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    Clinical Trial Results:
    AN OPEN-LABEL, SINGLE-ARM STUDY TO EVALUATE THE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB IN PATIENTS WITH EARLY STAGE RELAPSING REMITTING MULTIPLE SCLEROSIS

    Summary
    EudraCT number
    		 2016-002937-31
    Trial protocol
    		 NO   SE   AT   DK   DE   PT   BE   HU   PL   SK   ES   BG   SI   NL   GB   FR   HR   IT  
    Global end of trial date
    27 Apr 2023

    Results information
    Results version number
    		 v1
    This version publication date
    12 May 2024
    First version publication date
    12 May 2024
    Other versions
    		 v2

    Trial information

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    Trial identification
    Sponsor protocol code
    MA30143
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, 4058
    Public contact
    Roche Trial Information Hotline, Hoffmann-La Roche, +41 61 6878333,
    Scientific contact
    Medical Communications, Hoffmann-La Roche, +1 8008218590, genentech@druginfo.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Apr 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    27 Apr 2023
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Apr 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    TO EVALUATE THE EFFECTIVENESS AND SAFETY OF OCRELIZUMAB IN PATIENTS WITH EARLY STAGE RELAPSING REMITTING MULTIPLE SCLEROSIS
    Protection of trial subjects
    The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP) guidelines according to the regulations and procedures described in the protocol.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 14
    Country: Number of subjects enrolled
    Australia: 55
    Country: Number of subjects enrolled
    Austria: 11
    Country: Number of subjects enrolled
    Belgium: 39
    Country: Number of subjects enrolled
    Bulgaria: 28
    Country: Number of subjects enrolled
    Brazil: 21
    Country: Number of subjects enrolled
    Canada: 67
    Country: Number of subjects enrolled
    Switzerland: 21
    Country: Number of subjects enrolled
    Germany: 78
    Country: Number of subjects enrolled
    Denmark: 11
    Country: Number of subjects enrolled
    Spain: 36
    Country: Number of subjects enrolled
    France: 69
    Country: Number of subjects enrolled
    United Kingdom: 52
    Country: Number of subjects enrolled
    Croatia: 36
    Country: Number of subjects enrolled
    Hungary: 15
    Country: Number of subjects enrolled
    Italy: 60
    Country: Number of subjects enrolled
    Kuwait: 5
    Country: Number of subjects enrolled
    Lebanon: 6
    Country: Number of subjects enrolled
    Mexico: 72
    Country: Number of subjects enrolled
    Netherlands: 24
    Country: Number of subjects enrolled
    Norway: 6
    Country: Number of subjects enrolled
    Poland: 153
    Country: Number of subjects enrolled
    Portugal: 27
    Country: Number of subjects enrolled
    Romania: 19
    Country: Number of subjects enrolled
    Slovakia: 28
    Country: Number of subjects enrolled
    Slovenia: 12
    Country: Number of subjects enrolled
    Sweden: 10
    Country: Number of subjects enrolled
    Türkiye: 47
    Country: Number of subjects enrolled
    United States: 203
    Worldwide total number of subjects
    1225
    EEA total number of subjects
    662
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    1225
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Full cohort includes both 1st Enrollment Cohort in the ''original'' study and 2nd Enrollment Cohort to participate in the shorter infusion substudy.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Ocrelizumab
    Arm description
    		 First Enrollment Cohort. 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
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    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)

    Number of subjects in period 1
    		Ocrelizumab
    Started
    1225
    Treatment Period
    1225
    Safety Follow-up Period
    59 [1]
    Completed
    1010
    Not completed
    215
         Adverse event, serious fatal
    12
         Site Closure
    3
         Physician decision
    13
         planned pregnancy
    17
         Consent withdrawn by subject
    77
         Changed to Commercial Ocrelizumab
    4
         Adverse event, non-fatal
    25
         Pregnancy
    7
         Terminated By Sponsor
    14
         Lost to follow-up
    17
         disease progression
    1
         Protocol deviation
    15
         Lack of efficacy
    10
    Notes
    [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ocrelizumab
    Reporting group description
    		 First Enrollment Cohort. 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

    Reporting group values
    		 Ocrelizumab Total
    Number of subjects
    		 1225 1225
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 0 0
        From 65-84 years
    		 1225 1225
        85 years and over
    		 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 32.7 ( 9.1 ) -
    Sex: Female, Male
    Units:
        Female
    		 784 784
        Male
    		 441 441
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 11 11
        Asian
    		 19 19
        Native Hawaiian or Other Pacific Islander
    		 2 2
        Black or African American
    		 34 34
        White
    		 1007 1007
        More than one race
    		 37 37
        Unknown or Not Reported
    		 115 115
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 145 145
        Not Hispanic or Latino
    		 960 960
        Unknown or Not Reported
    		 120 120

    End points

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    End points reporting groups
    Reporting group title
    Ocrelizumab
    Reporting group description
    		 First Enrollment Cohort. 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

