Progressive multiple sclerosis (PMS) MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders MedDRA version: 21.1 Level: PT Classification code 10053395 Term: Progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age 18-65 years - Have a definite diagnosis of PMS (as per the revised McDonald 2010 criteria for PPMS or Lublin et al. 2014 criteria for PMS) - Expanded Disability Status Scale (EDSS) =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Relapsing-remitting multiple sclerosis (RRMS) at screening. - Inability to complete an MRI - Gadolinium (Gd) intolerance - Known presence of other neurological disorders, including but not limited to, the following: o History of ischemic or haemorrhagic disorders of the brain or the spinal cord o History or known presence of Central nervous system (CNS) or spinal cord tumour, or potential metabolic causes of myelopathy or infectious causes of myelopathy or systemic autoimmune disorders potentially causing progressive neurologic disease o History of genetically inherited progressive CNS degenerative disorder o Neuromyelitis optica. o History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease o History of severe, clinically significant brain or spinal cord trauma Exclusions Related to General Health: - Pregnancy or Lactation - Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressant’s during the course of the study - History of 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 the patient from participating in the study - Active infections must be treated and resolved prior to the first infusion of ocrelizumab - 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 Absolute exclusions: - Previous treatment with ocrelizumab - Hypersensitivity to ocrelizumab or to any of its excipients - Previous treatment with B-cell targeted therapies 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 B-cell levels are above the lower limit of normal (LLN) prior to screening - Any previous treatment with alemtuzumab, total body irradiation, or bone marrow transplantation. - Previous treatment with natalizumab where PML has not been excluded according to a specific algorithm - Contraindications to or intolerance of oral or intravenous (IV) corticosteroids Relative exclusions: 4 to 8 weeks prior to screening - 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 or fingolimod in the last 8 weeks - Treatment with fampridine/dalfampridine or other symptomatic MS treatment unless on stable dose for >=30 days prior to screening. Wherever possible, patients should remain on stable doses throughout the treatment period 12 weeks prior to screening - Previous treatment with natalizumab, azathioprine, cyclophosphamide, mycophenolate mofetil or methotrexate in the last 12 weeks 24 weeks prior to screening - Treatment with any investigational agent within 24 weeks of screening or five half-lives of the investigational drug or treatment (whichever is longer) with any experimental proced
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the effectiveness of ocrelizumab treatment in patients with PMS disease course;Secondary Objective: •To evaluate the effectiveness of ocrelizumab treatment in PMS patients using a range of patient-relevant measures and imaging outcomes •To evaluate the safety and tolerability of ocrelizumab in PMS patients ;Primary end point(s): 1. Proportion of patients with no evidence of progression (NEP) sustained for at least 24 weeks 2. Proportion of patients with NEP and no active disease (NEPAD) sustained for at least 24 weeks ;Timepoint(s) of evaluation of this end point: 1-2. From baseline to Week 96, Week 96 to Week 192 and baseline to Week 192 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change from baseline in cognitive function as measured by the Symbol Digit Modalities Test (SDMT) and the Brief Visuospatial Memory Test – Revised (BVMT-R) 2. Change from baseline in the patient-reported outcomes including Multiple Sclerosis Impact Scale -29, Multiple Sclerosis Walking scale -12 items, ABILHAND-56 Questionnaire, Fatigue Scale for Motor and Cognitive (FSMC) function, SymptoMScreen, 88-item Multiple Sclerosis Spasticity Scale, Numerical Pain Rating Scale, Patient Global Impression of Severity (PGIS) for upper limb, lower limb and cognitive functions 3. Mean change from baseline in the EDSS score over the course of the study 4. Time to onset of first confirmed disability progression (as measured by EDSS) sustained for at least 24 and 48 weeks 5. Time to onset of first >=20% increase in timed 25-foot walk test sustained for at least 24 weeks 6. Time to onset of first >=20% increase in 9-hole peg test sustained for at least 24 weeks 7. Proportion of patients with NEP 8. Proportion of patients with NEPAD 9. Proportion of patients with confirmed disability improvement sustained for at least 24 weeks 10. Change in the following MRI volumetric measures: whole brain volume, cerebral white matter volume change, cortical gray matter volume, deep grey matter volume, thalamic volumes, whole and regional cerebellar volume 11. Change in the following lesion and tissue integrity parameters: • Number of new/enlarging T2 lesions and Total T2 lesion volume • Number of T1 Gd+ lesions and total volume • Number of T1 lesions and total volume • Gd-enhancing fluid-attenuated inversion-recovery (FLAIR) meningeal lesions 12. Rate and nature of adverse events 13. Changes in clinical laboratory results 14. Rates of study treatment discontinuation due to adverse events 15. Change in the number of falls and near-falls;Timepoint(s) of evaluation of this end point: 1-3. From baseline to Weeks 48, 96, 144, 192 4-6. From baseline to Week 192 7-8. From We | — |
Countries
Algeria, Bosnia and Herzegovina, Brazil, Canada, Colombia, Costa Rica, Czechia, Czech Republic, Denmark, Egypt, France, Germany, Guatemala, Hungary, Ireland, Italy, Lebanon, Mexico, Morocco, Netherlands, Panama, Poland, Russian Federation, Spain, United Arab Emirates
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed