clinical Research Center of Medical Center LLC Health Clinic
Vinnytsi, 21009, Ukraine
Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
Zaporizhzhia, 69600, Ukraine
Charing Cross Hospital
London, W6 8RF, United Kingdom
National Hospital for Neurology and Neurosurgery,
London, WC1 3BG, United Kingdom
Royal Victoria Infirmary
Newcastle upon Tyne, NE1 4LP, United Kingdom
Derriford Hospital
Plymouth, PL6 8DH, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 9, 2020
First Posted
September 16, 2020
Study Start
December 3, 2020
Primary Completion
June 30, 2025
Study Completion (Estimated)
September 8, 2027
Last Updated
March 30, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
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