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    Clinical Trial Results:
    An Open-Label, Multicenter, Biomarker Study to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Patients With Relapsing Multiple Sclerosis or Primary Progressive Multiple Sclerosis

    Summary
    EudraCT number
    		 2015-004616-37
    Trial protocol
    		 SE   DE  
    Global end of trial date
    11 Apr 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Apr 2024
    First version publication date
    26 Apr 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ML29966
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02688985
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Genentech, Inc.
    Sponsor organisation address
    1 DNA Way, Suite 258A, South San Francisco, United States, 4070
    Public contact
    Medical Communications, Genentech, Inc., 41 800 8218590, genentech@druginfo.com
    Scientific contact
    Medical Communications, Genentech, Inc., 41 800 8218590, 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
    05 Mar 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Apr 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is an open-label, multicenter, biomarker study designed to be hypothesis-generating in order to better understand the mechanism of action of ocrelizumab and B-cell biology in RMS or PPMS.
    Protection of trial subjects
    This study was conducted in full conformance with the ICH E6 guideline for Good Clinical Practice and the principles of the Declaration of Helsinki, or the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual. All participants were required to read and sign an informed consent form prior to participation in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    29 Apr 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 34
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Sweden: 7
    Country: Number of subjects enrolled
    United States: 81
    Worldwide total number of subjects
    131
    EEA total number of subjects
    16
    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)
    131
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 131 patients enrolled at 17 study locations in the U.S., Canada, Germany, and Sweden

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 RMS Cohort Arm 1: Ocrelizumab + LP
    Arm description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 12. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    RO4964913
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ocrelizumab will be administered as IV infusion.

    Investigational medicinal product name
    Antihistamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion.

    Investigational medicinal product name
    Methyloprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion.

    Arm title
    		 RMS Cohort Arm 2: Ocrelizumab + LP
    Arm description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 24. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    RO4964913
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ocrelizumab will be administered as IV infusion.

    Investigational medicinal product name
    Antihistamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion.

    Investigational medicinal product name
    Methyloprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion.

    Arm title
    		 RMS Cohort Arm 3: Ocrelizumab + LP
    Arm description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    RO4964913
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ocrelizumab will be administered as IV infusion.

    Investigational medicinal product name
    Methyloprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion.

    Investigational medicinal product name
    Antihistamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion.

    Arm title
    		 RMS Cohort Arm 4: Ocrelizumab + LP
    Arm description
    		 Ocrelizumab treatment will be delayed for 12 weeks from pre-treatment baseline. Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP at Week -12 (pre-treatment baseline) and a second LP before the start of dosing (Week 1, treatment baseline). Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    RO4964913
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ocrelizumab will be administered as IV infusion.

    Investigational medicinal product name
    Antihistamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion.

    Investigational medicinal product name
    Methyloprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion.

    Arm title
    		 PPMS Cohort: Ocrelizumab + LP
    Arm description
    		 For the PPMS cohort, ocrelizumab will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks during the treatment period and then as a single 600-mg dose every 24 weeks starting week 72 during the Long-Term Extension period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    RO4964913
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Ocrelizumab will be administered as IV infusion.

    Investigational medicinal product name
    Methyloprednisolone
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants will receive 100 mg of IV methylprenisolone (or an equivalent) prior to ocrelizumab infusion.

    Investigational medicinal product name
    Antihistamine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Participants will receive an antihistamine, such as diphenhydramine, prior to ocrelizumab infusion.

    Number of subjects in period 1
    		RMS Cohort Arm 1: Ocrelizumab + LP RMS Cohort Arm 2: Ocrelizumab + LP RMS Cohort Arm 3: Ocrelizumab + LP RMS Cohort Arm 4: Ocrelizumab + LP PPMS Cohort: Ocrelizumab + LP
    Started
    23
    31
    28
    18
    31
    Completed
    0
    0
    0
    0
    1
    Not completed
    23
    31
    28
    18
    30
         Adverse event, serious fatal
    -
    -
    -
    -
    1
         Consent withdrawn by subject
    2
    8
    7
    1
    4
         Physician decision
    2
    2
    -
    -
    1
         Adverse event, non-fatal
    1
    2
    2
    -
    -
         Study Terminated By Sponsor
    -
    -
    -
    1
    -
         Not specified
    3
    4
    1
    -
    -
         Continued Onto Commercially Available Ocrelizumab
    12
    12
    14
    14
    21
         Non-Compliance With Study Drug
    1
    3
    1
    -
    1
         Pregnancy
    -
    -
    2
    1
    -
         Lost to follow-up
    2
    -
    1
    1
    1
         Lack of efficacy
    -
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    RMS Cohort Arm 1: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 12. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 2: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 24. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 3: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 4: Ocrelizumab + LP
    Reporting group description
    		 Ocrelizumab treatment will be delayed for 12 weeks from pre-treatment baseline. Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP at Week -12 (pre-treatment baseline) and a second LP before the start of dosing (Week 1, treatment baseline). Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    PPMS Cohort: Ocrelizumab + LP
    Reporting group description
    		 For the PPMS cohort, ocrelizumab will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks during the treatment period and then as a single 600-mg dose every 24 weeks starting week 72 during the Long-Term Extension period.

