Progressive Multiple Sclerosis MS
Conditions
Interventions
The investigational medicinal product (IMP) for this study is Ocrelizumab IV (OCREVUS).
The investigational medicinal product (IMP) for this study is Ocrelizumab IV (OCREVUS). recombinant humanized monoclonal antibody.
Sponsors
F. HOFFMANN-LA ROCHE LTD
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: Inclusion Criteria -Patients must meet the following criteria for study entry: -Signed Informed Consent Form. -Able to comply with the study protocol, in the Investigator’s judgment. -Age 18?65 years, inclusive at screening. -Have a definite diagnosis of PMS (as per the revised McDonald 2010 criteria for PPMS* or Lublin et al. 2014 criteria for PMS*). EDSS =6.5 at screening. -Have a length of disease duration since PMS disease symptom onset =10 years if baseline EDSS =5.0 and =15 years if baseline EDSS >5.0. -Have documented evidence of disability progression independent of relapse activity 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 (Appendix 3Appendix 3Appendix 3Appendix 3). -Have experience of having used a smartphone and connecting a smartphone to Wi-Fi network providers. -For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months after the last dose of study drug. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (=12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The following are acceptable contraceptive methods: progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, and cap, diaphragm, or sponge with spermicide. A combination of male condom with cap, diaphragm, or sponge with spermicide (double-barrier methods) is considered acceptable. *For both, PPMS patients according to revised McDonald 2010 criteria and RMS patients meeting criteria for PMS disease course as per Lublin et al. 2014, it will be documented whether or not they fulfill each of the three following McDonald Criteria: 1. Evidence for Dissemination in space (DIS) in the brain based on =1 T2 lesions in at least one area characteristic for MS (periventricular, juxtacortical, or infratentorial). 2. Evidence for DIS in the spinal cord based on =2 T2 lesions in the cord. 3. Positive findings in a cerebrospinal fluid (CSF) specimen (isoelectric focusing evidence of oligoclonal bands and/or elevated immunoglobulin (Ig) G index) [If a recent CSF sample or results from a previous CSF test from each patient is not available, this data will be considered missing information].
Exclusion criteria
Exclusion criteria: Exclusion Criteria: Patients who meet any of the following criteria will be excluded from study entry: -Relapsing-remitting multiple sclerosis (RRMS) at screening. -Inability to complete an MRI (contraindications for MRI include but are not restricted to pacemaker, cochlear implants, presence of foreign substances in the eye, intracranial vascular clips, surgery within 6 weeks of entry into the study, coronary stent implanted within 8 weeks prior to the time of the intended MRI, claustrophobia, weight >140 kg etc.). -Gadolinium (Gd) intolerance -Known presence of other neurological disorders, including but not limited to, the following: -History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack) or ischemia of the spinal cord. -History or known presence of CNS or spinal cord tumor (e.g., meningioma, glioma). -History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency). -History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, human T-lymphotropic virus 1 (HTLV-1), herpes zoster myelopathy). -History of genetically inherited progressive CNS degenerative disorder (e.g., hereditary paraparesis; MELAS [mitochondrial myopathy, encephalopathy, lactic acidosis, stroke] syndrome). -Neuromyelitis optica. -History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, anti-phospholipid antibody syndrome, Sjogren’s syndrome, Behçet’s disease, sarcoidosis). -History of severe, clinically significant brain or spinal cord trauma (e.g., cerebral contusion, spinal cord compression). Exclusions Related to General Health -Pregnancy or lactation. -Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. -History or currently active primary or secondary immunodeficiency. -Lack of peripheral venous access. -Hypersensitivity to ocrelizumab or to any of its excipients. -Significant or uncontrolled somatic disease or any other significant disease that may preclude patient from participating in the study. -Active infections must be treated and resolved before possible inclusion in the study. -Patients in a severely immunocompromised state until the condition resolves -Patients with known active malignancies or being actively monitored for recurrence of malignancy -Patients who have or have had confirmed progressive multifocal leukoencephalopathy (PML) Exclusions Related to Medications: -All vaccines should be given at least 6 weeks before the first infusion of ocrelizumab. Live/live attenuated vaccines should be avoided during treatment and safety follow-up period until B cells are peripherally repleted. -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 (e.g., treatment for chronic cerebrospinal venous insufficiency) within 24 weeks of screening (Visit 1). -Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, tabalumab, belimumab, ofatumumab, or obinutizumab). -Any previous treatment with alemtuzumab (Campath/Mabcampath/Lemtrada), total body irradiation, or bone marrow transplantation. -Previous treatment with natalizumab, daclizumab or fingolimod in the last 8 weeks. -Previous treat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course.;Timepoints: Proportion of patients with no evidence of progression (NEP) ;Measure: Defined as no progression sustained for at least 24 weeks on all of the following three components (CDP#; =20% increase in T25FWT; =20% increase in 9HPT) from baseline to Week 96, Week 96 to Week 192 and baseline to Week 192;Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course.;Timepoints: Proportion of patients with no evidence of progression and no active disease (NEPAD);Measure: 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 from baseline to Week 96, Week 96 to Week 192 and baseline to Week 192 | — |
Secondary
| Measure | Time frame |
|---|---|
| Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course ;Timepoints: Change from baseline in cognitive function ;Measure: as measured by the symbol digit modalities test (SDMT) [as part of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery] ;Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course ;Timepoints: Mean change from baseline in the EDSS score over the course of the study;Measure: NA;Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course ;Timepoints: Time to onset of first CDP sustained for at least 24 and 48 weeks ;Measure: NA;Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course ;Timepoints: Time to onset of first =20% increase in T25FWT sustained for at least 24 weeks ;Measure: NA;Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course ;Timepoints: Time to onset of first =20% increase in 9HPT sustained for at least 24 weeks ;Measure: NA;Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course ;Timepoints: Proportion of patients with NEP ;Measure: defined above from Week 24 to Week 96, Week 24 to Week 192 and Week 48 to Week 192;Name: To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course ;Timepoints: Proportion of patients with NEPAD;Measure: defined above from Week 24 to Week 96, Week 24 to Week 192 and Week 48 to Week 192 ;Name: To evaluate the effectiveness of ocrelizumab treatment in PMS patients using a range of patient- relevant measures;Timepoints: Change from baseline in the following patient-reported outcomes (PROs): – Multiple Sclerosis Impact Scale (MSIS-29) – Multiple Sclerosis Walking scale (MSWS-12) – ABILHAND-56 Questionnaire – Fatigue scale for Motor and cognitive function (FSMC) – SymptoMScreen – 88-item Mul | — |
Countries
Bosnia and Herzegovina, Brazil, Canada, Colombia, Costa Rica, Czech Republic, Denmark, Egypt, France, Guatemala, Hungary, Ireland, Italy, Lebanon, Mexico, Morocco, Netherlands, Panama, Poland, Russian Federation, Spain, United Arab Emirates, United States of America
Contacts
Public ContactSamia Khoury
Nehme and Therese Tohme Multiple Sclerosis Center - American University of Beirut Medical Center
Outcome results
None listed