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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04544436
Other study ID # BN42082
Secondary ID 2020-000893-69
Status Active, not recruiting
Phase Phase 3
First received
Last updated
Start date November 26, 2020
Est. completion date August 31, 2028

Study information

Verified date April 2024
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


Description:

Participants will be treated for a minimum of 120 weeks in the double-blind phase. Upon positive primary results after the double-blind phase, an optional higher dose extension treatment (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 low level 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 lower limit of normal.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 864
Est. completion date August 31, 2028
Est. primary completion date December 19, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years to 55 Years
Eligibility Inclusion Criteria: - Diagnosis of relapsing multiple sclerosis (RMS) (i.e., RRMS or aSPMS where participants still experience relapses) in accordance with the revised McDonald Criteria 2017 - At least two documented clinical relapses within the last 2 years prior to screening, or one clinical relapse in the year prior to screening. No relapse 30 days prior to screening and at baseline. - Participants must be neurologically stable for at least 30 days prior to randomization and baseline. - Expanded disability status scale (EDSS) score, at screening and baseline, from 0 to 5.5 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 at screening and over four trials at baseline respectively, up to 250 (inclusive) seconds - Documented MRI of brain with abnormalities consistent with MS at screening. - 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. - 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 Exclusion Criteria: - History of primary 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 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 within 24 weeks prior to screening or treatment with any experimental procedure for MS. - Previous use of anti-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. - 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 - Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab - 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 intravenous (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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ocrelizumab
The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (participants's body weight <75 kg) or 1800 mg (participant's body weight >/=75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion every 24 weeks. During the optional open-label extension (OLE) phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total).
Ocrelizumab
Ocrelizumab will be administered at a dose of 600 milligram (mg) every 24 weeks. The first dose of ocrelizumab will be administered as two 300 mg intravenous (IV) infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion every 24 weeks.
Antihistamine
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.
Methylprednisolone
Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Locations

Country Name City State
Argentina CEMIC Buenos Aires
Argentina Centro de Especialidades Neurológicas y Rehabilitación - CENyR Buenos Aires
Argentina Centro de Investigaciones Médicas Tucuman San Miguel de Tucuman
Australia Austin Hospital; Department of Neurology Heidelberg Victoria
Belgium Hospital Erasme Bruxelles
Belgium Revalidatie en MS Centrum Overpelt
Brazil Instituto de Neurologia de Curitiba Curitiba PR
Brazil Clinica Neurologica; Neurocirurgica de Joinville Joinville SC
Brazil IMV Pesquisa Neurológica Porto Alegre RS
Brazil CPQuali Pesquisa Clinica Ltda Sao Paulo SP
Canada Recherche Sepmus Inc. Greenfield Park Quebec
Canada Hotel-Dieu de Levis Quebec
Denmark Rigshospitalet Glostrup; Neurologisk Klinik Glostrup
France Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage Bordeaux
France CHU Hopital Gabriel Montpied; Service de Neurologie Clermont Ferrand
France CH St Vincent de Paul Lille
France Hôpital Charles Nicolle; Service de Neurologie Rouen
Germany Charite - Universitätsmedizin Berlin Berlin
Germany St. Josef-Hospital, Klinik für Neurologie Bochum
Germany Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften Dresden
Germany Universitätsklinikum Schleswig-Holstein; Klinik für Neurologie Kiel
Germany PANAKEIA - Arzneimittelforschung Leipzig GmbH Leipzig
Germany Universität Leipzig; Innere Medizin, Neurologie, Dermatologie Leipzig
Germany Universitätsklinikum Tübingen, Zentrum für Neurologie Tübingen
Germany Universitätsklinikum Ulm; Klinik für Neurologie Ulm
Germany Deutsche Klinik für Diagnostik; DKD Helios Klinik Wiesbaden, Abt. Neurologie Wiesbaden
Greece 401 Military Hospital of Athens; Neurology Department Athens
Greece AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept. Thessaloniki
Hungary S-Medicon Egeszsegugyi Szolgaltato Kft. Budapest
Hungary UNO Medical Trials Kft. Budapest
Hungary Somogy Vármegyei Kaposi Mór Oktató Kórház Kaposvar
Italy Universita? G. D'Annunzio; Dipartimento di Neuroscienze, Imaging e Scienze Cliniche Chieti Abruzzo
Italy Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari Milano Lombardia
Italy AOU Seconda Università degli Studi; Dip. Assistenziale Integrato Medicina Int-II Clinica Neurologica Napoli Campania
Italy AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica Napoli Campania
Italy IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla Pozzilli Molise
Italy NCL Institute Neuroscience Roma Lazio
Italy Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla Roma Lazio
Italy Policlinico Umberto I; Centro Sclerosi Multipla DAI Neuroscienze e Salute Mentale Roma Lazio
Peru Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion Bellavista
Peru Clinica Internacional; Unidad De Investigacion Lima
Peru Hospital Maria Auxiliadora Lima
Peru Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia Lima
Peru Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo; Peru Lima
Peru Clinica Sanchez Ferrer Trujillo
Poland Neurocentrum Bydgoszcz sp. z o.o Bydgoszcz
Poland COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny Gdansk
Poland MA-LEK Clinical Sp. Z o.o. Katowice
Poland Centrum Neurologii Krzysztof Selmaj Lodz
Poland SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM;Oddzial Kliniczny Neurologii Lodz
Poland Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak. Lublin
Poland Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych Plewiska
Poland EMC Instytut Medyczny SA Pozna?
Poland Nmedis sp. z o.o. Rzeszów
Poland Osrodek Badan Klinicznych Euromedis Szczecin
Poland Centrum Medyczne NeuroProtect Warszawa
Poland Instytut Psychiatrii i Neurologii II Klinika Neurologiczna Warszawa
Poland Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie Warszawa
Poland Wojskowy Instytut Medyczny - Pa?Stwowy Instytut Badawczy Warszawa
Portugal Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E) Braga
Portugal Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz; Neurologia Lisboa
Portugal Hospital de Santa Maria; Servico de Neurologia Lisboa
Russian Federation KSMU Interregional Clinical Diagnostic Centre Kazan Tatarstan
Russian Federation Vertebronevrologiya LLC Kazan Tatarstan
Russian Federation FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency Krasnoyarsk Krasnojarsk
Russian Federation Neiro Clinica LLC Moscow Moskovskaja Oblast
Russian Federation Research Center of Neurology of RAMS Moscow Moskovskaja Oblast
Russian Federation City Clinical Hospital #24; Multipal Sclerosis department Moskva Moskovskaja Oblast
Russian Federation Federal center of brain research and neurotechnologies Moskva Moskovskaja Oblast
Russian Federation National Center of Social Significant Disease Sankt-peterburg Leningrad
Russian Federation N.P. Bechtereva Institute of the Human Brain Sankt-petersburg Sankt Petersburg
Russian Federation Saratov State Medical University of RosZdrav; Neurology Saratov
Russian Federation City Hospital #40 of Kurortniy Administrative District St. Petersburg Sankt Petersburg
Russian Federation Nebbiolo Center for Clinical Trials Tomsk
Russian Federation Ulyanovsk Regional Clinical Hospital Ulyanovsk Uljanovsk
Russian Federation SHI Sverdlovsk Regional Clinical Hospital #1;Neurology Yekaterinburg Sverdlovsk
Spain Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia Barcelona
Spain Hospital Puerta del Mar; Sevicio de Neurologia Cadiz
Spain Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia Coruña LA Coruña
Spain Hospital Regional Universitario de Malaga ? Hospital General; Servicio de Neurologia Malaga
Spain Hospital Quiron de Madrid; Servicio de Neurologia Pozuelo de Alarcon Madrid
Spain Hospital Alvaro Cunqueiro; Servicio de Neurologia Vigo Pontevedra
Switzerland Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik Basel
Switzerland Inselspital Bern Medizin Neurologie; Neurologische Poliklinik Bern
Switzerland Ospedale Regionale di Lugano - Civico; Neurologia Lugano
Turkey Kocaeli University Hospital; Department of Neurology Kocaeli
Ukraine 5th Cherkasy City Center of Primary Health Care Cherkasy KIEV Governorate
Ukraine Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?; Neurology Department Chernihiv
Ukraine Bukovinsky SMU RMI Chernivtsi RCH Chernivtsi
Ukraine SI USSRI of Medical and Social Problems of Disabilities of MOHU Dnipro KIEV Governorate
Ukraine Regional Clinical Hospital; Neurology Department Ivano-Frankivsk
Ukraine Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital Kharkiv Kharkiv Governorate