    Primary: Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS)

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    End point title
    		 Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS) [1]
    End point description
    The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
    End point type
    Primary
    End point timeframe
    Baseline up to 4 years
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Event-free Rate Estimate %
    median (confidence interval 95%)
        Sustained 24 Wks Event-free estimate 24 Wks
    99.55 (98.62 to 99.86)
        Sustained 24 Wks Event-free estimate 48 Wks
    97.3 (95.75 to 98.29)
        Sustained 24 Wks Event-free estimate 72 Wks
    93.97 (91.87 to 95.54)
        Sustained 24 Wks Event-free estimate 96 Wks
    91.65 (89.26 to 93.52)
        Sustained 24 Wks Event-free estimate 120 Wks
    90.07 (87.51 to 92.13)
        Sustained 24 Wks Event-free estimate 144 Wks
    88.61 (85.91 to 90.83)
        Sustained 24 Wks Event-free estimate 168 Wks
    85.98 (83.04 to 88.44)
        Sustained 24 Wks Event-free estimate 192 Wks
    84.18 (81.08 to 86.81)
        Sustained 48 Wks Event-free estimate Wk 24
    99.55 (98.62 to 99.86)
        Sustained 48 Wks Event-free estimate Wk 48
    98.05 (96.67 to 98.87)
        Sustained 48 Wks Event-free estimate Wk 72
    95.18 (93.25 to 96.56)
        Sustained 48 Wks Event-free estimate Wk 96
    93.47 (91.30 to 95.12)
        Sustained 48 Wks Event-free estimate Wk 120
    91.73 (89.34 to 93.61)
        Sustained 48 Wks Event-free estimate Wk 144
    90.12 (87.55 to 92.18)
        Sustained 48 Wks Event-free estimate Wk 168
    87.98 (85.20 to 90.27)
        Sustained 48 Wks Event-free estimate Wk 192
    86.48 (83.54 to 88.93)
    No statistical analyses for this end point

    Primary: Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 1, As Measured Using EDSS

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    End point title
    		 Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 1, As Measured Using EDSS [2]
    End point description
    This Outcome Measure is reported in the Outcome Measure 1: Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS)
    End point type
    Primary
    End point timeframe
    Year 1
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    0 [3]
    Units: Percentage of Participants
        median (confidence interval 95%)
    ( to )
    Notes
    [3] - No data
    No statistical analyses for this end point

    Primary: Percentage of Participants With CDI at Year 4, As Measured Using EDSS

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    End point title
    		 Percentage of Participants With CDI at Year 4, As Measured Using EDSS [4]
    End point description
    End point type
    Primary
    End point timeframe
    Year 4
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Percentage of Participants
    median (confidence interval 95%)
        Week 144
    100.00 (100.00 to 100.00)
        Week 168
    99.54 (96.77 to 99.93)
        Week 192
    93.77 (89.51 to 96.34)
    No statistical analyses for this end point

    Primary: Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 4, As Measured Using EDSS

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    End point title
    		 Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 4, As Measured Using EDSS [5]
    End point description
    This Outcome Measure is reported in the Outcome Measure 1: Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS)
    End point type
    Primary
    End point timeframe
    Year 4
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    0 [6]
    Units: Percentage of Participants
        median (confidence interval 95%)
    ( to )
    Notes
    [6] - No data
    No statistical analyses for this end point

    Primary: Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS

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    End point title
    		 Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS [7]
    End point description
    End point type
    Primary
    End point timeframe
    Year 1 (Week 48)
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Percentage of Participants
    number (not applicable)
        Week 48 Worsened (>0.5)
    9.3
        Week 48 Stable (Change <= 0.5 and >= -0.5)
    73.3
        Week 48 Improved (<-0.5)
    17.5
    No statistical analyses for this end point

    Primary: Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 2, As Measured Using EDSS

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    End point title
    		 Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 2, As Measured Using EDSS [8]
    End point description
    This Outcome Measure is reported in the Outcome Measure 1: Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS)
    End point type
    Primary
    End point timeframe
    Year 2
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    0 [9]
    Units: Percentage of Particiopants
        median (confidence interval 95%)
    ( to )
    Notes
    [9] - No data
    No statistical analyses for this end point

    Primary: Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS

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    End point title
    		 Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS [10]
    End point description
    End point type
    Primary
    End point timeframe
    Year 2 (Week 96)
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Percentage of Participants
    number (not applicable)
        Week 96 Worsened (>0.5)
    11.9
        Week 96 Stable (Change <= 0.5 and >= -0.5)
    76.6
        Week 96 Improved (<-0.5)
    11.6
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 24

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 24 [11]
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline to Week 24
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    671
    Units: Change in Total EDSS
        arithmetic mean (standard deviation)
    -0.14 ( 0.68 )
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 48

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 48 [12]
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline to Week 48
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    659
    Units: Change in Total EDSS
        arithmetic mean (standard deviation)
    -0.14 ( 0.77 )
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 192

