Multiple Sclerosis, Relapsing-Remitting
Conditions
Brief summary
This is a prospective, multicenter, open-label, single-arm, phase 3b study which evaluates effectiveness and safety of ocrelizumab in participants with early stage RRMS. The study will consist of an open-label treatment period of 192 weeks and follow-up period of at least 48 weeks. The optional shorter infusion substudy will evaluate the safety of a shorter infusion of ocrelizumab in a subgroup of participants with early stage RRMS enrolled in the main MA30143 study. Approximately 700 patients will be enrolled in the substudy, and will receive additional 600 mg ocrelizumab administered in a shorter time frame.
Interventions
DRUGOcrelizumab
Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Have a definite diagnosis of RRMS, as per the revised McDonald 2010 criteria * Have a length of disease duration, from first documented clinical attack consistent with MS disease of less than or equal to (\</=) 3 years * Within the last 12 months one or more clinically reported relapse(s) or one or more signs of MRI activity * EDSS of 0.0 to 3.5 inclusive, at screening * An agreement to use an acceptable birth control method for women of childbearing potential, during the treatment period and for at least 6 months or longer after the last dose of study drug
Exclusion criteria
* Secondary progressive multiple sclerosis or history of primary progressive or progressive relapsing MS * Inability to complete an MRI * Known presence of other neurological disorders Exclusions Related to General Health: * Pregnancy or lactation * Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug * 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 * History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies * Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study * Congestive heart failure (New York Heart Association III or IV functional severity) * Known active bacterial, viral, fungal, mycobacterial infection or other infection, (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or oral antibiotics 2 weeks prior to screening * History of malignancy, major opportunistic infections, alcohol or drug abuse, recurrent or chronic infection, and/or coagulation disorders Exclusions Related to Medications: * Received any prior approved disease modifying treatment (DMT) with a label for MS, for example, interferons, glatiramer acetate, natalizumab, alemtuzumab, daclizumab, fingolimod, teiflunomide and dimethylfumarate * Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit * Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab) * Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic therapies (cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, cladribine, mitoxantrone, laquinimod, total body irradiation, or bone marrow transplantation) * Treatment with investigational DMT * Treatment with fampridine/dalfamipridine unless on stable dose for \>/=30 days prior to screening Exclusion related to Shorter Infusion Substudy: \- Any previous serious IRRs experienced with ocrelizumab treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS) | Baseline up to 4 years | The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits for a minimum of 24 weeks/48 weeks. |
| Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS | At Weeks 24 and 48 during Year 1 | CDI is defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). |
| Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS | Year 1 (Weeks 24 and 48) | The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here. |
| Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS | At Weeks 48, 72 and 96 during Year 2 | CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). |
| Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS | Year 2 (Weeks 72 and 96) | The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here. |
| Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS | At Weeks 144, 168 and 192 during Year 4 | CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). |
| Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS | Year 4 (Weeks 168 and 192) | The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here. |
| Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS | Year 1 (Week 48) | — |
| Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS | Year 2 (Week 96) | — |
| Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS | Year 3 | — |
| Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS | Year 4 | — |
| Mean Change From Baseline in EDSS Score at Week 24 | From Baseline to Week 24 | — |
| Mean Change From Baseline in EDSS Score at Week 48 | From Baseline to Week 48 | — |
| Mean Change From Baseline in EDSS Score at Week 72 | From Baseline to Week 72 | — |
| Mean Change From Baseline in EDSS Score at Week 96 | Baseline, Week 96 | — |
| Mean Change From Baseline in EDSS Score at Week 120 | Baseline, Week 120 | — |
| Mean Change From Baseline in EDSS Score at Week 144 | Baseline, Week 144 | — |
| Mean Change From Baseline in EDSS Score at Week 168 | Baseline, Week 168 | — |
| Mean Change From Baseline in EDSS Score at Week 192 | Baseline, Week 192 | — |
| Percentage of Participants Without Protocol-Defined Event of Disease Activity | Baseline up to 4 years | Protocol-defined event of disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis \[MS\], as determined using EDSS/Functional Systems Score \[FSS\] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8 (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan. |
| Percentage of Participants Without Relapse | Baseline up to 4 years | Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. |
| Annualized Relapse Rate | Baseline up to 4 years | Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. The adjusted annualized relapse rate is reported which is: Adjusted by age at disease diagnosis, Baseline EDSS, Presence of T1 Gd-enhanced lesion at screening and Presence of relapses in the last year prior to enrollment. Log-transformed exposure time is included as an offset variable. The report contains data up to week 192 of the treatment period of each individual participant. |
| Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy | Week 24 through Week 144 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Substudy: Number of IRR Symptoms | From Week 24 to Week 144 | — |
| Percentage of Participants Who Are Relapse Free | Week 192 | Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. |
| Substudy: IRRs Leading to Treatment Discontinuation | From Week 24 to Week 144 | — |
| Percentage of Participants With No Evidence of Protocol Defined Disease Activity | Weeks 96, 144, 192 | Protocol-defined disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis \[MS\], as determined using EDSS/Functional Systems Score \[FSS\] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8. (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan. Event-free rate |
| Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP) | Weeks 96, 192 | NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20 percent \[%\] increase from baseline in timed 25 Foot Walk Test \[T25FWT\]; 20% increase from baseline in timed 9 hole peg test \[9HPT\]). CDP will be assessed using EDSS. |
| Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) | Weeks 96, 192 | NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion. CDP will be assessed using EDSS. Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. |
| Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Weeks 24, 48, 72, 96, 120, 144, 168, 192 | MSFC combines the following: Timed 25 Foot Walk Test \[T25FWT\] for leg function &ambulation measured in seconds (sec). The longer it takes to walk, higher the score indicating deterioration; 9 Hole Peg Test \[9HPT\] for arm & handf unction measured in sec. Higher score=more time taken to complete test indicating deterioration. Paced Auditory Serial Addition Test \[PASAT\] for cognitive function (score range: 0-60, higher score=better cognitive processing speed). MSFC composite={\[Average(1/9-HPT)-Baseline Mean(1/9-HPT)/Baseline Std Dev(1/9-HPT)\]+\[-(Average T25FWT-Baseline Mean T25FWT)/Baseline Std-Dev T25FWT\]+\[(PASAT-3-BaselineMean PASAT-3)/Baseline Std Dev PASAT-3\]}/ 3.0. MSFC is based on the concept that scores for these 3 dimensions are combined to create a single score to detect change over time in a group of MS patients. Higher composite score=better overall function. Lower score=worse overall function. Higher mean change in total MSFC score=functional improvement at cohort level. |
| Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 | The change in the mean score of T25FW is reported below. The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, the higher score, which indicates deterioration. Lower times indicate better performance and greater mobility. Higher times indicate worse performance and greater impairment. Subsequently, the lower the mean change in the score over time, the better performance. |
| Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Weeks 24, 48, 72, 96, 120, 144, 168, 192 | The mean change in 9 Hole Peg Test (9HPT)-score is reported. Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. The number of seconds it takes to complete the test, the higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance. |
| Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Weeks 24, 48, 72, 96, 120, 144, 168, 192 | Mean change in the Paced Auditory Serial Addition Test \[PASAT\] score is reported. PASAT measures cognitive function. A total of 60 single digit numbers are presented by an audiotape/CD-rom at a constant rate in every 3 seconds (PASAT-3). Participants are required to add each new number to the one immediately before it. Due to the relative complexity of this test, a practice trial with a set of 10 numbers should be performed before the original test. Participants are allowed up to 3 practice trials. Two sets of numbers (forms A & B) are developed to be used alternatively in every visit to minimize memorizing. The number of correct answers is recorded. The PASAT score ranges from 0 to 60, with higher values representing a better outcome in cognitive processing speed. Subsequently, higher values in mean changes from baseline over the study time indicate improvement in cognitive function. |
| Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) | Baseline, Weeks 48, 96, 144, 192 | BICAMS is assessing cognitive processing speed and verbal and visual memory. SDMT assesses processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 second time span. The higher the results, the better processing speed/working memory. |
| Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) | Baseline, Weeks 48, 96, 144, 192 | BICAMS assesses cognitive processing speed and verbal and visual memory. The CLVT-II is an assessment of verbal learning and memory which measures recall and recognition scores, encoding strategies, learning rates and error types. A list learning task with 16 words from 4 semantic categories are read over a series of 5 list presentations. Recall is assessed after learning and at a 20-minute delay. The maximum possible score is 80 and a minimum is 0. A higher score indicated better recall. |
| Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) | Baseline, Weeks 48, 96, 144, 192 | BICAMS assesses cognitive processing speed and verbal and visual memory. BVMT-R assesses visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory. |
| Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Weeks 24, 48, 96, 144, 192 | Number of Lesions are categorized as followed: 1, 2, 3, \>1, \>3 |
| Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Baseline, Weeks 24, 48, 96, 144, 192 | Number of Lesions are categorized as followed: 1, 2, 3, \>1 |
| Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI | Baseline, Weeks 48, 96, 144, 192 | — |
| Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Baseline, Weeks 8, 24, 48, 96, 144, 192 | Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI was measured for its volumes. |
| Change From Baseline in Brain Volume as Detected by Brain MRI | From Baseline to Weeks 24, 48, 96, 144, 192 | Percentage change from Normalized brain volume in cm3 (cubic centimeter)values are reported |
| Percentage of Participants Without Treatment Discontinuation | Baseline up to 4 years | — |
| Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Baseline, Weeks 24, 48, 96, 120, 144, 192 | WPAI scale measures impact of health problems on work productivity and regular activities: Absenteeism (Work Time Missed) measuring % of work time missed due to health issues; Presenteeism:Calculated as the percentage of impairment while working due to health problems. Overall Work Impairment:Calculated by combining absenteeism and presenteeism using the formula:Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism This formula accounts for both the time missed and the reduced productivity while at work. Activity Impairment: Calculated as the percentage of impairment in regular activities outside of work. Range: Each component is scored as 0%-100%). Higher % indicate greater impairment and worse outcomes. |
| SymptoMScreen Composite Score | Baseline, Weeks 24, 48, 96, 144, 192 | The SMSS consists of 12 items which are assessed on a seven-point Likert scale that ranges from 0 (not at all affected) to 6 (total limitation) \[7\]. The total score ranges from 0 to 72, with higher scores indicating more severe symptom endorsement. |
| Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score | Baseline, Weeks 24, 48, 96, 144, 192 | The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a questionnaire to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective, which includes 29 items self-reported measures associated with a physical scale and 9 items with a psychological scale. MSIS-29 scales are generated by summing items and it's ranging from 29-145'. The higher total MSIS-29 scores indicate a greater degree of disability. The mean change in MSIS-29 scores from baseline is reported. The decreasing values in the mean change from baseline indicate functional improvement from patients' perspective |
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Baseline up to 4 years | — |
| Substudy: Number of Participants With IRR Overall and by Dose at Randomization | From Week 24 to Week 144 | — |
| Substudy: Severity of IRRs | From Week 24 to Week 144 | The number of participants with IRRs by most extreme intensity were reported (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 =life-threatening, grade 5 = fatal). Multiple IRRs in one participant are counted only once at the most extreme (highest) intensity observed. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Croatia, Denmark, France, Germany, Hungary, Italy, Kuwait, Lebanon, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
A prospective, multicenter, open-label, single-arm effectiveness and safety study enrolled 1225 eligible treatment-naive patients with early stage RMSR. The study consisted of screening period up 4 weeks and open-label treatment with ocrelizumab period up to 192 week.
