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    Clinical Trial Results:
    A Randomised, Double-Blind, Placebo Controlled, Parallel-Group, Multicenter Study To Evaluate The Efficacy and Safety of Two Doses of Ocrelizumab in Patients With WHO or ISN Class III or IV Nephritis Due To Systemic Lupus Erythematosus

    Summary
    EudraCT number
    		 2006-005357-29
    Trial protocol
    		 GB   FR   DE   HU   ES   NL   PT   SE   PL   BG  
    Global end of trial date
    28 Oct 2013

    Results information
    Results version number
    		 v2(current)
    This version publication date
    19 May 2016
    First version publication date
    07 Aug 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    2 data eras identified as part of QC that require correction

    Trial information

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    Trial identification
    Sponsor protocol code
    WA20500
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00626197
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline , F. Hoffmann-La Roche AG , 41 61 6878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline , F. Hoffmann-La Roche AG , 41 61 6878333, global.trial_information@roche.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
    19 Nov 2013
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Oct 2013
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To investigate the ability of the ocrelizumab regimen in combination with Standard Of Care (SOC) treatment to induce a complete or partial renal response, as assessed by renal function, urinary sediment and proteinuria in participants with International Society of Nephrology/Renal Pathology Society (ISN/RPS) or World Health Organization (WHO) class III or IV lupus nephritis.
    Protection of trial subjects
    The investigator ensured that this study was conducted in full conformance with the principles of the “Declaration of Helsinki” or with the laws and regulations of the country in which the research was conducted, whichever afforded the greater protection to the individual and fully adhered to the principles outlined in “Guideline for Good Clinical Practice” International Conference on Harmonisation (ICH) Tripartite Guideline [January 1997] or with local law if it affords greater protection to the participant. For studies conducted in the European Union/European Economic Area (EU/EEA) countries, the investigator ensured compliance with the EU Clinical Trial Directive [2001/20/EC]. For studies conducted in the United State of America (USA) or under US Investigational new drug (IND), the investigator additionally ensured that the basic principles of “Good Clinical Practice” as outlined in the current version of 21 CFR, subchapter D, part 312, “Responsibilities of Sponsors and Investigators”, part 50, “Protection of Human Patients”, and part 56, “Institutional Review Boards”, were adhered to.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Feb 2008
    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
    Netherlands: 6
    Country: Number of subjects enrolled
    Spain: 10
    Country: Number of subjects enrolled
    Sweden: 1
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    Bulgaria: 10
    Country: Number of subjects enrolled
    France: 18
    Country: Number of subjects enrolled
    Germany: 10
    Country: Number of subjects enrolled
    Hungary: 11
    Country: Number of subjects enrolled
    Argentina: 56
    Country: Number of subjects enrolled
    Brazil: 18
    Country: Number of subjects enrolled
    Canada: 3
    Country: Number of subjects enrolled
    Chile: 2
    Country: Number of subjects enrolled
    Colombia: 43
    Country: Number of subjects enrolled
    Costa Rica: 4
    Country: Number of subjects enrolled
    Hong Kong: 5
    Country: Number of subjects enrolled
    Indonesia: 3
    Country: Number of subjects enrolled
    Malaysia: 18
    Country: Number of subjects enrolled
    Mexico: 21
    Country: Number of subjects enrolled
    Peru: 16
    Country: Number of subjects enrolled
    Philippines: 15
    Country: Number of subjects enrolled
    Russian Federation: 10
    Country: Number of subjects enrolled
    Serbia: 5
    Country: Number of subjects enrolled
    South Africa: 5
    Country: Number of subjects enrolled
    Korea, Republic of: 17
    Country: Number of subjects enrolled
    Taiwan: 8
    Country: Number of subjects enrolled
    Thailand: 22
    Country: Number of subjects enrolled
    Turkey: 4
    Country: Number of subjects enrolled
    United States: 36
    Worldwide total number of subjects
    381
    EEA total number of subjects
    70
    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)
    7
    Adults (18-64 years)
    372
    From 65 to 84 years
    2
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Screening was done from Day -14 to Day -1.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received placebo IV on days 1 and 15, followed by placebo IV at Week 16 and then every 16 weeks up to 48 weeks.

    Arm title
    		 Ocrelizumab 400 mg
    Arm description
    		 Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    RO4964913
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received ocrelizumab on Days 1 and 15, followed by 400 mg IV at Week 16 and then every 16 weeks up to 48 weeks.