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 192 [13]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline, Week 192
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    562
    Units: Change in Total EDSS
        arithmetic mean (standard deviation)
    -0.06 ( 1.06 )
    No statistical analyses for this end point

    Primary: Time to First Protocol-Defined Event of Disease Activity

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    End point title
    		 Time to First Protocol-Defined Event of Disease Activity [14]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Baseline up to 4 years
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Event-free Rate Estimate %
    median (confidence interval 95%)
        Week 24
    95.98 (94.20 to 97.23)
        Week 48
    88.94 (86.30 to 91.09)
        Week 72
    83.94 (80.92 to 86.52)
        Week 96
    80.38 (77.14 to 83.21)
        Week 120
    77.38 (73.99 to 80.39)
        Week 144
    75.76 (72.28 to 78.86)
        Week 168
    72.79 (69.18 to 76.05)
        Week 192
    70.67 (66.97 to 74.04)
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 168

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 168 [15]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline, Week 168
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    560
    Units: Change in Total EDSS
        arithmetic mean (standard error)
    -0.05 ( 1.05 )
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 144

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 144 [16]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline, Week 144
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    561
    Units: Change in Total EDSS
        arithmetic mean (standard error)
    -0.10 ( 1.00 )
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 96

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 96 [17]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline, Week 96
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    637
    Units: Change in Total EDSS
        arithmetic mean (standard error)
    -0.12 ( 0.95 )
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 120

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 120 [18]
    End point description
    End point type
    Primary
    End point timeframe
    Baseline, Week 120
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    579
    Units: Change in Total EDSS
        arithmetic mean (standard deviation)
    -0.10 ( 0.94 )
    No statistical analyses for this end point

    Primary: Mean Change From Baseline in EDSS Score at Week 72

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    End point title
    		 Mean Change From Baseline in EDSS Score at Week 72 [19]
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline to Week 72
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    651
    Units: Change in Total EDSS
        arithmetic mean (standard deviation)
    -0.09 ( 0.89 )
    No statistical analyses for this end point

    Primary: Time to First Relapse

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    End point title
    		 Time to First Relapse [20]
    End point description
    Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
    End point type
    Primary
    End point timeframe
    Baseline up to 4 years
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Event free Rate Estimate %
    median (confidence interval 95%)
        Week 24
    98.52 (97.26 to 99.20)
        Week 48
    97.91 (96.50 to 98.76)
        Week 72
    96.25 (94.49 to 97.45)
        Week 96
    95.32 (93.41 to 96.69)
        Week 120
    93.90 (91.78 to 95.49)
        Week 144
    93.09 (90.85 to 94.79)
        Week 168
    92.43 (90.10 to 94.23)
        Week 192
    91.56 (89.12 to 93.48)
    No statistical analyses for this end point

    Primary: Annualized Relapse Rate

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    End point title
    		 Annualized Relapse Rate [21]
    End point description
    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.
    End point type
    Primary
    End point timeframe
    Baseline up to 4 years
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Annualized Relapse Rate %
        least squares mean (confidence interval 95%)
    0.02 (0.015 to 0.027)
    No statistical analyses for this end point

    Primary: Proportion of Participants with Infusion Related Reactions (IRRs) Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy

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    End point title
    		 Proportion of Participants with Infusion Related Reactions (IRRs) Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy [22]
    End point description
    End point type
    Primary
    End point timeframe
    From Week 24 through Week 192
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    1225
    Units: Participants
    677
    No statistical analyses for this end point

    Primary: Time to onset of 24 weeks Confirmed Disability Improvement (CDI) during the Year 1 treatment period

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    End point title
    		 Time to onset of 24 weeks Confirmed Disability Improvement (CDI) during the Year 1 treatment period [23]
    End point description
    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 patients with a baseline EDSS of ≥2.0).
    End point type
    Primary
    End point timeframe
    Year 1
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    309
    Units: Percentage %
    median (confidence interval 95%)
        Event-free rate estimate (%) 24 Weeks
    95.11 (92.03 to 97.03)
        Event-free rate estimate (%) 48 Weeks
    83.50 (78.81 to 87.24)
    No statistical analyses for this end point

    Primary: Time to onset of 24 weeks Confirmed Disability Improvement (CDI) during the Year 2 treatment period

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    End point title
    		 Time to onset of 24 weeks Confirmed Disability Improvement (CDI) during the Year 2 treatment period [24]
    End point description
    End point type
    Primary
    End point timeframe
    Year 2
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    252
    Units: Percentage %
    median (confidence interval 95%)
        Event-free rate Estimate % Week 48
    100.0 (100.00 to 100.00)
        Event-free rate Estimate % Week 72
    97.20 (94.22 to 98.66)
        Event-free rate Estimate % Week 96
    90.29 (85.71 to 93.46)
    No statistical analyses for this end point