Pre-assignment details
The efficacy analyses were performed on the main study cohort enrolled as per original study protocol, and safety analyses on all enrolled participants.
Participants by arm
| Arm | Count |
|---|---|
| Ocrelizumab Ocrelizumab was administered intravenously (IV) as two 300-milligram (mg) infusions on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period | 1,225 |
| Total | 1,225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Main Study | Adverse Event | 25 | 0 | 0 |
| Main Study | Changed to Commercial Ocrelizumab | 4 | 0 | 0 |
| Main Study | Death | 12 | 0 | 0 |
| Main Study | Disease progression | 1 | 0 | 0 |
| Main Study | Lack of Efficacy | 10 | 0 | 0 |
| Main Study | Lost to Follow-up | 17 | 0 | 0 |
| Main Study | Physician Decision | 13 | 0 | 0 |
| Main Study | Planned pregnancy | 17 | 0 | 0 |
| Main Study | Pregnancy | 7 | 0 | 0 |
| Main Study | Protocol Violation | 15 | 0 | 0 |
| Main Study | Site Closure | 3 | 0 | 0 |
| Main Study | Terminated By Sponsor | 14 | 0 | 0 |
| Main Study | Withdrawal by Subject | 77 | 0 | 0 |
| Substudy (Week 24 to Week 144) | Reason Not Specified | 0 | 13 | 8 |
| Substudy (Week 24 to Week 144) | Substudy Stopped by Sponsor | 0 | 355 | 352 |
| Substudy (Week 24 to Week 144) | Withdrawal by Subject | 0 | 5 | 7 |
| Substudy (Week 24 to Week 144) | Withdrawal due to Infusion Related Reaction (IRR) | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | Ocrelizumab |
|---|---|
| Age, Continuous | 32.7 Years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 145 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 960 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 120 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 11 Participants |
| Race (NIH/OMB) Asian | 19 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants |
| Race (NIH/OMB) More than one race | 37 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 115 Participants |
| Race (NIH/OMB) White | 1007 Participants |
| Sex: Female, Male Female | 784 Participants |
| Sex: Female, Male Male | 441 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 13 / 1,225 | 2 / 370 | 1 / 375 |
| other Total, other adverse events | 1,110 / 1,225 | 251 / 370 | 276 / 375 |
| serious Total, serious adverse events | 184 / 1,225 | 21 / 370 | 19 / 375 |
Outcome results
Primary
Annualized Relapse Rate
Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. The adjusted annualized relapse rate is reported which is: Adjusted by age at disease diagnosis, Baseline EDSS, Presence of T1 Gd-enhanced lesion at screening and Presence of relapses in the last year prior to enrollment. Log-transformed exposure time is included as an offset variable. The report contains data up to week 192 of the treatment period of each individual participant.
Time frame: Baseline up to 4 years
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Annualized Relapse Rate | 0.02 events per participant per year |
Primary
Mean Change From Baseline in EDSS Score at Week 120
Time frame: Baseline, Week 120
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 120 | -0.10 Change in Total EDSS Score | Standard Deviation 0.94 |
Primary
Mean Change From Baseline in EDSS Score at Week 144
Time frame: Baseline, Week 144
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 144 | -0.10 Change in Total EDSS Score | Standard Error 1 |
Primary
Mean Change From Baseline in EDSS Score at Week 168
Time frame: Baseline, Week 168
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 168 | -0.05 Change in Total EDSS Score | Standard Error 1.05 |
Primary
Mean Change From Baseline in EDSS Score at Week 192
Time frame: Baseline, Week 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 192 | -0.06 Change in Total EDSS Score | Standard Deviation 1.06 |
Primary
Mean Change From Baseline in EDSS Score at Week 24
Time frame: From Baseline to Week 24
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 24 | -0.14 Change in Total EDSS Score | Standard Deviation 0.68 |
Primary
Mean Change From Baseline in EDSS Score at Week 48
Time frame: From Baseline to Week 48
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 48 | -0.14 Change in Total EDSS Score | Standard Deviation 0.77 |
Primary
Mean Change From Baseline in EDSS Score at Week 72
Time frame: From Baseline to Week 72
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 72 | -0.09 Change in Total EDSS Score | Standard Deviation 0.89 |
Primary
Mean Change From Baseline in EDSS Score at Week 96
Time frame: Baseline, Week 96
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Mean Change From Baseline in EDSS Score at Week 96 | -0.12 Change in Total EDSS Score | Standard Error 0.95 |
Primary
Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Time frame: Year 1 (Weeks 24 and 48)
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed for CDP at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS | CDP Sustained for 24 weeks: At Week 24 | 99.55 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS | CDP Sustained for 24 weeks: At Week 48 | 97.30 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS | CDP Sustained for 48 weeks: At Week 48 | 98.05 Percentage of Participants |
Primary
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Time frame: Year 2 (Weeks 72 and 96)
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed for CDP at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS | CDP Sustained for 24 weeks: At Week 72 | 93.97 Percentage of Particiopants |
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS | CDP Sustained for 48 weeks: At Week 72 | 95.18 Percentage of Particiopants |
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS | CDP Sustained for 24 weeks: Week 96 | 91.65 Percentage of Particiopants |
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS | CDP Sustained for 48 weeks: Week 96 | 93.47 Percentage of Particiopants |
Primary
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.