Ukraine St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis Kharkov
Ukraine Medical Center Dopomoga Plus Kyiv Chernihiv Governorate
Ukraine Medical Center of Private Execution First Private Clinic Kyiv KIEV Governorate
Ukraine Lvivska oblasna tsentralna likarnia Lviv KIEV Governorate
Ukraine Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council Zaporizhzhia Katerynoslav Governorate
Ukraine Zaporizhia City Multispecialty Clinical Hospital #9 Zaporizhzhye Katerynoslav Governorate
United Kingdom Derriford Hospital Plymouth
United States Abington Neurological Associates Abington Pennsylvania
United States The NeuroMedical Clinic of Central Louisiana Alexandria Louisiana
United States Dent Neurological Institute Amherst New York
United States American Health Network Institute, LLC Avon Indiana
United States Mountain Neurological Research Center; Roaring Fork Neurologt, P.C. Basalt Colorado
United States Profound Research, LLC Carlsbad California
United States North Central Neurology Associates Cullman Alabama
United States UC Health Neurology Dayton Ohio
United States Henry Ford Health System Detroit Michigan
United States Advanced Neurology of Colorado, LLC Fort Collins Colorado
United States Alabama Neurology Associates Homewood Alabama
United States Tri-State Mountain Neurology Johnson City Tennessee
United States University of Kansas Medical Center Kansas City Kansas
United States Evergreen MS Center Kirkland Washington
United States Hope Neurology Knoxville Tennessee
United States Cleveland Clinic Lou Ruvo; Center for Brain Research Las Vegas Nevada
United States Bhupesh Dihenia M.D. P.A. Lubbock Texas
United States Neurology Associates, PA; Research Department Maitland Florida
United States Oklahoma Medical Research Foundation; MS Center of Excellence Oklahoma City Oklahoma
United States 21st Century Neurology Phoenix Arizona
United States Washington University School of Medicine Saint Louis Missouri
United States Neurology Center of San Antonio San Antonio Texas
United States Maine Medical Center Scarborough Maine
United States Stanford University Medical Center; Stanford Neuroscience Health Center Stanford California
United States University of South Florida Tampa Florida
United States Collaborative Neuroscience Network Inc. Torrance California
United States Dragonfly Research, LLC Wellesley Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Peru,  Poland,  Portugal,  Russian Federation,  Spain,  Switzerland,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Time to Onset of 12-week cCDP (cCDP12) Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT. Baseline up to approximately 4.3 years
Secondary Time to Onset of 24-week cCDP (cCDP24) Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT. Baseline up to approximately 4.3 years
Secondary Time to Onset of 48-week cCDP (cCDP48) Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT. Baseline up to approximately 4.3 years
Secondary Time to onset of cCDP12 independent of protocol-defined relapses (PDR) Time to onset of cCDP is defined as the first occurrence of a predefined confirmed progression event measured by EDSS, T25FWT or 9-HPT independent of protocol defined relapses. Baseline up to approximately 4.3 years
Secondary Time to onset of 12-week CDP (CDP12) CDP, defined as a sustained increase from baseline in EDSS score of >/=1.0 point in participants with a baseline EDSS score of Baseline up to approximately 4.3 years
Secondary Time to >/= 20% Increase in 12-week Confirmed by Timed 25-Foot Walk Test (T25FWT) The T25FWT is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant is directed to start at one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly and safely as possible. Baseline up to approximately 4.3 years
Secondary Annual rate of percent change from baseline in total brain volume Baseline up to approximately 4.3 years
Secondary Time to 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) The SDMT is a performance measure that has demonstrated sensitivity in detecting not only the presence of cognitive impairment but also changes in cognitive functioning over time and in response to treatment. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected orally. A four-point change from baseline is typically considered clinically meaningful. Baseline up to approximately 4.3 years
Secondary Time to 12-week confirmed 8-point increase in 12-Item Multiple Sclerosis Walking Scale (MSWS-12) Self-reported measure of the impact of MS on the individual's ability to walk Baseline up to approximately 4.3 years
Secondary Change in NfL at Week 48 for patients assigned to the higher dose ocrelizumab group Biomarker for neurodegneration NfL Baseline up to approximately 4.3 years
Secondary Change in NfL at Week 48 for patients assigned to the approved dose ocrelizumab group Biomarker for neurodegneration NfL Baseline up to approximately 4.3 years
Secondary Serum Concentration of Ocrelizumab at Specified Time points Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Secondary B-cell levels in blood Levels of blood B-cells is based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood Baseline up to approximately 4.3 years
Secondary Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood Levels of blood B-cells is based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood Baseline up to approximately 4.3 years
Secondary Proportion of Participants Achieving 5 or Less B-cells per Microliter of Blood in Participants with the High versus Low Affinity Fcgamma Receptor 3A (FcgR3A) Genotype per Arm Levels of blood B-cells is based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood Week 0, 2, 12, 24, 36, 48, 60, 72, 84, 96, 120
Secondary Change from Baseline in the Anti-Drug Antibody (ADA) Levels Week 0, 24, 48, 72, 96, 120
Secondary Levels of Neurofilament Light Chain (NfL) in Blood Biomarker for neurodegneration NfL Baseline up to approximately 4.3 years
Secondary Levels of Interleukin-6 (IL-6) in Blood Baseline up to approximately 4.3 years
Secondary Levels of Blood B-cells Levels of blood B-cells is based on a highly sensitive assay that can accurately measure below 5 B-cells per microliter in blood Baseline up to approximately 4.3 years
Secondary Levels of Lymphocytes in Blood Baseline up to approximately 4.3 years
Secondary Proportion of Participants with Different DNA Genotypes Week 0
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