    Reporting group values
    		 RMS Cohort Arm 1: Ocrelizumab + LP RMS Cohort Arm 2: Ocrelizumab + LP RMS Cohort Arm 3: Ocrelizumab + LP RMS Cohort Arm 4: Ocrelizumab + LP PPMS Cohort: Ocrelizumab + LP Total
    Number of subjects
    		 23 31 28 18 31 131
    Age Categorical
    Units: Participants
        <=18 years
    		 0 0 0 0 0 0
        Between 18 and 65 years
    		 23 31 28 18 31 131
        >=65 years
    		 0 0 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 36.0 ( 10.4 ) 38.7 ( 10.4 ) 34.6 ( 10.8 ) 36.4 ( 9.8 ) 44.9 ( 7.4 ) -
    Sex/Gender, Customized
    Units: Participants
        Male
    		 8 9 8 7 16 48
        Female
    		 15 22 20 11 15 83
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0
        Asian
    		 0 0 1 1 1 3
        Native Hawaiian or Other Pacific Islander
    		 0 0 0 0 0 0
        Black or African American
    		 2 3 1 3 0 9
        White
    		 21 28 25 13 29 116
        More than one race
    		 0 0 0 1 0 1
        Unknown or Not Reported
    		 0 0 1 0 1 2
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 1 2 1 0 2 6
        Not Hispanic or Latino
    		 22 28 27 17 28 122
        Unknown or Not Reported
    		 0 1 0 1 1 3

    End points

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    End points reporting groups
    Reporting group title
    RMS Cohort Arm 1: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 12. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 2: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 24. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 3: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 4: Ocrelizumab + LP
    Reporting group description
    		 Ocrelizumab treatment will be delayed for 12 weeks from pre-treatment baseline. Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP at Week -12 (pre-treatment baseline) and a second LP before the start of dosing (Week 1, treatment baseline). Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    PPMS Cohort: Ocrelizumab + LP
    Reporting group description
    		 For the PPMS cohort, ocrelizumab will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks during the treatment period and then as a single 600-mg dose every 24 weeks starting week 72 during the Long-Term Extension period.

    Primary: Change in Levels of NfL (neurofilament light) in CSF from Treatment Baseline to Post-Treatment with Ocrelizumab

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    End point title
    		 Change in Levels of NfL (neurofilament light) in CSF from Treatment Baseline to Post-Treatment with Ocrelizumab [1]
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
    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: No analysis provided
    End point values
    		 RMS Cohort Arm 1: Ocrelizumab + LP RMS Cohort Arm 2: Ocrelizumab + LP RMS Cohort Arm 3: Ocrelizumab + LP RMS Cohort Arm 4: Ocrelizumab + LP PPMS Cohort: Ocrelizumab + LP
    Number of subjects analysed
    21
    25
    22
    16
    28
    Units: pg/mL
    arithmetic mean (standard deviation)
        Primary Analysis
    -1232.97 ( 2060.37 )
    -1169.13 ( 1739.49 )
    -1008.13 ( 1132.68 )
    -931.83 ( 2816.27 )
    261.85 ( 1175.72 )
        LTE phase Week 144
    -2331.89 ( 3334.80 )
    -644.50 ( 1371.39 )
    -1287.58 ( 1822.72 )
    -2544.33 ( 3807.94 )
    -925.32 ( 2507.97 )
        LTE phase Week 240
    -2499.98 ( 3606.71 )
    -791.51 ( 1150.89 )
    -1060.33 ( 1678.95 )
    -5488.70 ( 4350.46 )
    -1221.33 ( 2738.19 )
    No statistical analyses for this end point