Time frame: Year 4 (Weeks 168 and 192)
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed for CDP at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS | CDP Sustained for 24 weeks: At Week 168 | 85.98 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS | CDP Sustained for 48 weeks: At Week 168 | 87.98 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS | CDP Sustained for 24 weeks: At Week 192 | 84.18 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS | CDP Sustained for 48 weeks: At Week 192 | 86.48 Percentage of Participants |
Primary
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS
Time frame: Year 3
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS | Worsened (>0.5) | 9.3 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS | Stable (Change <= 0.5 and >= -0.5) | 81.5 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS | Improved (<-0.5) | 9.2 Percentage of Participants |
Primary
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS
Time frame: Year 4
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS | Worsened (>0.5) | 18.0 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS | Stable (Change <= 0.5 and >= -0.5) | 59.3 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS | Improved (<-0.5) | 22.8 Percentage of Participants |
Primary
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS
Time frame: Year 1 (Week 48)
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS | Week 48 Worsened (>0.5) | 9.3 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS | Week 48 Stable (Change <= 0.5 and >= -0.5) | 73.3 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS | Week 48 Improved (<-0.5) | 17.5 Percentage of Participants |
Primary
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS
Time frame: Year 2 (Week 96)
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS | Week 96 Worsened (>0.5) | 11.9 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS | Week 96 Stable (Change <= 0.5 and >= -0.5) | 76.6 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS | Week 96 Improved (<-0.5) | 11.6 Percentage of Participants |
Primary
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS
CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Time frame: At Weeks 144, 168 and 192 during Year 4
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed for CDP at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 144 | 100.00 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS | CDI Sustained for 48 weeks: At Week 144 | 100.00 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 168 | 99.54 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS | CDI Sustained for 48 weeks: At Week 168 | 100.00 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 192 | 93.77 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS | CDI Sustained for 48 weeks: At Week 192 | 98.01 Percentage of Participants |
Primary
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS
CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Time frame: At Weeks 48, 72 and 96 during Year 2
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 48 | 100.0 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS | CDI Sustained for 48 weeks: At Week 48 | 100.00 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 72: | 97.20 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS | CDI Sustained for 48 weeks: At Week 72 | 97.60 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 96 | 90.29 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS | CDI Sustained for 48 weeks: At Week 96 | 92.55 Percentage of Participants |
Primary
Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS
CDI is defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Time frame: At Weeks 24 and 48 during Year 1
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 24 | 95.11 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS | CDI Sustained for 24 weeks: At Week 48 | 83.50 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS | CDI Sustained for 48 weeks: At Week 48 | 87.54 Percentage of Participants |
Primary
Percentage of Participants Without Protocol-Defined Event of Disease Activity
Protocol-defined event of disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis \[MS\], as determined using EDSS/Functional Systems Score \[FSS\] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8 (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.
Time frame: Baseline up to 4 years
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 24 | 95.98 Percentage of participants |
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 48 | 88.94 Percentage of participants |
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 72 | 83.94 Percentage of participants |
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 96 | 80.38 Percentage of participants |
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 120 | 77.38 Percentage of participants |
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 144 | 75.76 Percentage of participants |
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 168 | 72.79 Percentage of participants |
| Ocrelizumab | Percentage of Participants Without Protocol-Defined Event of Disease Activity | Week 192 | 70.67 Percentage of participants |
Primary
Percentage of Participants Without Relapse
Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
Time frame: Baseline up to 4 years
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Without Relapse | Week 24 | 98.52 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Relapse | Week 48 | 97.91 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Relapse | Week 72 | 96.25 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Relapse | Week 96 | 95.32 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Relapse | Week 120 | 93.90 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Relapse | Week 144 | 93.09 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Relapse | Week 168 | 92.43 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Relapse | Week 192 | 91.56 Percentage of Participants |
Primary
Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy
Time frame: Week 24 through Week 144
Population: ITT Population included all randomized participants in shorter infusion sub study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ocrelizumab | Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy | 101 Participants |
| Substudy - Shorter Infusion | Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy | 107 Participants |
Primary
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS)
The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits for a minimum of 24 weeks/48 weeks.
