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Key inclusion & exclusion criteria
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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)
- 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 ß 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
Age minimum:
18 Years
Age maximum:
65 Years
Gender:
All
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Secondary Outcome(s)
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Change from Baseline in Cognitive Function, as Measured by the Symbol Digit Modalities Test (SDMT)
[Time Frame: Baseline to end of study (Week 192)]
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Change in number of T1 Gadolinium (Gd)+ Lesions and total volume
[Time Frame: 'Baseline to end of study (Week 192)]
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Change in Slowly Evolving Lesions (SEL)
[Time Frame: Baseline to end of study (Week 192)]
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Change in cervical cord cross-sectional area (total, white matter and grey matter)
[Time Frame: Baseline to end of study (Week 192)]
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Change from Baseline in the number of falls and near-falls
[Time Frame: Baseline to end of study (Week 192)]
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Change in thalamic volumes
[Time Frame: Baseline to end of study (Week 192)]
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Change in the number/ spatial distribution of lesions in the cervical spinal cord
[Time Frame: Baseline to end of study (Week 192)]
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Change in Whole Brain Volume (Whole, Cerebral White Matter, Cortical Grey Matter, Deep grey matter)
[Time Frame: Baseline to end of study (Week 192)]
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Change from Baseline in Cognitive Function, as Measured by Brief Visuospatial Memory Test - Revised (BVMT-R)
[Time Frame: Baseline to end of study (Week 192)]
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Rates of study treatment discontinuation due to adverse events
[Time Frame: Baseline to Week 192]
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Spectroscopic MR: Measure of the Relative Signal Amplitude of N-Acetyl Aspartate (NAA), and Choline to Creatine
[Time Frame: Baseline to end of study (Week 192)]
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Change in normalised T1 intensity/T1 Gd+ enhancement in New Focal T2 Lesions, SELs, Persistent Areas of Non-SEL T2 Lesions, and Normal-Appearing Brain Tissue
[Time Frame: Baseline to end of study (Week 192)]
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Time to Onset of First >=20% Increase in Timed 25-foot Walk Test (T25FWT) Sustained for at least 24 Weeks
[Time Frame: Baseline to onset of first >=20% increase in T25FWT sustained for at least 24 weeks]
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Time to Onset of First Confirmed Disability Progression (CDP) Sustained for at least 24 and 48 Weeks
[Time Frame: Baseline to onset of first CDP (as measured by EDSS) sustained for at least 24 and 48 weeks]
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Proportion of Participants with NEP
[Time Frame: Week 24 to Week 96, Week 24 to Week 192, and Week 48 to Week 192]
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Change in number of new/enlarging T2 lesions and total T2 Lesion Volume
[Time Frame: Baseline to end of study (Week 192)]
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Change in whole and regional cerebellar volume (cervical cord grey and white matter area)
[Time Frame: Baseline to end of study (Week 192)]
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Change from Baseline in Patient-Reported Outcomes (PROs)
[Time Frame: Baseline to end of study (Week 192)]
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Proportion of Participants with NEPAD
[Time Frame: Week 24 to Week 96, Week 24 to Week 192, Week 48 to Week 192]
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Time to Onset of First >=20% Increase in 9 Hole Peg Test (9HPT) Sustained For At Least 24 Weeks
[Time Frame: Baseline to onset of first >=20% increase in 9HPT sustained for at least 24 weeks]
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Number in total volume of T1 lesions
[Time Frame: Baseline to end of study (Week 192)]
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Change in Gd-enhancing late-Fluid-Attenuated Inversion-Recovery (FLAIR) Meningeal Lesions
[Time Frame: Baseline to end of study (Week 192)]
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Change in number of T1 lesions
[Time Frame: Baseline to end of study (Week 192)]
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Mean Change from Baseline in the Expanded Disability Status Scale (EDSS) score over the course of the study
[Time Frame: Baseline to end of study (Week 192)]
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Measure of phase rim lesions using a Susceptibility-Weighted Imaging [SWI]/T2 sequence
[Time Frame: Baseline to end of study (Week 192)]
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Percentage of Participants with Adverse Events (AEs)
[Time Frame: Baseline to end of study (Week 192)]
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