    Primary: Change in Number of CD19+ B cells in CSF from Treatment Baseline to Post-Treatment with Ocrelizumab

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    End point title
    		 Change in Number of CD19+ B cells in CSF from Treatment Baseline to Post-Treatment with Ocrelizumab [2]
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
    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: No analysis provided
    End point values
    		 RMS Cohort Arm 1: Ocrelizumab + LP RMS Cohort Arm 2: Ocrelizumab + LP RMS Cohort Arm 3: Ocrelizumab + LP RMS Cohort Arm 4: Ocrelizumab + LP PPMS Cohort: Ocrelizumab + LP
    Number of subjects analysed
    21
    25
    22
    16
    28
    Units: cells/μL
    arithmetic mean (standard deviation)
        Primary Analysis
    -0.22 ( 0.26 )
    -0.15 ( 0.36 )
    -0.13 ( 0.32 )
    -0.18 ( 0.37 )
    -0.09 ( 0.11 )
        LTE phase Week 144
    -0.11 ( 0.08 )
    -0.14 ( 0.20 )
    -0.06 ( 0.23 )
    0.15 ( 0.10 )
    -0.01 ( 0.09 )
        LTE phase Week 240
    -0.08 ( 0.09 )
    -0.20 ( 0.26 )
    -0.02 ( 0.01 )
    -0.04 ( 0.05 )
    0.01 ( 0.03 )
    No statistical analyses for this end point

    Primary: Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab

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    End point title
    		 Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab [3]
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline to post-treatment (Week 12, 24, 52 according to randomization and Weeks 144 and 240)
    Notes
    [3] - 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: No analysis provided
    End point values
    		 RMS Cohort Arm 1: Ocrelizumab + LP RMS Cohort Arm 2: Ocrelizumab + LP RMS Cohort Arm 3: Ocrelizumab + LP RMS Cohort Arm 4: Ocrelizumab + LP PPMS Cohort: Ocrelizumab + LP
    Number of subjects analysed
    21
    25
    22
    16
    28
    Units: cells/μL
    arithmetic mean (standard deviation)
        Primary Analysis
    -6.61 ( 10.48 )
    -1.92 ( 3.15 )
    -1.46 ( 2.67 )
    -1.98 ( 5.10 )
    -3.25 ( 4.32 )
        LTE phase Week 144
    -3.45 ( 2.33 )
    1.78 ( 9.76 )
    -0.83 ( 4.64 )
    2.25 ( 0.17 )
    -3.62 ( 5.56 )
        LTE phase Week 240
    -3.00 ( 3.16 )
    -3.47 ( 2.31 )
    -1.41 ( 1.30 )
    -1.67 ( 2.42 )
    -1.37 ( 0.54 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline up to 5 years
    Adverse event reporting additional description
    Safety population is defined as all enrolled patients who received at least one infusion of ocrelizumab, even if the infusion was incomplete.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    RMS Cohort Arm 1: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 12. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 2: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 24. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    PPMS Cohort: Ocrelizumab + LP
    Reporting group description
    		 For the PPMS cohort, ocrelizumab will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks during the treatment period and then as a single 600-mg dose every 24 weeks starting week 72 during the Long-Term Extension period.

    Reporting group title
    RMS Cohort Arm 4: Ocrelizumab + LP
    Reporting group description
    		 Ocrelizumab treatment will be delayed for 12 weeks from pre-treatment baseline. Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP at Week -12 (pre-treatment baseline) and a second LP before the start of dosing (Week 1, treatment baseline). Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Reporting group title
    RMS Cohort Arm 3: Ocrelizumab + LP
    Reporting group description
    		 Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.