Time frame: Baseline up to 4 years
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Ocrelizumab | Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS) | CPD Sustained for at Least 24 weeks | NA weeks |
| Ocrelizumab | Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS) | CDP Sustained for at Least 48 weeks | NA weeks |
Secondary
Change From Baseline in Brain Volume as Detected by Brain MRI
Percentage change from Normalized brain volume in cm3 (cubic centimeter)values are reported
Time frame: From Baseline to Weeks 24, 48, 96, 144, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in Brain Volume as Detected by Brain MRI | Week 24 | -0.189 Percentage Change in Volume (cm3) | Standard Deviation 0.564 |
| Ocrelizumab | Change From Baseline in Brain Volume as Detected by Brain MRI | Week 48 | -0.479 Percentage Change in Volume (cm3) | Standard Deviation 0.733 |
| Ocrelizumab | Change From Baseline in Brain Volume as Detected by Brain MRI | Week 96 | -0.909 Percentage Change in Volume (cm3) | Standard Deviation 0.93 |
| Ocrelizumab | Change From Baseline in Brain Volume as Detected by Brain MRI | Week 144 | -1.283 Percentage Change in Volume (cm3) | Standard Deviation 1.156 |
| Ocrelizumab | Change From Baseline in Brain Volume as Detected by Brain MRI | Week 192 | -1.535 Percentage Change in Volume (cm3) | Standard Deviation 1.311 |
Secondary
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R)
BICAMS assesses cognitive processing speed and verbal and visual memory. BVMT-R assesses visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.
Time frame: Baseline, Weeks 48, 96, 144, 192
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) | Baseline | 23.69 points on a scale | Standard Deviation 6.44 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) | Change at Week 48 | -0.71 points on a scale | Standard Deviation 5.31 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) | Change at Week 96 | 0.82 points on a scale | Standard Deviation 5.68 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) | Change at Week 144 | 3.15 points on a scale | Standard Deviation 5.37 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R) | Change at Week 192 | 1.06 points on a scale | Standard Deviation 7.09 |
Secondary
Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II)
BICAMS assesses cognitive processing speed and verbal and visual memory. The CLVT-II is an assessment of verbal learning and memory which measures recall and recognition scores, encoding strategies, learning rates and error types. A list learning task with 16 words from 4 semantic categories are read over a series of 5 list presentations. Recall is assessed after learning and at a 20-minute delay. The maximum possible score is 80 and a minimum is 0. A higher score indicated better recall.
Time frame: Baseline, Weeks 48, 96, 144, 192
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) | Change at Week 48 | 2.02 score on a scale | Standard Deviation 8.29 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) | Change at Week 96 | 2.71 score on a scale | Standard Deviation 9.25 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) | Change at Week 144 | 3.99 score on a scale | Standard Deviation 7.6 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II) | Change at Week 192 | 4.28 score on a scale | Standard Deviation 13.76 |
Secondary
Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT)
BICAMS is assessing cognitive processing speed and verbal and visual memory. SDMT assesses processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 second time span. The higher the results, the better processing speed/working memory.
Time frame: Baseline, Weeks 48, 96, 144, 192
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Overall number analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with data available for analyses at the specified timepoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) | Change at Week 48 | 2.48 responses over 90 seconds | Standard Deviation 10.12 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) | Change at Week 96 | 1.89 responses over 90 seconds | Standard Deviation 9.98 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) | Change at Week 144 | 3.33 responses over 90 seconds | Standard Deviation 9.31 |
| Ocrelizumab | Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT) | Change at Week 192 | 4.38 responses over 90 seconds | Standard Deviation 10.38 |
Secondary
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score
The mean change in 9 Hole Peg Test (9HPT)-score is reported. Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. The number of seconds it takes to complete the test, the higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.
Time frame: Weeks 24, 48, 72, 96, 120, 144, 168, 192
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 24 | -0.47 seconds | Standard Deviation 14.44 |
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 48 | -1.22 seconds | Standard Deviation 11.54 |
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 72 | -1.78 seconds | Standard Deviation 8.09 |
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 96 | -1.67 seconds | Standard Deviation 10.91 |
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 120 | -0.87 seconds | Standard Deviation 15.21 |
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 144 | -1.91 seconds | Standard Deviation 8.7 |
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 168 | -1.84 seconds | Standard Deviation 10.68 |
| Ocrelizumab | Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score | Change at Week 192 | -0.73 seconds | Standard Deviation 17.55 |
Secondary
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score
Mean change in the Paced Auditory Serial Addition Test \[PASAT\] score is reported. PASAT measures cognitive function. A total of 60 single digit numbers are presented by an audiotape/CD-rom at a constant rate in every 3 seconds (PASAT-3). Participants are required to add each new number to the one immediately before it. Due to the relative complexity of this test, a practice trial with a set of 10 numbers should be performed before the original test. Participants are allowed up to 3 practice trials. Two sets of numbers (forms A & B) are developed to be used alternatively in every visit to minimize memorizing. The number of correct answers is recorded. The PASAT score ranges from 0 to 60, with higher values representing a better outcome in cognitive processing speed. Subsequently, higher values in mean changes from baseline over the study time indicate improvement in cognitive function.
Time frame: Weeks 24, 48, 72, 96, 120, 144, 168, 192
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 24 | 4.18 score on a scale | Standard Deviation 9.26 |
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 48 | 5.40 score on a scale | Standard Deviation 9.52 |
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 72 | 6.33 score on a scale | Standard Deviation 11.59 |
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 96 | 7.66 score on a scale | Standard Deviation 10.93 |
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 120 | 7.69 score on a scale | Standard Deviation 12.95 |
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 144 | 8.45 score on a scale | Standard Deviation 10.02 |
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 168 | 8.47 score on a scale | Standard Deviation 11.79 |
| Ocrelizumab | Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score | Change at Week 192 | 9.64 score on a scale | Standard Deviation 11.56 |
Secondary
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score.