    Primary: Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS

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    End point title
    		 Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS [25]
    End point description
    End point type
    Primary
    End point timeframe
    Year 3
    Notes
    [25] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Percentage of Participants
    number (not applicable)
        Worsened (>0.5)
    9.3
        Stable (Change <= 0.5 and >= -0.5)
    81.5
        Improved (<-0.5)
    9.2
    No statistical analyses for this end point

    Primary: Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS

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    End point title
    		 Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS [26]
    End point description
    End point type
    Primary
    End point timeframe
    Year 4
    Notes
    [26] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data is being provided for each stage of this study rather than all arms in the baseline period at once
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Percentage of Participants
    number (not applicable)
        Worsened (>0.5)
    18.0
        Stable (Change <= 0.5 and >= -0.5)
    59.3
        Improved (<-0.5)
    22.8
    No statistical analyses for this end point

    Secondary: Percentage of Participants With No Evidence of Protocol Defined Disease Activity

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    End point title
    		 Percentage of Participants With No Evidence of Protocol Defined Disease Activity
    End point description
    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
    End point type
    Secondary
    End point timeframe
    Weeks 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: event free rate estimate
    median (confidence interval 95%)
        Week 96
    80.38 (77.14 to 83.21)
        Week 144
    75.76 (72.28 to 78.86)
        Week 192
    70.67 (66.97 to 74.04)
    No statistical analyses for this end point

    Secondary: Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD)

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    End point title
    		 Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD)
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Weeks 96, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: event free rate estimate
    median (confidence interval 95%)
        Week 96
    70.29 (66.65 to 73.62)
        Week 192
    58.89 (54.96 to 62.60)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Are Relapse Free

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    End point title
    		 Percentage of Participants Who Are Relapse Free
    End point description
    Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
    End point type
    Secondary
    End point timeframe
    Week 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    624
    Units: Percentage of Participants
        median (confidence interval 95%)
    92.00 (89.7 to 94.0)
    No statistical analyses for this end point

    Secondary: Change from Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score.

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    End point title
    		 Change from Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score.
    End point description
    T25FW-Composite Timed 25 Foot Walk Test (T25FW) Scores reported below. Higher scores indicate more severity.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in T25FW Score
    arithmetic mean (standard deviation)
        Week 24
    -0.31 ( 6.62 )
        Week 48
    -0.49 ( 6.88 )
        Week 72
    -0.56 ( 6.99 )
        Week 96
    -0.62 ( 6.95 )
        Week 120
    -0.44 ( 7.94 )
        Week 144
    -0.97 ( 6.25 )
        Week 168
    -0.83 ( 6.64 )
        Week 192
    0.09 ( 9.37 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score

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    End point title
    		 Change from Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score
    End point description
    Composite 9 Hole Peg Test (9HPT) Scores are reported, higher score values indicate more severity.
    End point type
    Secondary
    End point timeframe
    Weeks 24, 48, 72, 96, 120, 144, 168, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in 9HPT Score
    arithmetic mean (standard deviation)
        Week 24
    -0.47 ( 14.44 )
        Week 48
    -1.22 ( 11.54 )
        Week 72
    -1.78 ( 8.09 )
        Week 96
    -1.67 ( 10.91 )
        Week 120
    -0.87 ( 15.21 )
        Week 144
    -1.91 ( 8.70 )
        Week 168
    -1.84 ( 10.68 )
        Week 192
    -0.73 ( 17.55 )
    No statistical analyses for this end point

    Secondary: Change from Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score

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    End point title
    		 Change from Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score
    End point description
    Paced Auditory Serial Addition Test [PASAT] total scores are reported. The higher scores indicate more severity.
    End point type
    Secondary
    End point timeframe
    Weeks 24, 48, 72, 96, 120, 144, 168, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in PASAT Total Score
    arithmetic mean (standard deviation)
        Week 24
    4.18 ( 9.26 )
        Week 48
    5.40 ( 9.52 )
        Week 72
    6.33 ( 11.59 )
        Week 96
    7.66 ( 10.93 )
        Week 120
    7.69 ( 12.95 )
        Week 144
    8.45 ( 10.02 )
        Week 168
    8.47 ( 11.79 )
        Week 192
    9.64 ( 11.56 )
    No statistical analyses for this end point

    Secondary: Change from baseline in cognitive performance as measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)

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    End point title
    		 Change from baseline in cognitive performance as measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
    End point description
    Cognitive status of the participants are evaluated using BICAMS.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in BICAMS Score
    arithmetic mean (standard deviation)
        Week 48
    2.48 ( 10.12 )
        Week 96
    1.89 ( 9.98 )
        Week 144
    3.33 ( 9.31 )
        Week 192
    4.38 ( 10.38 )
    No statistical analyses for this end point