    Arm title
    		 Ocrelizumab 1000 mg
    Arm description
    		 Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ocrelizumab
    Investigational medicinal product code
    Other name
    RO4964913
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received ocrelizumab on Days 1 and 15, followed by 1000 mg IV at Week 16 and then every 16 weeks up to 48 weeks.

    Number of subjects in period 1
    		Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg
    Started
    126
    127
    128
    Completed
    49
    83
    74
    Not completed
    77
    44
    54
         Adverse event, serious fatal
    6
    3
    6
         Consent withdrawn by subject
    7
    17
    17
         Failure to return
    6
    6
    5
         Adverse event, non-fatal
    2
    1
    1
         Administrative reasons
    55
    15
    19
         Did not cooperate
    1
    2
    6

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Reporting group title
    Ocrelizumab 400 mg
    Reporting group description
    		 Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Reporting group title
    Ocrelizumab 1000 mg
    Reporting group description
    		 Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Reporting group values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg Total
    Number of subjects
    		 126 127 128 381
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 31.3 ( 9.9 ) 31.9 ( 10.2 ) 30.6 ( 8.9 ) -
    Gender categorical
    Units: Subjects
        Female
    		 107 115 110 332
        Male
    		 19 12 18 49

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Reporting group title
    Ocrelizumab 400 mg
    Reporting group description
    		 Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Reporting group title
    Ocrelizumab 1000 mg
    Reporting group description
    		 Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Subject analysis set title
    OCR + SOC
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    This analysis set included all participants who were treated with ocrelizumab (OCR).

    Subject analysis set title
    Placebo-Mycophenolate Mofetil (MMF)
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Placebo - MMF group included participants whose SOC treatment included MMF as an immunosuppressant treatment.

    Subject analysis set title
    Placebo-Euro Lupus (EL)
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Placebo-EL group included participants whose SOC treatment included Cyclophosphamide (Euro-lupus) as part of the immunosuppressant treatment.

    Primary: Percentage of Participants who Achieved a Complete Renal Response (CRR) or a Partial Renal Response (PRR) at Week 48

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    End point title
    		 Percentage of Participants who Achieved a Complete Renal Response (CRR) or a Partial Renal Response (PRR) at Week 48 [1]
    End point description
    CRR was defined as: 1. Normal serum creatinine (and with no more than a 25 percent [%] increase from Baseline); 2. Improvement in urinary protein:urinary creatinine ratio to less than or equal to (≤) 0.5. PRR was defined as at least 50 percent (%) reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was greater than (>) 3, a urine protein:urine creatinine ratio of less than (<) 3 needed to be achieved.
    End point type
    Primary
    End point timeframe
    Week 48
    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: The primary endpoint was analyzed via an overall response (CRR+PRR) analysis and the separate complete and partial response rates were only summarized descriptively.
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    75
    75
    73
    148
    Units: Percentage of participants
    number (not applicable)
        CRR
    34.7
    42.7
    31.5
    37.2
        PRR
    20
    24
    35.6
    29.7
    No statistical analyses for this end point

    Primary: Percentage of Participants Who Achieved Overall Response

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    End point title
    		 Percentage of Participants Who Achieved Overall Response
    End point description
    Overall response rate (ORR) equals (=) CRR + PRR. CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from baseline) 2. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio is >3, a urine protein:urine creatinine ratio of <3 needs to be achieved.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    75
    75
    73
    148
    Units: Percentage of Participants
        number (confidence interval 95%)
    54.7 (43.4 to 65.9)
    66.7 (56 to 77.3)
    67.1 (56.3 to 77.9)
    66.9 (59.3 to 74.5)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Placebo v Ocrelizumab 400 mg
    Number of subjects included in analysis
    150
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    12.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.3
         upper limit
    		 27.5
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    Placebo v Ocrelizumab 1000 mg
    Number of subjects included in analysis
    148
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 Mean difference (final values)
    Point estimate
    13.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.4
         upper limit
    		 29.2
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    Placebo v OCR + SOC
    Number of subjects included in analysis
    223
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.065
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Mean difference (final values)
    Point estimate
    12.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.8
         upper limit
    		 26.1

    Secondary: Percentage of Participants who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48

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    End point title
    		 Percentage of Participants who Achieved a Renal Response (Partial or Complete) by Week 36, and Sustain or Improve This Response Until Week 48
    End point description
    CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50 % reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein:urine creatinine ratio of <3 needed to be achieved.
    End point type
    Secondary
    End point timeframe
    Weeks 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    0 [5]
    Units: Percentage of Participants
        number (not applicable)
    Notes
    [2] - Due to early termination of the study, no secondary outcome analyses were performed.
    [3] - Due to early termination of the study, no secondary outcome analyses were performed.
    [4] - Due to early termination of the study, no secondary outcome analyses were performed.
    [5] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Time to Complete Renal Response

