Active, not recruiting
Phase 3
A Study to Evaluate Ocrelizumab Treatment in Participants With Progressive Multiple Sclerosis
Condition(s) studied
Progressive Multiple Sclerosis (PMS)
Investigational drug(s) / intervention(s)
Ocrelizumab
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
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.