    Secondary: Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI

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    End point title
    		 Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI
    End point description
    Number of Lesions are categorized as followed: 1, 2, 3, >1, >3
    End point type
    Secondary
    End point timeframe
    Weeks 24, 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Number of Lesions
        Week 24 Number of Lesions 0
    659
        Week 24 Number of Lesions 1
    6
        Week 24 Number of Lesions 2
    2
        Week 24 Number of Lesions >1
    2
        Week 48 Number of Lesions 0
    650
        Week 48 Number of Lesions 1
    7
        Week 96 Number of Lesions 0
    629
        Week 96 Number of Lesions 1
    1
        Week 144 Number of Lesions 0
    567
        Week 144 Number of Lesions 1
    1
        Week 144 Number of Lesions 3
    1
        Week 144 Number of Lesions >1
    1
        Week 192 Number of Lesions 0
    545
        Week 192 Number of Lesions 1
    1
    No statistical analyses for this end point

    Secondary: Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI

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    End point title
    		 Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI
    End point description
    Number of Lesions are categorized as followed: 1, 2, 3, >1, >3
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Number of Lesions
        Week 24 Number of Lesions 0
    651
        Week 24 Number of Lesions 1
    13
        Week 24 Number of Lesions 2
    3
        Week 24 Number of Lesions >1
    3
        Week 48 Number of Lesions 0
    644
        Week 48 Number of Lesions 1
    11
        Week 48 Number of Lesions 2
    3
        Week 48 Number of Lesions 3
    2
        Week 48 Number of Lesions >1
    5
        Week 96 Number of Lesions 0
    624
        Week 96 Number of Lesions 1
    8
        Week 96 Number of Lesions 2
    1
        Week 96 Number of Lesions >1
    1
        Week 144 Number of Lesions 0
    564
        Week 144 Number of Lesions 1
    6
        Week 144 Number of Lesions 2
    1
        Week 144 Number of Lesions 3
    1
        Week 144 Number of Lesions >1
    2
        Week 192 Number of Lesions 0
    546
        Week 192 Number of Lesions 1
    4
        Week 192 Number of Lesions 2
    1
        Week 192 Number of Lesions >1
    1
    No statistical analyses for this end point

    Secondary: Change from baseline in total T1 hypointense lesion volume as Detected by Brain MRI

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    End point title
    		 Change from baseline in total T1 hypointense lesion volume as Detected by Brain MRI
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in Volume
    arithmetic mean (standard deviation)
        Week 48
    -310.63 ( 708.07 )
        Week 96
    -405.61 ( 755.99 )
        Week 144
    -359.76 ( 761.84 )
        Week 192
    -307.64 ( 797.87 )
    No statistical analyses for this end point

    Secondary: Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI

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    End point title
    		 Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 8, 24, 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Number of Lesions
        Baseline Week 8 0
    633
        Baseline Week 8 1
    6
        Week 24 0
    635
        Week 24 1
    6
        Week 48 0
    631
        Week 48 1
    6
        Week 96 0
    611
        Week 96 1
    7
        Week 144 0
    550
        Week 144 1
    5
        Week 192 0
    530
        Week 192 1
    5
    No statistical analyses for this end point

    Secondary: Change From Baseline in Brain Volume as Detected by Brain MRI

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    End point title
    		 Change From Baseline in Brain Volume as Detected by Brain MRI
    End point description
    Percentage change from Normalized brain volume in cm3 (cubic centimeter)values are reported
    End point type
    Secondary
    End point timeframe
    From Baseline to Weeks 24, 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Percentage Change in Volume (cm3)
    arithmetic mean (standard deviation)
        Week 24
    -0.189 ( 0.564 )
        Week 48
    -0.479 ( 0.733 )
        Week 96
    -0.909 ( 0.930 )
        Week 144
    -1.283 ( 1.156 )
        Week 192
    -1.535 ( 1.311 )
    No statistical analyses for this end point

    Secondary: Time to Treatment Discontinuation

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    End point title
    		 Time to Treatment Discontinuation
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 4 years
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Event-free Rate Estimate %
    number (confidence interval 95%)
        Week 24
    98.97 (97.85 to 99.51)
        Week 48
    97.49 (96.00 to 98.45)
        Week 72
    96.02 (94.25 to 97.25)
        Week 96
    93.51 (91.38 to 95.13)
        Week 120
    92.04 (89.73 to 93.84)
        Week 144
    89.23 (86.65 to 91.34)
        Week 168
    87.17 (84.41 to 89.47)
        Week 192
    83.85 (80.85 to 86.42)
    No statistical analyses for this end point

    Secondary: Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score

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    End point title
    		 Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score
    End point description
    Work productivity and Activity Impairment Scores are reported.
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 48, 96, 120, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: WAPI Sub-Score
    arithmetic mean (standard deviation)
        Work productivity Baseline
    26.33 ( 31.84 )
        Work productivity Week 24
    17.65 ( 25.04 )
        Work productivity Week 48
    18.83 ( 25.92 )
        Work productivity Week 96
    16.46 ( 23.10 )
        Work productivity Week 144
    16.78 ( 23.85 )
        Work productivity Week 192
    15.80 ( 22.25 )
        Activity Impairment Baseline
    23.23 ( 24.79 )
        Activity Impairment Week 24
    18.09 ( 22.15 )
        Presenteeism Week 48
    18.85 ( 23.37 )
        Activity Impairment Week 96
    17.79 ( 22.92 )
        Activity Impairment Week 144
    17.80 ( 23.74 )
        Activity Impairment Week 192
    18.18 ( 23.25 )
        Presenteeism Week 144
    17.80 ( 23.74 )
        Presenteeism Week 192
    18.18 ( 23.25 )
    No statistical analyses for this end point