The change in the mean score of T25FW is reported below. The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, the higher score, which indicates deterioration. Lower times indicate better performance and greater mobility. Higher times indicate worse performance and greater impairment. Subsequently, the lower the mean change in the score over time, the better performance.
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 24 | -0.31 seconds | Standard Deviation 6.62 |
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 48 | -0.49 seconds | Standard Deviation 6.88 |
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 72 | -0.56 seconds | Standard Deviation 6.99 |
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 96 | -0.62 seconds | Standard Deviation 6.95 |
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 120 | -0.44 seconds | Standard Deviation 7.94 |
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 144 | -0.97 seconds | Standard Deviation 6.25 |
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 168 | -0.83 seconds | Standard Deviation 6.64 |
| Ocrelizumab | Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score. | Change at Week 192 | 0.09 seconds | Standard Deviation 9.37 |
Secondary
Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI
Time frame: Baseline, Weeks 48, 96, 144, 192
Population: ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI | Week 48 | -310.63 Micro Liter | Standard Deviation 708.07 |
| Ocrelizumab | Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI | Week 96 | -405.61 Micro Liter | Standard Deviation 755.99 |
| Ocrelizumab | Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI | Week 144 | -359.76 Micro Liter | Standard Deviation 761.84 |
| Ocrelizumab | Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI | Week 192 | -307.64 Micro Liter | Standard Deviation 797.87 |
Secondary
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score
WPAI scale measures impact of health problems on work productivity and regular activities: Absenteeism (Work Time Missed) measuring % of work time missed due to health issues; Presenteeism:Calculated as the percentage of impairment while working due to health problems. Overall Work Impairment:Calculated by combining absenteeism and presenteeism using the formula:Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism This formula accounts for both the time missed and the reduced productivity while at work. Activity Impairment: Calculated as the percentage of impairment in regular activities outside of work. Range: Each component is scored as 0%-100%). Higher % indicate greater impairment and worse outcomes.
Time frame: Baseline, Weeks 24, 48, 96, 120, 144, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Work productivity Baseline | 26.33 WAPI Sub-Score | Standard Deviation 31.84 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Work productivity Week 24 | 17.65 WAPI Sub-Score | Standard Deviation 25.04 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Work productivity Week 48 | 18.83 WAPI Sub-Score | Standard Deviation 25.92 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Work productivity Week 96 | 16.46 WAPI Sub-Score | Standard Deviation 23.1 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Work productivity Week 144 | 16.78 WAPI Sub-Score | Standard Deviation 23.85 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Work productivity Week 192 | 15.80 WAPI Sub-Score | Standard Deviation 22.25 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Activity Impairment Baseline | 23.23 WAPI Sub-Score | Standard Deviation 24.79 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Activity Impairment Week 24 | 18.09 WAPI Sub-Score | Standard Deviation 22.15 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Presenteeism Week 48 | 18.85 WAPI Sub-Score | Standard Deviation 23.37 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Activity Impairment Week 96 | 17.79 WAPI Sub-Score | Standard Deviation 22.92 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Activity Impairment Week 144 | 17.80 WAPI Sub-Score | Standard Deviation 23.74 |
| Ocrelizumab | Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score | Activity Impairment Week 192 | 18.18 WAPI Sub-Score | Standard Deviation 23.25 |
Secondary
Percentage of Participants Who Are Relapse Free
Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
Time frame: Week 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Overall number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Percentage of Participants Who Are Relapse Free | 92.00 Percentage of Participants |
Secondary
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to 4 years
Population: Safety and ITT populations
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse Events | 95.8 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious Adverse Events | 15.0 Percentage of Participants |
Secondary
Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD)
NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion. CDP will be assessed using EDSS. Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
Time frame: Weeks 96, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) | Week 96 | 70.29 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) | Week 192 | 58.89 Percentage of Participants |
Secondary
Percentage of Participants With No Evidence of Protocol Defined Disease Activity
Protocol-defined disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis \[MS\], as determined using EDSS/Functional Systems Score \[FSS\] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8. (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan. Event-free rate
Time frame: Weeks 96, 144, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants With No Evidence of Protocol Defined Disease Activity | Week 96 | 80.38 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With No Evidence of Protocol Defined Disease Activity | Week 144 | 75.76 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With No Evidence of Protocol Defined Disease Activity | Week 192 | 70.67 Percentage of Participants |
Secondary
Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP)
NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20 percent \[%\] increase from baseline in timed 25 Foot Walk Test \[T25FWT\]; 20% increase from baseline in timed 9 hole peg test \[9HPT\]). CDP will be assessed using EDSS.