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    End point title
    		 Time to Complete Renal Response
    End point description
    Time to complete renal response was proposed to be analyzed using a stratified log rank test with race and SOC as stratification factors. Comparisons of ocrelizumab versus placebo were to be expressed as p-values, estimated hazard ratios, adjusted proportions of participants who achieved a complete renal response and their 95% confidence intervals. Kaplan-Meier curves were to be produced. Due to early termination of the study the analyses were not performed.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [6]
    0 [7]
    0 [8]
    0 [9]
    Units: Weeks
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [6] - Due to early termination of the study, no secondary outcome analyses were performed.
    [7] - Due to early termination of the study, no secondary outcome analyses were performed.
    [8] - Due to early termination of the study, no secondary outcome analyses were performed.
    [9] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48

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    End point title
    		 Area Under the Curve (AUC) of Calculated Glomerular Filtration Rate (cGFR) Between Baseline and Week 48
    End point description
    The improvement of AUC of cGFR was to be measured between Baseline and Week 48. This was to be analyzed with Analysis of Covariance (ANCOVA) with race and SOC as covariates.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and Week 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [10]
    0 [11]
    0 [12]
    0 [13]
    Units: mL/min)*weeks
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [10] - Due to early termination of the study, no secondary outcome analyses were performed.
    [11] - Due to early termination of the study, no secondary outcome analyses were performed.
    [12] - Due to early termination of the study, no secondary outcome analyses were performed.
    [13] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score

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    End point title
    		 Percentage of Participants Who Achieved A Reduction In Systemic Lupus Erythematosis Disease Activity Index (SLEDAI) -2K Score
    End point description
    SLEDAI-2K measures disease activity at the visit or within the preceding 10 days. It comprised of 24 descriptors, covering 9 organ systems, and reflects disease activity over the previous 10 days.The total SLEDAI-2K score falls between 0 and 105, with higher scores representing higher disease activity
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [14]
    0 [15]
    0 [16]
    0 [17]
    Units: percentage of participants
        number (not applicable)
    Notes
    [14] - Due to early termination of the study, no secondary outcome analyses were performed.
    [15] - Due to early termination of the study, no secondary outcome analyses were performed.
    [16] - Due to early termination of the study, no secondary outcome analyses were performed.
    [17] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Time to First Renal Flare In Those Participants who Demonstrated at least a Partial Renal Response

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    End point title
    		 Time to First Renal Flare In Those Participants who Demonstrated at least a Partial Renal Response
    End point description
    Renal flares may be either proteinuric or nephritic as defined below: Proteinuric Flares are defined as follows:In participants who achieve a urine protein:urine creatinine (Upr:Ucr) ≤ 0.5, an increase to Upr:Ucr >1; In participants with an Upr:Ucr >0.5, a doubling of Upr:Ucr (with a minimum increase to Upr:Ucr >2). Nephritic Flare defined as: Increase in serum creatinine of ≥30% from the lowest value achieved in the study accompanied by Increase Upr:Ucr >1 Or New/worsening active urine sediment on two consecutive occasions, in the absence of urinary tract infection or other causes of hematuria.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [18]
    0 [19]
    0 [20]
    0 [21]
    Units: Weeks
        median (full range (min-max))
    ( to )
    ( to )
    ( to )
    ( to )
    Notes
    [18] - Due to early termination of the study, no secondary outcome analyses were performed.
    [19] - Due to early termination of the study, no secondary outcome analyses were performed.
    [20] - Due to early termination of the study, no secondary outcome analyses were performed.
    [21] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) from Baseline to Week 48

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    End point title
    		 Percentage of Participants Who Achieved Clinically Meaningful Improvement in the Physical and Mental Component Scores of the Short Form 36 (SF36) from Baseline to Week 48
    End point description
    The SF36 Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale. A score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions physical role functioning, emotional role functioning, social role functioning, and mental health.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 12, 24, 36, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [22]
    0 [23]
    0 [24]
    0 [25]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [22] - Due to early termination of the study, no secondary outcome analyses were performed.
    [23] - Due to early termination of the study, no secondary outcome analyses were performed.
    [24] - Due to early termination of the study, no secondary outcome analyses were performed.
    [25] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire from Baseline to Week 48