    Secondary: Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score

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    End point title
    		 Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in MSIS-29 Score
    arithmetic mean (standard deviation)
        Week 24
    -2.43 ( 12.13 )
        Week 48
    -2.15 ( 13.04 )
        Week 96
    -1.26 ( 14.31 )
        Week 144
    -0.73 ( 14.83 )
        Week 192
    -0.63 ( 16.04 )
    No statistical analyses for this end point

    Secondary: SymptoMScreen Composite Score

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    End point title
    		 SymptoMScreen Composite Score
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Weeks 24, 48, 96, 144, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in SymptoMScreen Composite Score
    arithmetic mean (standard deviation)
        Week 24
    -0.1 ( 0.9 )
        Week 48
    -0.1 ( 1.0 )
        Week 96
    0.0 ( 1.1 )
        Week 144
    0.0 ( 1.1 )
        Week 192
    0.0 ( 1.1 )
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline up to 4 years
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    1225
    Units: Percentage of Participants
    number (not applicable)
        Adverse Events
    95.8
        Serious Adverse Events
    15.0
    No statistical analyses for this end point

    Secondary: Proportion of Participants with IRRs Leading to Treatment Discontinuation in the Shorter Infusion Substudy. This outcome was not measured, therefore no data to report.

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    End point title
    		 Proportion of Participants with IRRs Leading to Treatment Discontinuation in the Shorter Infusion Substudy. This outcome was not measured, therefore no data to report.
    End point description
    There were no participants observed with Infusion-Related Reaction Symptoms Leading To Discontinuation of Ocrelizumab Infusion by Randomized Dose.
    End point type
    Secondary
    End point timeframe
    From Week 24 through Week 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    0 [27]
    Units: Participants
    Notes
    [27] - There were no participants observed
    No statistical analyses for this end point

    Secondary: Short term safety related to the infusion (infusion-related reactions [IRRs], during infusion and up to 24h after) the overall safety is measured continuously at clinical visits and including every 8 week telephone visits up to 48 weeks post study.

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    End point title
    		 Short term safety related to the infusion (infusion-related reactions [IRRs], during infusion and up to 24h after) the overall safety is measured continuously at clinical visits and including every 8 week telephone visits up to 48 weeks post study.
    End point description
    Infusion Related Reactions in a Short-term safety population were counted.
    End point type
    Secondary
    End point timeframe
    Up to 4 Years
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    372
    Units: Participants
        Number of Patients with an Infusion, Overall
    372
        Overall Number of Patients with an Infusion
    107
        Number of pts with AE during the infusion
    65
    No statistical analyses for this end point

    Secondary: Time to first protocol-defined event of Evidence of Progression (NEP)

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    End point title
    		 Time to first protocol-defined event of Evidence of Progression (NEP)
    End point description
    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.
    End point type
    Secondary
    End point timeframe
    Weeks 96, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Event-free rate Estimate %
    median (confidence interval 95%)
        Week 96
    79.60 (76.33 to 82.48)
        Week 192
    69.16 (65.40 to 72.60)
    No statistical analyses for this end point

    Secondary: Secondary: Change from Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total

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    End point title
    		 Secondary: Change from Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total
    End point description
    The MSFC score combines a measure of lower limb function (T25FWT), upper limb function (9HPT) and cognitive function (PASAT) and used to detect disability progression in MS. Total MSFC scores reported, higher scores indicate progression of MS.
    End point type
    Secondary
    End point timeframe
    Weeks 24, 48, 72, 96, 120, 144, 168, 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    678
    Units: Change in MSFC Score
    arithmetic mean (standard deviation)
        Week 24
    0.09 ( 0.67 )
        Week 48
    0.11 ( 0.54 )
        Week 78
    0.12 ( 0.45 )
        Week 96
    0.14 ( 0.53 )
        Week 120
    0.16 ( 0.61 )
        Week 144
    0.16 ( 0.48 )
        Week 168
    0.18 ( 0.56 )
        Week 192
    0.19 ( 0.72 )
    No statistical analyses for this end point

    Secondary: Proportion of Participants with IRR By Dose at Randomization in the Shorter Infusion Substudy.