Time frame: Weeks 96, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP) | Week 96 | 79.60 Percentage of Participants |
| Ocrelizumab | Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP) | Week 192 | 69.16 Percentage of Participants |
Secondary
Percentage of Participants Without Treatment Discontinuation
Time frame: Baseline up to 4 years
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 48 | 97.49 Percentage % |
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 24 | 98.97 Percentage % |
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 72 | 96.02 Percentage % |
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 96 | 93.51 Percentage % |
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 120 | 92.04 Percentage % |
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 144 | 89.23 Percentage % |
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 168 | 87.17 Percentage % |
| Ocrelizumab | Percentage of Participants Without Treatment Discontinuation | Week 192 | 83.85 Percentage % |
Secondary
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score
The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a questionnaire to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective, which includes 29 items self-reported measures associated with a physical scale and 9 items with a psychological scale. MSIS-29 scales are generated by summing items and it's ranging from 29-145'. The higher total MSIS-29 scores indicate a greater degree of disability. The mean change in MSIS-29 scores from baseline is reported. The decreasing values in the mean change from baseline indicate functional improvement from patients' perspective
Time frame: Baseline, Weeks 24, 48, 96, 144, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score | Week 24 | -2.43 Change in MSIS-29 Mean Score | Standard Deviation 12.13 |
| Ocrelizumab | Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score | Week 48 | -2.15 Change in MSIS-29 Mean Score | Standard Deviation 13.04 |
| Ocrelizumab | Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score | Week 96 | -1.26 Change in MSIS-29 Mean Score | Standard Deviation 14.31 |
| Ocrelizumab | Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score | Week 144 | -0.73 Change in MSIS-29 Mean Score | Standard Deviation 14.83 |
| Ocrelizumab | Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score | Week 192 | -0.63 Change in MSIS-29 Mean Score | Standard Deviation 16.04 |
Secondary
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total
MSFC combines the following: Timed 25 Foot Walk Test \[T25FWT\] for leg function &ambulation measured in seconds (sec). The longer it takes to walk, higher the score indicating deterioration; 9 Hole Peg Test \[9HPT\] for arm & handf unction measured in sec. Higher score=more time taken to complete test indicating deterioration. Paced Auditory Serial Addition Test \[PASAT\] for cognitive function (score range: 0-60, higher score=better cognitive processing speed). MSFC composite={\[Average(1/9-HPT)-Baseline Mean(1/9-HPT)/Baseline Std Dev(1/9-HPT)\]+\[-(Average T25FWT-Baseline Mean T25FWT)/Baseline Std-Dev T25FWT\]+\[(PASAT-3-BaselineMean PASAT-3)/Baseline Std Dev PASAT-3\]}/ 3.0. MSFC is based on the concept that scores for these 3 dimensions are combined to create a single score to detect change over time in a group of MS patients. Higher composite score=better overall function. Lower score=worse overall function. Higher mean change in total MSFC score=functional improvement at cohort level.
Time frame: Weeks 24, 48, 72, 96, 120, 144, 168, 192
Population: Treatment efficacy was measured for this First Enrollment Cohort ITT population. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at the specified timepoint. Different participants may have contributed data for each timepoint. As raw composite scores have been reported here, it is not possible to provide a score range for this scale.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 24 | 0.09 score on a scale | Standard Deviation 0.67 |
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 48 | 0.11 score on a scale | Standard Deviation 0.54 |
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 72 | 0.12 score on a scale | Standard Deviation 0.45 |
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 96 | 0.14 score on a scale | Standard Deviation 0.53 |
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 120 | 0.16 score on a scale | Standard Deviation 0.61 |
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 144 | 0.16 score on a scale | Standard Deviation 0.48 |
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 168 | 0.18 score on a scale | Standard Deviation 0.56 |
| Ocrelizumab | Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total | Change at Week 192 | 0.19 score on a scale | Standard Deviation 0.72 |
Secondary
Substudy: IRRs Leading to Treatment Discontinuation
Time frame: From Week 24 to Week 144
Population: ITT Population included all randomized participants in shorter infusion sub study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Substudy: IRRs Leading to Treatment Discontinuation | 0 symptoms |
| Substudy - Shorter Infusion | Substudy: IRRs Leading to Treatment Discontinuation | 0 symptoms |
Secondary
Substudy: Number of IRR Symptoms
Time frame: From Week 24 to Week 144
Population: ITT Population included all randomized participants in shorter infusion sub study. Overall number of participants analyzed is the number of participants with data available for analyses. Number analyzed is the number of participants with an infusion.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Substudy: Number of IRR Symptoms | 471 symptoms |
| Substudy - Shorter Infusion | Substudy: Number of IRR Symptoms | 458 symptoms |
Secondary
Substudy: Number of Participants With IRR Overall and by Dose at Randomization
Time frame: From Week 24 to Week 144
Population: ITT Population included all randomized participants in shorter infusion sub study. Number analyzed is the number of participants who received an infusion.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ocrelizumab | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 2nd Randomized Dose | 84 Participants |
| Ocrelizumab | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 4th Randomized Dose | 14 Participants |
| Ocrelizumab | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 1st Randomized Dose | 101 Participants |
| Ocrelizumab | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 5th Randomized Dose | 1 Participants |
| Ocrelizumab | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 3rd Randomized Dose | 62 Participants |
| Ocrelizumab | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 6th Randomized Dose | 0 Participants |
| Ocrelizumab | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | All Randomized Doses (Overall) | 155 Participants |
| Substudy - Shorter Infusion | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 6th Randomized Dose | 0 Participants |
| Substudy - Shorter Infusion | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | All Randomized Doses (Overall) | 172 Participants |
| Substudy - Shorter Infusion | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 1st Randomized Dose | 107 Participants |
| Substudy - Shorter Infusion | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 2nd Randomized Dose | 96 Participants |
| Substudy - Shorter Infusion | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 3rd Randomized Dose | 82 Participants |
| Substudy - Shorter Infusion | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 4th Randomized Dose | 17 Participants |
| Substudy - Shorter Infusion | Substudy: Number of Participants With IRR Overall and by Dose at Randomization | 5th Randomized Dose | 3 Participants |
Secondary
Substudy: Severity of IRRs
The number of participants with IRRs by most extreme intensity were reported (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 =life-threatening, grade 5 = fatal). Multiple IRRs in one participant are counted only once at the most extreme (highest) intensity observed.
