A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS)
Multiple Sclerosis
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
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.
- For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods.
- For female participants, without reproductive potential may be enrolled if post-menopausal, unless receiving a hormonal therapy for her menopause 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.
Sites / Locations
- North Central Neurology Associates
- Alabama Neurology Associates
- 21st Century Neurology
- Profound Research, LLC
- Stanford University Medical Center; Stanford Neuroscience Health Center
- Collaborative Neuroscience Network Inc.
- Mountain Neurological Research Center; Roaring Fork Neurologt, P.C.
- Advanced Neurology of Colorado, LLC
- Neurology Associates, PA; Research Department
- University of South Florida
- American Health Network Institute, LLC
- University of Kansas Medical Center
- The NeuroMedical Clinic of Central Louisiana
- Maine Medical Center
- Dragonfly Research, LLC
- Henry Ford Health System
- Washington University School of Medicine
- Cleveland Clinic Lou Ruvo; Center for Brain Research
- Dent Neurological Institute
- UC Health Neurology
- Oklahoma Medical Research Foundation; MS Center of Excellence
- Abington Neurological Associates
- Tri-State Mountain Neurology
- Hope Neurology
- Bhupesh Dihenia M.D. P.A.
- Neurology Center of San Antonio
- Evergreen MS Center
- Centro de Especialidades Neurológicas y Rehabilitación - CENyR
- CEMIC
- Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY
- Austin Hospital; Department of Neurology
- Hospital Erasme
- Revalidatie en MS Centrum
- Instituto de Neurologia de Curitiba
- IMV Pesquisa Neurológica
- Clinica Neurologica; Neurocirurgica de Joinville
- CPQuali Pesquisa Clinica Ltda
- Recherche Sepmus Inc.
- Hotel-Dieu de Levis
- Rigshospitalet Glostrup; Neurologisk Klinik
- Groupe Hospitalier Pellegrin; Service de Neurologie - 3ème étage
- CHU Hopital Gabriel Montpied; Service de Neurologie
- CH St Vincent de Paul
- Hôpital Charles Nicolle; Service de Neurologie
- Charite - Universitätsmedizin Berlin
- St. Josef-Hospital, Klinik für Neurologie
- Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
- Universitätsklinikum Schleswig-Holstein; Klinik für Neurologie
- Universität Leipzig; Innere Medizin, Neurologie, Dermatologie
- PANAKEIA - Arzneimittelforschung Leipzig GmbH
- Universitätsklinikum Tübingen, Zentrum für Neurologie
- Universitätsklinikum Ulm; Klinik für Neurologie
- Deutsche Klinik für Diagnostik; DKD Helios Klinik Wiesbaden, Abt. Neurologie
- 401 Military Hospital of Athens; Neurology Department
- AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept.
- S-Medicon Egeszsegugyi Szolgaltato Kft.
- UNO Medical Trials Kft.
- Somogy Vármegyei Kaposi Mór Oktató Kórház
- Universita? G. D'Annunzio; Dipartimento di Neuroscienze, Imaging e Scienze Cliniche
- AOU Seconda Università degli Studi; Dip. Assistenziale Integrato Medicina Int-II Clinica Neurologica
- AOU Seconda Università degli Studi; Dip.Assistenziale Integrato Medicina Int-I Clinica Neurologica
- Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
- NCL Institute Neuroscience
- Policlinico Umberto I; Centro Sclerosi Multipla DAI Neuroscienze e Salute Mentale
- Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari
- IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla
- Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion
- Clinica Internacional; Unidad De Investigacion
- Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia
- Instituto Nacional de Ciencias Neurológicas - Hospital Mogrovejo; Peru
- Hospital Maria Auxiliadora
- Clinica Sanchez Ferrer
- Neurocentrum Bydgoszcz sp. z o.o
- COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny
- MA-LEK Clinical Sp. Z o.o.
- SPZOZ Uniwersytecki Szp. Klin. nr1 im.N.Barlickiego UM;Oddzial Kliniczny Neurologii
- Centrum Neurologii Krzysztof Selmaj
- Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
- Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
- EMC Instytut Medyczny SA
- Nzoz Palomed
- Osrodek Badan Klinicznych Euromedis
- Centrum Medyczne NeuroProtect
- Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
- Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
- Wojskowy Instytut Medyczny - Pa?Stwowy Instytut Badawczy
- Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)
- Centro Hospitalar de Lisboa Ocidental - Hospital Egas Moniz; Neurologia
- Hospital de Santa Maria; Servico de Neurologia
- FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
- National Center of Social Significant Disease
- Neiro Clinica LLC
- Research Center of Neurology of RAMS
- Federal center of brain research and neurotechnologies
- City Clinical Hospital #24; Multipal Sclerosis department
- N.P. Bechtereva Institute of the Human Brain
- City Hospital #40 of Kurortniy Administrative District
- SHI Sverdlovsk Regional Clinical Hospital #1;Neurology
- Vertebronevrologiya LLC
- KSMU Interregional Clinical Diagnostic Centre
- Ulyanovsk Regional Clinical Hospital
- Saratov State Medical University of RosZdrav; Neurology
- Nebbiolo Center for Clinical Trials
- Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Neurologia
- Hospital Quiron de Madrid; Servicio de Neurologia
- Hospital Alvaro Cunqueiro; Servicio de Neurologia
- Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
- Hospital Puerta del Mar; Sevicio de Neurologia
- Hospital Regional Universitario de Malaga ? Hospital General; Servicio de Neurologia
- Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik
- Inselspital Bern Medizin Neurologie; Neurologische Poliklinik
- Ospedale Regionale di Lugano - Civico; Neurologia
- Kocaeli University Hospital; Department of Neurology
- Medical Center Dopomoga Plus
- Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
- Zaporizhia City Multispecialty Clinical Hospital #9
- Municipal Nonprofit Enterprise of Kharkiv Regional Council Regional Clinical Hospital
- 5th Cherkasy City Center of Primary Health Care
- SI USSRI of Medical and Social Problems of Disabilities of MOHU
- Medical Center of Private Execution First Private Clinic
- Lvivska oblasna tsentralna likarnia
- Mun.Med.Proph.Inst.?Chernihiv Reg.Hosp.?; Neurology Department
- Bukovinsky SMU RMI Chernivtsi RCH
- Regional Clinical Hospital; Neurology Department
- St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis
- Derriford Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Ocrelizumab Higher Dose
Ocrelizumab Approved Dose
Participants will be randomized to receive a minimum of 5 higher treatment doses (1200 mg or 1800 mg) of ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the double blind treatment (DBT) phase. 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). 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.
Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by intravenous (IV) infusion every 24 weeks 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.