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    End point title
    		 Proportion of Participants with IRR By Dose at Randomization in the Shorter Infusion Substudy.
    End point description
    End point type
    Secondary
    End point timeframe
    From Week 24 through Week 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    372
    Units: Percentage of Participants %
    number (not applicable)
        1st randomized dose Overall Participants with IRR
    28.80
        2nd randomized dose Overall Participant% with IRR
    27.0
        3rd randomized dose Overall Participants with IRR
    27.3
        4th randomized dose Overall Participant% with IRR
    12.50
        5th randomized dose Overall Participant% with IRR
    14.30
        6th randomized dose Overall Participant% with IRR
    0
    No statistical analyses for this end point

    Secondary: Proportion of Participants with IRR (overall) in the Shorter Infusion Substudy.

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    End point title
    		 Proportion of Participants with IRR (overall) in the Shorter Infusion Substudy.
    End point description
    End point type
    Secondary
    End point timeframe
    From Week 24 through Week 192
    End point values
    		 Ocrelizumab
    Number of subjects analysed
    372
    Units: Participants
        Number of Participants with an Infusion, Overall
    372
        Overall Number of Participants with any IRR
    172
        Overall Number of IRR Symptoms
    458
        Overall Number of Participants with Serious IRR
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 4 Years
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Ocrelizumab
    Reporting group description
    		 First Enrollment Cohort. 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