    Serious adverse events
    		 RMS Cohort Arm 1: Ocrelizumab + LP RMS Cohort Arm 2: Ocrelizumab + LP PPMS Cohort: Ocrelizumab + LP RMS Cohort Arm 4: Ocrelizumab + LP RMS Cohort Arm 3: Ocrelizumab + LP
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 23 (21.74%)
    5 / 31 (16.13%)
    9 / 31 (29.03%)
    5 / 18 (27.78%)
    1 / 28 (3.57%)
         number of deaths (all causes)
    1
    0
    1
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Eye injury
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Seizure
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myelitis transverse
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple sclerosis relapse
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Crohn's disease
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Umbilical hernia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Assisted suicide
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Bipolar disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mania
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Completed suicide
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seronegative arthritis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 RMS Cohort Arm 1: Ocrelizumab + LP RMS Cohort Arm 2: Ocrelizumab + LP PPMS Cohort: Ocrelizumab + LP RMS Cohort Arm 4: Ocrelizumab + LP RMS Cohort Arm 3: Ocrelizumab + LP
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    23 / 23 (100.00%)
    28 / 31 (90.32%)
    31 / 31 (100.00%)
    17 / 18 (94.44%)
    27 / 28 (96.43%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vascular disorders
    Vasculitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Peripheral coldness
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    1
    3
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    6
    1
    4
    Gait disturbance
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Fatigue
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 31 (6.45%)
    5 / 31 (16.13%)
    4 / 18 (22.22%)
    3 / 28 (10.71%)
         occurrences all number
    1
    2
    10
    8
    3
    Facial pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    0
    0
    2
    Chest discomfort
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    Pain
         subjects affected / exposed
    2 / 23 (8.70%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    2
    1
    1
    1
    0
    Puncture site pain
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    Peripheral swelling
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    0
    4
    0
    0
    Pyrexia
         subjects affected / exposed
    1 / 23 (4.35%)
    3 / 31 (9.68%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    4
    4
    1
    1
    Vessel puncture site pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Immune system disorders
    Seasonal allergy
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    1
    1
    1
    1
    Reproductive system and breast disorders
    Breast cyst
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    Cough
         subjects affected / exposed
    2 / 23 (8.70%)
    1 / 31 (3.23%)
    8 / 31 (25.81%)
    2 / 18 (11.11%)
    3 / 28 (10.71%)
         occurrences all number
    2
    1
    8
    2
    3
    Hiccups
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nasal congestion
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    1
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    2 / 28 (7.14%)
         occurrences all number
    2
    0
    1
    2
    2
    Psychiatric disorders
    Sleep disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Anxiety
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    2
    1
    1
    Attention deficit hyperactivity disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Depressed mood
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Depression
         subjects affected / exposed
    2 / 23 (8.70%)
    2 / 31 (6.45%)
    5 / 31 (16.13%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    2
    5
    0
    1
    Insomnia
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    3 / 28 (10.71%)
         occurrences all number
    0
    1
    2
    1
    3
    Panic attack
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Restlessness
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Somnambulism
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Investigations
    Blood iron decreased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Body temperature increased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Influenza A virus test positive
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Occult blood
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Weight increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    0
    1
    2
    0
    1
    Blood uric acid increased
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Chillblains
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Contusion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    3 / 18 (16.67%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    3
    3
    0
    Fall
         subjects affected / exposed
    2 / 23 (8.70%)
    2 / 31 (6.45%)
    5 / 31 (16.13%)
    2 / 18 (11.11%)
    4 / 28 (14.29%)
         occurrences all number
    2
    2
    9
    2
    5
    Infusion related reaction
         subjects affected / exposed
    15 / 23 (65.22%)
    9 / 31 (29.03%)
    12 / 31 (38.71%)
    11 / 18 (61.11%)
    16 / 28 (57.14%)
         occurrences all number
    36
    13
    38
    16
    32
    Joint dislocation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Ligament sprain
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    2
    1
    1
    Limb injury
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    2
    2
    0
    Post lumbar puncture syndrome
         subjects affected / exposed
    2 / 23 (8.70%)
    4 / 31 (12.90%)
    6 / 31 (19.35%)
    4 / 18 (22.22%)
    4 / 28 (14.29%)
         occurrences all number
    3
    5
    8
    4
    7
    Post procedural contusion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Procedural dizziness
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 31 (6.45%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    2
    2
    3
    0
    2
    Road traffic accident
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    4
    0
    1
    2
    0
    Skin abrasion
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    2
    1
    0