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    End point title
    		 Percentage of Participants Who Achieved Clinically Meaningful Improvement in Fatigue Using the Functional Assessment of Chronic Illness Therapy (Facit) Fatigue Questionnaire from Baseline to Week 48
    End point description
    The FACIT Fatigue Scale is a short, 13-item, easy-to-administer tool that measures an individual’s level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four point Likert scale (4 = not at all fatigued to 0 = very much fatigued).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [26]
    0 [27]
    0 [28]
    0 [29]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [26] - Due to early termination of the study, no secondary outcome analyses were performed.
    [27] - Due to early termination of the study, no secondary outcome analyses were performed.
    [28] - Due to early termination of the study, no secondary outcome analyses were performed.
    [29] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) from Baseline to Week 48

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    End point title
    		 Percentage of Participants Who Achieved Clinically Meaningful Improvement in Pain Using the Modified Brief Pain Inventory Short Form (mBPI-SF) from Baseline to Week 48
    End point description
    m-BPI-sf is a self-administered 11-point Likert rating scale to rate pain in the past 24 hours. A single item pertains to worst pain in the past 24 hours with a range of 0 (no pain) to 10 (worst imaginable pain).
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 12, 24, 36, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [30]
    0 [31]
    0 [32]
    0 [33]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [30] - Due to early termination of the study, no secondary outcome analyses were performed.
    [31] - Due to early termination of the study, no secondary outcome analyses were performed.
    [32] - Due to early termination of the study, no secondary outcome analyses were performed.
    [33] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Health Care Visits Over the 48-Week Treatment Period

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    End point title
    		 Health Care Visits Over the 48-Week Treatment Period
    End point description
    The number of health care visits (including doctor’s office visits, Emergency room/ Accident and Emergency [ER/A&E] visits and hospitalizations) over the 48-week treatment period were recorded.
    End point type
    Secondary
    End point timeframe
    Weeks 1, 24, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [34]
    0 [35]
    0 [36]
    0 [37]
    Units: visits
        number (not applicable)
    Notes
    [34] - Due to early termination of the study, no secondary outcome analyses were performed.
    [35] - Due to early termination of the study, no secondary outcome analyses were performed.
    [36] - Due to early termination of the study, no secondary outcome analyses were performed.
    [37] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved a CRR or PRR And who Received A Corticosteroid dose of <10 Milligrams per Day (mg/day) from Week 24 to Week 48

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    End point title
    		 Percentage of Participants who Achieved a CRR or PRR And who Received A Corticosteroid dose of <10 Milligrams per Day (mg/day) from Week 24 to Week 48
    End point description
    CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein:urine creatinine ratio of <3 needed to be achieved.
    End point type
    Secondary
    End point timeframe
    Weeks 24, 28, 32, 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [38]
    0 [39]
    0 [40]
    0 [41]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [38] - Due to early termination of the study, no secondary outcome analyses were performed.
    [39] - Due to early termination of the study, no secondary outcome analyses were performed.
    [40] - Due to early termination of the study, no secondary outcome analyses were performed.
    [41] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Achieved a CRR or PRR And who Received a Corticosteroid Dose of <5 mg/day by Week 48

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    End point title
    		 Percentage of Participants who Achieved a CRR or PRR And who Received a Corticosteroid Dose of <5 mg/day by Week 48
    End point description
    CRR was defined as: 1. Normal serum creatinine (and with no more than a 25% increase from Baseline) 2. Inactive urinary sediment 3. Improvement in urinary protein:urinary creatinine ratio to ≤0.5. PRR was defined as at least 50% reduction in proteinuria from Baseline, without more than 25% increase of serum creatinine at Week 48, compared with Baseline. If Baseline urine protein:urine creatinine ratio was >3, a urine protein: urine creatinine ratio of <3 needed to be achieved.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [42]
    0 [43]
    0 [44]
    0 [45]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [42] - Due to early termination of the study, no secondary outcome analyses were performed.
    [43] - Due to early termination of the study, no secondary outcome analyses were performed.
    [44] - Due to early termination of the study, no secondary outcome analyses were performed.
    [45] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks

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    End point title
    		 Average Corticosteroid Burden Measured by AUC of the Cumulative Corticosteroid Dose Between 16 and 48 Weeks
    End point description
    AUC is the area under the curve (mathematically known as definite integral) in a plot of concentration of drug in blood plasma against time. AUC was to be used to determine the average corticosteroid burden.
    End point type
    Secondary
    End point timeframe
    Weeks 16, 20, 24, 28, 32, 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [46]
    0 [47]
    0 [48]
    0 [49]
    Units: (mg/mL)*weeks
        arithmetic mean (standard deviation)
    ( )
    ( )
    ( )
    ( )
    Notes
    [46] - Due to early termination of the study, no secondary outcome analyses were performed.
    [47] - Due to early termination of the study, no secondary outcome analyses were performed.
    [48] - Due to early termination of the study, no secondary outcome analyses were performed.
    [49] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Stopped Immunosuppressants After Week 48

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    End point title
    		 Percentage of Participants who Stopped Immunosuppressants After Week 48
    End point description
    The number of participants who stopped immunosuppressants were to be determined by survey.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [50]
    0 [51]
    0 [52]
    0 [53]
    Units: Percentage of participants
        number (not applicable)
    Notes
    [50] - Due to early termination of the study, no secondary outcome analyses were performed.
    [51] - Due to early termination of the study, no secondary outcome analyses were performed.
    [52] - Due to early termination of the study, no secondary outcome analyses were performed.
    [53] - Due to early termination of the study, no secondary outcome analyses were performed.
    No statistical analyses for this end point

    Secondary: Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells per Visit

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    End point title
    		 Mean Absolute Counts of Cluster of Differentiation (CD) 19 Positive (+) Cells per Visit
    End point description
    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. CD19+ cells were measured as cells per microliter (cells/uL).
    End point type
    Secondary
    End point timeframe
    Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC Placebo-Mycophenolate Mofetil (MMF) Placebo-Euro Lupus (EL)
    Number of subjects analysed
    70 [54]
    73 [55]
    70 [56]
    141 [57]
    45 [58]
    27 [59]
    Units: cells/uL
    arithmetic mean (standard deviation)
        Baseline (n=70,71,66,137,44,26)
    203.5 ( 191.4 )
    256.3 ( 300.2 )
    224.1 ( 231.7 )
    240.8 ( 268.9 )
    213.7 ( 201.7 )
    186.3 ( 175 )
        Day 15 (n=66,70,68,138,40,26)
    262.7 ( 273.9 )
    1.9 ( 1.9 )
    2.2 ( 3.4 )
    2 ( 2.7 )
    327.4 ( 324.9 )
    163.3 ( 115.8 )
        Week 4 (n=68,67,67,134,41,27)
    209.7 ( 221.4 )
    1.4 ( 2.5 )
    1.3 ( 1.6 )
    1.4 ( 2.1 )
    253.4 ( 263.9 )
    143.3 ( 107.4 )
        Week 16 (n=70,72,69,141,45,25)
    125.9 ( 186.9 )
    2.6 ( 3.6 )
    2 ( 3.8 )
    2.3 ( 3.7 )
    154.3 ( 222.2 )
    74.7 ( 75.3 )
        Week 32 (n=68,73,68,141,45,23)
    116.6 ( 154.3 )
    7.8 ( 25.8 )
    2.1 ( 2.7 )
    5.1 ( 18.8 )
    141.2 ( 172.5 )
    68.5 ( 96.8 )
        Week 48 (n=68,71,66,137,45,23)
    110 ( 114.3 )
    11.7 ( 43.6 )
    2.6 ( 8.9 )
    7.3 ( 32.2 )
    134.9 ( 123.3 )
    61.3 ( 75 )
        Day 1 Pre-infusion (n=70,71,67,138,44,26)
    203.5 ( 191.4 )
    256.3 ( 300.2 )
    222.8 ( 230.2 )
    240 ( 268 )
    213.7 ( 201.7 )
    186.3 ( 175 )
        Day 1 Post-infusion (n=70,69,68,137,43,27)
    103.1 ( 115.1 )
    11.1 ( 28.6 )
    5.7 ( 8.5 )
    8.4 ( 21.3 )
    102.4 ( 114.3 )
    104.3 ( 118.6 )
        Day 15 Pre-infusion (n=68,68,70,138,43,25)
    264.4 ( 276.6 )
    1.9 ( 1.9 )
    2.1 ( 3.3 )
    2 ( 2.7 )
    322.5 ( 323.5 )
    164.5 ( 118 )
        Day 15 Post-infusion (n=67,65,68,133,42,25)
    91.2 ( 109.2 )
    1 ( 1.3 )
    0.9 ( 1.4 )
    0.9 ( 1.3 )
    106.3 ( 130.8 )
    65.8 ( 50.4 )
        Week 16 Pre-infusion (n=67,66,66,132,43,24)
    127.8 ( 190.1 )
    2.5 ( 3.3 )
    2.1 ( 3.9 )
    2.3 ( 3.6 )
    156.5 ( 226.3 )
    76.3 ( 76.5 )
        Week 16 Post-infusion (n=61,66,66,132,40,21)
    52.7 ( 72.6 )
    1.2 ( 1.6 )
    0.8 ( 1 )
    1 ( 1.3 )
    64.2 ( 83 )
    30.9 ( 40.2 )
        Week 32 Pre-infusion (n=60,63,63,126,39,21)
    125 ( 161.1 )
    5.1 ( 16.5 )
    2 ( 2.7 )
    3.6 ( 11.8 )
    153.4 ( 180.6 )
    72.2 ( 100.4 )
        Week 32 Post-infusion (n=60,63,59,122,38,22)
    46.2 ( 54.4 )
    1 ( 1.5 )
    0.7 ( 1.4 )
    0.9 ( 1.4 )
    56.9 ( 62.5 )
    27.6 ( 29.5 )
    Notes
    [54] - number (n) = number of participants analyzed at the specified visit.
    [55] - n = number of participants analyzed at the specified visit.
    [56] - n = number of participants analyzed at the specified visit.
    [57] - n = number of participants analyzed at the specified visit.
    [58] - n = number of participants analyzed at the specified visit.
    [59] - n = number of participants analyzed at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants with CD19+ Absolute B Cell Counts <10 cells per microliter (cells/uL) by Visit