    Serious adverse events
    		 Ocrelizumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    184 / 1225 (15.02%)
         number of deaths (all causes)
    13
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    INVASIVE DUCTAL BREAST CARCINOMA
         subjects affected / exposed
    3 / 1225 (0.24%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    INTRADUCTAL PAPILLOMA OF BREAST
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RENAL CELL CARCINOMA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    BENIGN BREAST NEOPLASM
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PAPILLARY THYROID CANCER
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    NEOPLASM PROGRESSION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    UTERINE LEIOMYOMA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MALIGNANT MELANOMA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    PHLEBITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    ABORTION INDUCED
         subjects affected / exposed
    4 / 1225 (0.33%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    ABORTION SPONTANEOUS
         subjects affected / exposed
    7 / 1225 (0.57%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    ECTOPIC PREGNANCY
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HAEMORRHAGE IN PREGNANCY
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ABORTION
         subjects affected / exposed
    3 / 1225 (0.24%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    PAIN
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OEDEMA PERIPHERAL
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Reproductive system and breast disorders
    UTERINE POLYP
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    CERVICAL DYSPLASIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    VULVOVAGINAL PAIN
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ENDOMETRIOSIS
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    OVARIAN CYST
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ASTHMA
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    NASAL SEPTUM DEVIATION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    NASAL TURBINATE HYPERTROPHY
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMOTHORAX
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    SUICIDE ATTEMPT
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    ANXIETY
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    COMPLETED SUICIDE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    POST-TRAUMATIC STRESS DISORDER
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SUICIDAL IDEATION
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    SOMATIC SYMPTOM DISORDER
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MAJOR DEPRESSION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    BIPOLAR DISORDER
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DEPRESSIVE SYMPTOM
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    MENTAL STATUS CHANGES
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Investigations
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TRANSAMINASES INCREASED
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CAPILLARY PERMEABILITY INCREASED
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    LIGAMENT SPRAIN
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MULTIPLE INJURIES
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OVERDOSE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TENDON RUPTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RADIUS FRACTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    LOWER LIMB FRACTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    LIGAMENT RUPTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FIBULA FRACTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SKIN LACERATION
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    FRACTURE DISPLACEMENT
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    WRIST FRACTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ANKLE FRACTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INFUSION RELATED REACTION
         subjects affected / exposed
    6 / 1225 (0.49%)
         occurrences causally related to treatment / all
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    CONCUSSION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FEMUR FRACTURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Congenital, familial and genetic disorders
    CRI DU CHAT SYNDROME
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    PALPITATIONS
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    PERICARDITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    NEURALGIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RADICULOPATHY
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CERVICOBRACHIAL SYNDROME
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HEADACHE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MULTIPLE SCLEROSIS RELAPSE
         subjects affected / exposed
    9 / 1225 (0.73%)
         occurrences causally related to treatment / all
    0 / 9
         deaths causally related to treatment / all
    0 / 0
    SYNCOPE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SEIZURE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PRESYNCOPE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TRIGEMINAL NEURALGIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DYSTONIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MIGRAINE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TOXIC ENCEPHALOPATHY
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    VISUAL IMPAIRMENT
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    SMALL INTESTINAL PERFORATION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OESOPHAGEAL SPASM
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ANAL FISTULA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    COLITIS ULCERATIVE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INGUINAL HERNIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VOMITING
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    BILE DUCT STONE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CHOLECYSTITIS ACUTE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    ERYTHEMA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    URINARY RETENTION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Endocrine disorders
    THYROID CYST
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OSTEOARTHRITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    BACK PAIN
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    PNEUMONIA
         subjects affected / exposed
    8 / 1225 (0.65%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    GASTROENTERITIS VIRAL
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    NEUTROPENIC SEPSIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    INFLUENZA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OTITIS MEDIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    3 / 1225 (0.24%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    PNEUMOCYSTIS JIROVECII PNEUMONIA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SUBACUTE ENDOCARDITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    COVID-19
         subjects affected / exposed
    23 / 1225 (1.88%)
         occurrences causally related to treatment / all
    0 / 23
         deaths causally related to treatment / all
    0 / 0
    HEPATITIS A
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MENINGITIS VIRAL
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA MYCOPLASMAL
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    COVID-19 PNEUMONIA
         subjects affected / exposed
    17 / 1225 (1.39%)
         occurrences causally related to treatment / all
    0 / 18
         deaths causally related to treatment / all
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    4 / 1225 (0.33%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    FALLOPIAN TUBE ABSCESS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PERITONSILLAR ABSCESS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    5 / 1225 (0.41%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    GENITAL HERPES
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    5 / 1225 (0.41%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    EPIDIDYMITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TYPHOID FEVER
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MENINGITIS BACTERIAL
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VIRAL UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VAGINAL INFECTION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RENAL ABSCESS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ORCHITIS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VARICELLA
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    VIRAL INFECTION
         subjects affected / exposed
    2 / 1225 (0.16%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    PENILE ABSCESS
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    DIABETES MELLITUS INADEQUATE CONTROL
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DECREASED APPETITE
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DEHYDRATION
         subjects affected / exposed
    1 / 1225 (0.08%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ocrelizumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1110 / 1225 (90.61%)
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION
         subjects affected / exposed
    674 / 1225 (55.02%)
         occurrences all number
    1930
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    88 / 1225 (7.18%)
         occurrences all number
    102
    HYPOAESTHESIA
         subjects affected / exposed
    91 / 1225 (7.43%)
         occurrences all number
    113
    PARAESTHESIA
         subjects affected / exposed
    98 / 1225 (8.00%)
         occurrences all number
    124
    HEADACHE
         subjects affected / exposed
    295 / 1225 (24.08%)
         occurrences all number
    639
    General disorders and administration site conditions
    FATIGUE
         subjects affected / exposed
    201 / 1225 (16.41%)
         occurrences all number
    274
    PYREXIA
         subjects affected / exposed
    98 / 1225 (8.00%)
         occurrences all number
    139
    Gastrointestinal disorders
    DIARRHOEA
         subjects affected / exposed
    91 / 1225 (7.43%)
         occurrences all number
    116
    NAUSEA
         subjects affected / exposed
    87 / 1225 (7.10%)
         occurrences all number
    109
    Respiratory, thoracic and mediastinal disorders
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    113 / 1225 (9.22%)
         occurrences all number
    156
    COUGH
         subjects affected / exposed
    126 / 1225 (10.29%)
         occurrences all number
    160
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    84 / 1225 (6.86%)
         occurrences all number
    109
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    75 / 1225 (6.12%)
         occurrences all number
    88
    ANXIETY
         subjects affected / exposed
    62 / 1225 (5.06%)
         occurrences all number
    69
    INSOMNIA
         subjects affected / exposed
    81 / 1225 (6.61%)
         occurrences all number
    85
    Musculoskeletal and connective tissue disorders
    MUSCLE SPASMS
         subjects affected / exposed
    68 / 1225 (5.55%)
         occurrences all number
    76
    BACK PAIN
         subjects affected / exposed
    115 / 1225 (9.39%)
         occurrences all number
    147
    ARTHRALGIA
         subjects affected / exposed
    132 / 1225 (10.78%)
         occurrences all number
    169
    PAIN IN EXTREMITY
         subjects affected / exposed
    133 / 1225 (10.86%)
         occurrences all number
    172
    Infections and infestations
    SINUSITIS
         subjects affected / exposed
    109 / 1225 (8.90%)
         occurrences all number
    144
    COVID-19
         subjects affected / exposed
    291 / 1225 (23.76%)
         occurrences all number
    344
    URINARY TRACT INFECTION
         subjects affected / exposed
    184 / 1225 (15.02%)
         occurrences all number
    319
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    196 / 1225 (16.00%)
         occurrences all number
    301
    INFLUENZA
         subjects affected / exposed
    96 / 1225 (7.84%)
         occurrences all number
    119
    BRONCHITIS
         subjects affected / exposed
    62 / 1225 (5.06%)
         occurrences all number
    84
    PHARYNGITIS
         subjects affected / exposed
    63 / 1225 (5.14%)
         occurrences all number
    81
    ORAL HERPES
         subjects affected / exposed
    63 / 1225 (5.14%)
         occurrences all number
    142
    NASOPHARYNGITIS
         subjects affected / exposed
    320 / 1225 (26.12%)
         occurrences all number
    646

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Nov 2016
    V2
    28 Mar 2017
    V3
    27 Jul 2018
    V4
    30 Jul 2018
    V5
    30 Dec 2018
    V6
    23 Apr 2019
    V7
    28 Apr 2020
    V8
    17 Sep 2020
    V9
    23 Mar 2021
    V10

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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