This study is a prospective, multicenter, open-label, single-arm effectiveness and safety study in participants with progressive multiple sclerosis (PMS).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
927
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)
Proportion of Participants with No Evidence of Progression (NEP)
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 \[9HPT\])
Time frame: From Baseline to Week 96, Week 96 to Week 192 and Baseline to Week 192
Proportion of Participants with no evidence of progression and no active disease (NEPAD)
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
Time frame: From Baseline to Week 96, Week 96 to Week 192 and Baseline to Week 192
Change from Baseline in Cognitive Function, as Measured by the Symbol Digit Modalities Test (SDMT)
Time frame: Baseline to end of study (Week 192)
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)
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)
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
Time to Onset of First >=20% Increase in Timed 25-foot Walk Test (T25FWT) Sustained for at least 24 Weeks
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MS Center of California
Laguna Hills, California, United States
SC3 Research Group, Inc
Pasadena, California, United States
University of California San Francisco
San Francisco, California, United States
Yale University
North Haven, Connecticut, United States
University of South Florida
Tampa, Florida, United States
University of Chicago
Chicago, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Dragonfly Research, LLC
Wellesley, Massachusetts, United States
Wayne State University School of Medicine
Detroit, Michigan, United States
Washington University School of Medicine
St Louis, Missouri, United States
...and 114 more locations
Time frame: Baseline to onset of first >=20% increase in T25FWT sustained for at least 24 weeks
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
Proportion of Participants with NEP
Time frame: Week 24 to Week 96, Week 24 to Week 192, and Week 48 to Week 192
Proportion of Participants with NEPAD
Time frame: Week 24 to Week 96, Week 24 to Week 192, Week 48 to Week 192
Change from Baseline in Patient-Reported Outcomes (PROs)
PROs collected in this study will be the Multiple Sclerosis Impact Scale (MSIS-29), the Multiple Sclerosis Walking scale (MSWS-12), the ABILHAND-56 Questionnaire, Fatigue Scale for Motor and Cognitive function (FSMC), SymptoMScreen, 88-item Multiple Sclerosis Spasticity Scale (MSSS-88), Numerical Pain Rating Scale (NPRS), and the Patient Global Impression of Severity (PGIS) for upper limb, lower limb and cognitive function
Time frame: Baseline to end of study (Week 192)
Change from Baseline in the number of falls and near-falls
Time frame: Baseline to end of study (Week 192)
Change in Whole Brain Volume (Whole, Cerebral White Matter, Cortical Grey Matter, Deep grey matter)
Time frame: Baseline to end of study (Week 192)
Change in thalamic volumes
Time frame: Baseline to end of study (Week 192)
Change in whole and regional cerebellar volume (cervical cord grey and white matter area)
Time frame: Baseline to end of study (Week 192)
Change in cervical cord cross-sectional area (total, white matter and grey matter)
Time frame: Baseline to end of study (Week 192)
Change in number of new/enlarging T2 lesions and total T2 Lesion Volume
Time frame: Baseline to end of study (Week 192)
Change in number of T1 Gadolinium (Gd)+ Lesions and total volume
Time frame: 'Baseline to end of study (Week 192)
Change in number of T1 lesions
Time frame: Baseline to end of study (Week 192)
Number in total volume of T1 lesions
Time frame: Baseline to end of study (Week 192)
Change in Slowly Evolving Lesions (SEL)
Time frame: Baseline to end of study (Week 192)
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)
Change in Gd-enhancing late-Fluid-Attenuated Inversion-Recovery (FLAIR) Meningeal Lesions
Time frame: Baseline to end of study (Week 192)
Change in the number/ spatial distribution of lesions in the cervical spinal cord
Time frame: Baseline to end of study (Week 192)
Spectroscopic MR: Measure of the Relative Signal Amplitude of N-Acetyl Aspartate (NAA), and Choline to Creatine
Only in centers with 1.5-Tesla MRI capable to perform it
Time frame: Baseline to end of study (Week 192)
Measure of phase rim lesions using a Susceptibility-Weighted Imaging [SWI]/T2 sequence
Only in centers with 3-Tesla MRI capable to perform it, where this sequence would replace the spectroscopic MR in the acquisition flow
Time frame: Baseline to end of study (Week 192)
Percentage of Participants with Adverse Events (AEs)
Time frame: Baseline to end of study (Week 192)
Rates of study treatment discontinuation due to adverse events
Time frame: Baseline to Week 192