Time frame: From Week 24 to Week 144
Population: ITT Population included all randomized participants in shorter infusion sub study. Number analyzed is the number of participants with IRR.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ocrelizumab | Substudy: Severity of IRRs | Grade 4 (Life-Threatening) | 0 Participants |
| Ocrelizumab | Substudy: Severity of IRRs | Grade 1 (Mild) | 88 Participants |
| Ocrelizumab | Substudy: Severity of IRRs | Grade 2 (Moderate) | 66 Participants |
| Ocrelizumab | Substudy: Severity of IRRs | Grade 3 (Severe) | 1 Participants |
| Ocrelizumab | Substudy: Severity of IRRs | Grade 5 (Fatal) | 0 Participants |
| Substudy - Shorter Infusion | Substudy: Severity of IRRs | Grade 5 (Fatal) | 0 Participants |
| Substudy - Shorter Infusion | Substudy: Severity of IRRs | Grade 3 (Severe) | 4 Participants |
| Substudy - Shorter Infusion | Substudy: Severity of IRRs | Grade 1 (Mild) | 92 Participants |
| Substudy - Shorter Infusion | Substudy: Severity of IRRs | Grade 4 (Life-Threatening) | 0 Participants |
| Substudy - Shorter Infusion | Substudy: Severity of IRRs | Grade 2 (Moderate) | 76 Participants |
Secondary
SymptoMScreen Composite Score
The SMSS consists of 12 items which are assessed on a seven-point Likert scale that ranges from 0 (not at all affected) to 6 (total limitation) \[7\]. The total score ranges from 0 to 72, with higher scores indicating more severe symptom endorsement.
Time frame: Baseline, Weeks 24, 48, 96, 144, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort. Number analyzed per timepoint are unique number of participants out of all the participants who were assessed at that timepoint. Different participants may have contributed data for each timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | SymptoMScreen Composite Score | Week 24 | -0.1 Change in SymptoMScreen Composite Score | Standard Deviation 0.9 |
| Ocrelizumab | SymptoMScreen Composite Score | Week 48 | -0.1 Change in SymptoMScreen Composite Score | Standard Deviation 1 |
| Ocrelizumab | SymptoMScreen Composite Score | Week 96 | 0.0 Change in SymptoMScreen Composite Score | Standard Deviation 1.1 |
| Ocrelizumab | SymptoMScreen Composite Score | Week 144 | 0.0 Change in SymptoMScreen Composite Score | Standard Deviation 1.1 |
| Ocrelizumab | SymptoMScreen Composite Score | Week 192 | 0.0 Change in SymptoMScreen Composite Score | Standard Deviation 1.1 |
Secondary
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI
Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI was measured for its volumes.
Time frame: Baseline, Weeks 8, 24, 48, 96, 144, 192
Population: First Enrollment Cohort ITT population. Treatment efficacy was measured for this First Enrollment Cohort.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Baseline Week 8 0 | 633 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Baseline Week 8 1 | 6 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 24 0 | 635 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 24 1 | 6 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 48 0 | 631 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 48 1 | 6 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 96 0 | 611 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 96 1 | 7 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 144 0 | 550 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 144 1 | 5 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 192 0 | 530 Number of Lesions |
| Ocrelizumab | Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI | Week 192 1 | 5 Number of Lesions |
Secondary
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI
Number of Lesions are categorized as followed: 1, 2, 3, \>1
Time frame: Baseline, Weeks 24, 48, 96, 144, 192
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 144 Number of Lesions 3 | 1 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 144 Number of Lesions >1 | 2 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 24 Number of Lesions 2 | 3 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 24 Number of Lesions 0 | 651 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 24 Number of Lesions 1 | 13 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 24 Number of Lesions >1 | 3 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 48 Number of Lesions 0 | 644 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 48 Number of Lesions 1 | 11 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 48 Number of Lesions 2 | 3 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 48 Number of Lesions 3 | 2 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 48 Number of Lesions >1 | 5 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 96 Number of Lesions 0 | 624 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 96 Number of Lesions 1 | 8 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 96 Number of Lesions 2 | 1 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 96 Number of Lesions >1 | 1 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 144 Number of Lesions 0 | 564 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 144 Number of Lesions 1 | 6 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 144 Number of Lesions 2 | 1 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 192 Number of Lesions 0 | 546 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 192 Number of Lesions 1 | 4 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 192 Number of Lesions 2 | 1 Number of Lesions |
| Ocrelizumab | Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI | Week 192 Number of Lesions >1 | 1 Number of Lesions |
Secondary
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI
Number of Lesions are categorized as followed: 1, 2, 3, \>1, \>3
Time frame: Weeks 24, 48, 96, 144, 192
Population: ITT population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 24 Number of Lesions 0 | 659 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 24 Number of Lesions 1 | 6 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 24 Number of Lesions 2 | 2 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 24 Number of Lesions >1 | 2 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 48 Number of Lesions 0 | 650 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 48 Number of Lesions 1 | 7 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 96 Number of Lesions 0 | 629 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 96 Number of Lesions 1 | 1 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 144 Number of Lesions 0 | 567 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 144 Number of Lesions 1 | 1 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 144 Number of Lesions 3 | 1 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 144 Number of Lesions >1 | 1 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 192 Number of Lesions 0 | 545 Number of Lesions |
| Ocrelizumab | Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI | Week 192 Number of Lesions 1 | 1 Number of Lesions |