    Thermal burn
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    4 / 31 (12.90%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    4
    0
    1
    Palpitations
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Nervous system disorders
    Multiple sclerosis pseudo relapse
         subjects affected / exposed
    3 / 23 (13.04%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    5
    0
    0
    2
    0
    Balance disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    4 / 31 (12.90%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Burning sensation
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    1
    1
    3
    Cognitive disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Coordination abnormal
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dizziness
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    1
    3
    0
    2
    Dysarthria
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    0
    0
    0
    1
    1
    Headache
         subjects affected / exposed
    2 / 23 (8.70%)
    6 / 31 (19.35%)
    5 / 31 (16.13%)
    4 / 18 (22.22%)
    4 / 28 (14.29%)
         occurrences all number
    4
    10
    5
    5
    4
    Hypoaesthesia
         subjects affected / exposed
    2 / 23 (8.70%)
    1 / 31 (3.23%)
    4 / 31 (12.90%)
    2 / 18 (11.11%)
    4 / 28 (14.29%)
         occurrences all number
    2
    1
    6
    5
    4
    Lhermitte's sign
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    0
    0
    3
    Migraine
         subjects affected / exposed
    2 / 23 (8.70%)
    4 / 31 (12.90%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    2
    4
    0
    1
    0
    Multiple sclerosis
         subjects affected / exposed
    3 / 23 (13.04%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Muscle spasticity
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Restless arm syndrome
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Restless legs syndrome
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Sensory disturbance
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Sinus headache
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 31 (6.45%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Somnolence
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Tremor
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    1
    2
    0
    0
    Paraesthesia
         subjects affected / exposed
    3 / 23 (13.04%)
    2 / 31 (6.45%)
    4 / 31 (12.90%)
    2 / 18 (11.11%)
    4 / 28 (14.29%)
         occurrences all number
    4
    3
    7
    3
    5
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    0
    0
    0
    1
    1
    Lymphadenopathy
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    1
    0
    0
    0
    2
    Lymphopenia
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0
    Ear and labyrinth disorders
    Ear discomfort
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Inner ear inflammation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tinnitus
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    2
    0
    1
    1
    1
    Vertigo
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    2
    0
    0
    2
    Eye disorders
    Vision blurred
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    2 / 18 (11.11%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    2
    2
    1
    Ocular hyperaemia
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Eye pain
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    2 / 18 (11.11%)
    1 / 28 (3.57%)
         occurrences all number
    0
    0
    0
    2
    1
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Abdominal distension
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    Abdominal pain
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 31 (6.45%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    1
    2
    0
    1
    0
    Anal incontinence
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    2
    0
    0
    0
    0
    Constipation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Diarrhoea
         subjects affected / exposed
    3 / 23 (13.04%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    2 / 18 (11.11%)
    2 / 28 (7.14%)
         occurrences all number
    3
    1
    2
    2
    2
    Diverticulum
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    3
    0
    Vomiting
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    1
    0
    2
    1
    0
    Nausea
         subjects affected / exposed
    1 / 23 (4.35%)
    3 / 31 (9.68%)
    2 / 31 (6.45%)
    3 / 18 (16.67%)
    4 / 28 (14.29%)
         occurrences all number
    1
    3
    3
    3
    5
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    3 / 18 (16.67%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Food poisoning
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    2
    0
    Dysphagia
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Eczema
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    0
    1
    2
    Acne
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Alopecia
         subjects affected / exposed
    0 / 23 (0.00%)
    3 / 31 (9.68%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    0
    3
    2
    1
    1
    Dermatitis allergic
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Dry skin
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Erythema
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Hand dermatitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    1
    1
    1
    Psoriasis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Rash
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 31 (6.45%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    3 / 28 (10.71%)
         occurrences all number
    0
    2
    2
    1
    5
    Rosacea
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Skin fissures
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    2
    0
    1
    Rash erythematous
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Renal and urinary disorders
    Micturition urgency
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    0
    0
    2
    1
    1
    Urinary hesitation
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Urinary retention
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Dysuria
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Neck pain
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    1
    0
    3
    0
    4
