Ocrelizumab: Ocrelizumab will be administered via intravenous (IV) infusion at an initial dose of two 300-mg infusions separated by 14 days (on Days 1 and 15), and then 600 mg at every subsequent dose every 24 weeks for the remainder of the study treatment period (approximately 192 weeks)
Study summary
This study is a prospective, multicenter, open-label, single-arm effectiveness and safety study in participants with progressive multiple sclerosis (PMS).
Eligibility
Sex
ALL
Min age
18 Years
Max age
65 Years
Healthy volunteers
No
Inclusion Criteria:
* Have a definite diagnosis of PMS (as per the revised McDonald 2010 criteria for PPMS or Lublin et al. 2014 criteria for PMS)
* EDSS (Expanded Disability Status Scale) \</ =6.5 at screening
* Have a documented evidence of disability progression independent of relapse at any point over the 2 years prior to the screening visit. In case relapse(s) have occurred in the last 2 years, disability progression will have to be considered as independent of relapse activity as per treating physician's judgment
* Fulfill at least one of the 21 criteria assessing the evidence of disability progression independent of relapse activity in the last 2 years using the pre-baseline disability progression rating system checklist
* Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers
* For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 6 months, or longer if the local label is more stringent after the last dose of study drug
Exclusion Criteria:
* Relapsing-remitting multiple sclerosis (RRMS) at screening
* Inability to complete an MRI
* Gadolinium (Gd) intolerance
* Known presence of other neurological disorders
Exclusions Related to General Health:
* Pregnancy confirmed by positive serum β human chorionic gonadotropin (hCG) measured at screening
* Lactation
* Any concomitant disease that may require chronic treatment of systemic corticosteroids or immunosuppressants during the course of the study
* History or currently active primary or secondary immunodeficiency
* Lack of peripheral venous access
* Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study.
* Active infections must be treated and resolved prior to the first infusion of ocrelizumab
* Participants in a severely immunocompromised state until the condition resolves
* Participants with known active malignancies or being actively monitored for recurrence of malignancy
* Participants who have or have had confirmed progressive multifocal leukoencephalopathy (PML)
Exclusions Related to Laboratory Findings:
* Positive screening tests for hepatitis B
* CD4 count \<250/μL
* ANC \<1.0 × 103/μL
* AST/SGOT or ALT/SGPT ≥3.0 × ULN in combination with either an elevated total bilirubin (\>2 X ULN) or clinical jaundice
Exclusions Related to Medications:
* Hypersensitivity to ocrelizumab or to any of its excipients
* Previous treatment with ocrelizumab
* Previous treatment with B-cell targeted therapies (i.e., atacicept, tabalumab, belimumab, ofatumumab, or obinutuzumab). Note: previous treatment with rituximab is allowed as long as the last dose was administered more than 6 months before the ocrelizumab infusion AND if discontinuation was due to adverse events or immunogenicity AND if Bcell levels are above the lower limit of normal (LLN) prior to screening.
* Any previous treatment with alemtuzumab (Campath/Mabcampath/Lemtrada), total body irradiation, or bone marrow transplantation
* Previous treatment with natalizumab where PML has not been excluded according to specific algorithm
* Contraindications to or intolerance of oral or intravenous (IV) corticosteroids, including methylprednisolone administered IV, according to the country label
* Systemic corticosteroid therapy within 4 weeks prior to screening
* All vaccines should be given at least 6 weeks before the first infusion of ocrelizumab, unless the local regulations allow for a shorter interval. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted
* Previous treatment with daclizumab, ozanimod or figolimod in the last 8 weeks
* Previous treatment with siponimod in the last 2 weeks
* Treatment with fampridine/dalfampridine (Fampyra)/Ampyra) or other symptomatic MS treatment unless on stable dose for ≥30 days prior to screening
* Previous treatment with natalizumab in the last 12 weeks.
* Previous treatment with teriflunomide in the last 12 weeks. This washout period can be shortened if an accelerated elimination procedure is implemented before screening visit. One of the following elimination procedures can be used:
* Cholestyramine 8 g administered 3 times daily for a period of at least 7 days (cholestyramine 4 g three times a day can be used, if cholestyramine 8 g three times a day is not well tolerated)
* Alternatively, 50 g of activated powdered charcoal is administered every 12 hours for a period of at least 7 days.