    Arthralgia
         subjects affected / exposed
    2 / 23 (8.70%)
    3 / 31 (9.68%)
    11 / 31 (35.48%)
    2 / 18 (11.11%)
    4 / 28 (14.29%)
         occurrences all number
    2
    3
    14
    3
    5
    Back pain
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    9 / 31 (29.03%)
    4 / 18 (22.22%)
    2 / 28 (7.14%)
         occurrences all number
    1
    0
    10
    4
    2
    Flank pain
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Limb discomfort
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    1
    3
    0
    0
    Muscle spasms
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    3 / 31 (9.68%)
    1 / 18 (5.56%)
    3 / 28 (10.71%)
         occurrences all number
    0
    1
    4
    1
    5
    Muscle tightness
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Muscular weakness
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    4 / 31 (12.90%)
    2 / 18 (11.11%)
    2 / 28 (7.14%)
         occurrences all number
    1
    1
    5
    2
    3
    Musculoskeletal stiffness
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    3 / 31 (9.68%)
    0 / 18 (0.00%)
    1 / 28 (3.57%)
         occurrences all number
    0
    0
    3
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    3 / 31 (9.68%)
    2 / 18 (11.11%)
    0 / 28 (0.00%)
         occurrences all number
    1
    1
    4
    3
    0
    Pain in extremity
         subjects affected / exposed
    3 / 23 (13.04%)
    4 / 31 (12.90%)
    3 / 31 (9.68%)
    3 / 18 (16.67%)
    5 / 28 (17.86%)
         occurrences all number
    3
    5
    7
    6
    6
    Tendonitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Tendon disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Infections and infestations
    Influenza
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 31 (6.45%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    1
    2
    2
    0
    2
    Infected cyst
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Impetigo
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 31 (6.45%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    2
    3
    1
    1
    Gastrointestinal infection
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    3
    0
    0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Ear infection
         subjects affected / exposed
    2 / 23 (8.70%)
    3 / 31 (9.68%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    2 / 28 (7.14%)
         occurrences all number
    2
    3
    0
    1
    2
    Conjunctivitis
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    2
    2
    0
    0
    COVID-19
         subjects affected / exposed
    4 / 23 (17.39%)
    2 / 31 (6.45%)
    5 / 31 (16.13%)
    4 / 18 (22.22%)
    1 / 28 (3.57%)
         occurrences all number
    4
    2
    5
    4
    1
    Bronchitis
         subjects affected / exposed
    1 / 23 (4.35%)
    5 / 31 (16.13%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    2 / 28 (7.14%)
         occurrences all number
    1
    5
    1
    1
    3
    Gastroenteritis
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    1
    1
    2
    1
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 23 (30.43%)
    6 / 31 (19.35%)
    13 / 31 (41.94%)
    12 / 18 (66.67%)
    10 / 28 (35.71%)
         occurrences all number
    10
    12
    22
    28
    19
    Urinary tract infection
         subjects affected / exposed
    4 / 23 (17.39%)
    5 / 31 (16.13%)
    11 / 31 (35.48%)
    7 / 18 (38.89%)
    5 / 28 (17.86%)
         occurrences all number
    5
    6
    41
    14
    9
    Tooth infection
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    1 / 28 (3.57%)
         occurrences all number
    1
    0
    0
    1
    1
    Sinusitis
         subjects affected / exposed
    4 / 23 (17.39%)
    10 / 31 (32.26%)
    2 / 31 (6.45%)
    1 / 18 (5.56%)
    4 / 28 (14.29%)
         occurrences all number
    5
    13
    2
    1
    5
    Rhinitis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    2
    0
    0
    Pyelonephritis
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Pneumonia
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 31 (6.45%)
    4 / 31 (12.90%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    2
    4
    0
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    2 / 28 (7.14%)
         occurrences all number
    0
    0
    0
    0
    2
    Pharyngitis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 31 (3.23%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    1
    1
    1
    0
    Oral herpes
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    2 / 31 (6.45%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    1
    2
    0
    0
    Oral candidiasis
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 31 (6.45%)
    1 / 31 (3.23%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    0
    3
    1
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 31 (3.23%)
    5 / 31 (16.13%)
    2 / 18 (11.11%)
    3 / 28 (10.71%)
         occurrences all number
    1
    1
    6
    2
    4
    Vaginal infection
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Nail bed infection
         subjects affected / exposed
    0 / 23 (0.00%)
    0 / 31 (0.00%)
    0 / 31 (0.00%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Viral infection
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 31 (6.45%)
    0 / 31 (0.00%)
    0 / 18 (0.00%)
    0 / 28 (0.00%)
         occurrences all number
    1
    2
    0
    0
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 31 (6.45%)
    1 / 31 (3.23%)
    1 / 18 (5.56%)
    0 / 28 (0.00%)
         occurrences all number
    0
    2
    1
    1
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Nov 2016
    The protocol was expanded to include a control arm (Arm 4) to the RMS cohort that would allow for an estimate of the natural variability of the disease when analyzing other cohort arms
    29 Sep 2017
    A long-term extension (LTE) phase, beginning at Week 72 and continuing for up to 4 years, was added to collect additional safety and efficacy information
    18 Dec 2020
    The protocol was amended to incorporate an optional shorter study drug infusion regimen for patients enrolled in the LTE phase

    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
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    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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