* Previous treatment with azathioprine, cyclophosphamide, mycophenolate mofetil or methotrexate in the last 12 weeks
* Treatment with any investigational agent within 24 weeks of screening (Visit 1) or five half-lives of the investigational drug (whichever is longer) or treatment with any experimental procedures for MS
* Previous treatment with mitoxantrone, cyclosporine or cladribine in the last 96 weeks
* Participants previously treated with teriflunomide within the last two years, unless measured plasma concentrations are less than 0.02 mg/l. If above or not known, an accelerated elimination procedure should be implemented before screening visit
Primary outcome measure(s)
Proportion of Participants with No Evidence of Progression (NEP) — From Baseline to Week 96, Week 96 to Week 192 and Baseline to Week 192 NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (confirmed disability progression \[CDP\]; ≥20% increase in timed 25-foot walk test \[T25FWT\]; ≥20% increase in nine-hole peg test \[9HPT\])
Proportion of Participants with no evidence of progression and no active disease (NEPAD) — From Baseline to Week 96, Week 96 to Week 192 and Baseline to Week 192 NEPAD is defined as no progression sustained for at least 24 weeks on all of the three components of NEP (CDP, T25FWT, 9HPT), no protocol-defined relapse, no enlarging or new T2 lesion, and no T1 gadolinium (Gd+)-enhancing lesion
Trial sites (120)
Facility
City
Region
Status
MS Center of California
Laguna Hills
California
SC3 Research Group, Inc
Pasadena
California
University of California San Francisco
San Francisco
California
University of South Florida
Tampa
Florida
University of Chicago
Chicago
Illinois
Massachusetts General Hospital
Boston
Massachusetts
Dragonfly Research, LLC
Wellesley
Massachusetts
Wayne State University School of Medicine
Detroit
Michigan
Washington University School of Medicine
St Louis
Missouri
The MS Center of Northeastern New York
Latham
New York
University of Cincinnati
Cincinnati
Ohio
Neurology Clinic PC
Cordova
Tennessee
Central Texas Neurology Consultants
Round Rock
Texas
Lone Star Neurology of San Antonio
San Antonio
Texas
Swedish Multiple Sclerosis Center
Seattle
Washington
University Clinical Center of the Republic of Srpska
Banja Luka
Bosnia and Herzegovina
University Hospital Mostar
Mostar
Bosnia and Herzegovina
Clinical Center University of Sarajevo
Sarajevo
Bosnia and Herzegovina
University Clinical Center Tuzla
Tuzla
Bosnia and Herzegovina
Instituto de Neurologia de Curitiba
Curitiba
Paraná
Hospital Sao Lucas - PUCRS
Porto Alegre
Rio Grande do Sul
Hospital das Clínicas Faculdades Médicas de Ribeirão Preto
Ribeirão Preto
São Paulo
Hospital das Clinicas - FMUSP_X
São Paulo
São Paulo
Fraser Health Authority - Fraser Health Multiple Sclerosis
Burnaby
British Columbia
University of British Columbia Hospital
Vancouver
British Columbia
London Health Sciences Centre Uni Campus
London
Ontario
St. Michael'S Hospital
Toronto
Ontario
Recherche Sepmus Inc.
Greenfield Park
Quebec
Hospital Notre-Dame du Centre Hospitalier de l'Universite de Montreal
Montreal
Quebec
Saskatoon City Hospital
Saskatoon
Saskatchewan
Organizacion Sanitas Internacional
Bogotá
Colombia
Fundacion Clinica Valle del Lili
Cali
Colombia
Hospital Clínica Biblica
San José
Costa Rica
Nemocnice Jihlava
Jihlava
Czechia
Fakultní Nemocnice Olomouc
Olomouc
Czechia
Fakultni nemocnice Ostrava
Ostrava-Poruba
Czechia
Vseobecna fakultni nemocnice v Praze
Prague
Czechia
Aarhus Universitetshospital
Aarhus N
Denmark
Rigshospitalet
Glostrup Municipality
Denmark
Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken
Sønderborg
Denmark
+ 80 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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