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    End point title
    		 Percentage of Participants with CD19+ Absolute B Cell Counts <10 cells per microliter (cells/uL) by Visit
    End point description
    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. n = number of participants analyzed at the specified visit. A value of of 999 denotes that no data are available for the specified data point.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC Placebo-Mycophenolate Mofetil (MMF) Placebo-Euro Lupus (EL)
    Number of subjects analysed
    70 [60]
    73 [61]
    70 [62]
    141 [63]
    45 [64]
    27 [65]
    Units: Percentage of participants
    number (not applicable)
        Baseline (n=70,71,66,137,44,26)
    4.3
    4.2
    1.5
    2.9
    6.8
    999
        Day 15 (n=66,70,68,138,40,26)
    4.5
    100
    97.1
    98.6
    7.5
    999
        Week 4 (n=68,67,67,134,41,27)
    4.4
    98.5
    100
    99.3
    7.3
    999
        Week 16 (n=70,72,69,141,45,25)
    4.3
    95.8
    97.1
    96.5
    6.7
    999
        Week 32 (n=68,73,68,141,45,23)
    7.4
    91.8
    95.6
    93.6
    8.9
    4.3
        Week 48 (n=68,71,66,137,45,23)
    5.9
    88.7
    98.5
    93.4
    4.4
    8.7
        Day 1 Pre-infusion (n=70,71,67,138,44,26)
    4.3
    4.2
    1.5
    2.9
    6.8
    999
        Day 1 Post-infusion (n=70,69,68,137,43,27)
    10
    81.2
    83.8
    82.5
    14
    3.7
        Day 15 Pre-infusion (n=68,68,70,138,43,25)
    4.4
    100
    97.1
    98.6
    7
    999
        Day 15 Post-infusion (n=67,65,68,133,42,25)
    7.5
    100
    100
    100
    11.9
    999
        Week 16 Pre-infusion (n=67,66,66,132,43,24)
    4.5
    97
    97
    97
    7
    999
        Week 16 Post-infusion (n=61,66,66,132,40,21)
    11.5
    100
    100
    100
    12.5
    9.5
        Week 32 Pre-infusion (n=60,63,63,126,39,21)
    3.3
    93.7
    95.2
    94.4
    5.1
    999
        Week 32 Post-infusion (n=60,63,59,122,38,22)
    15
    100
    100
    100
    10.5
    22.7
    Notes
    [60] - n = number of participants analyzed at the specified visit.
    [61] - n = number of participants analyzed at the specified visit.
    [62] - n = number of participants analyzed at the specified visit.
    [63] - n = number of participants analyzed at the specified visit.
    [64] - n = number of participants analyzed at the specified visit.
    [65] - n = number of participants analyzed at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants with CD19+ Absolute B Cell Counts <20 cells/uL by Visit

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    End point title
    		 Percentage of Participants with CD19+ Absolute B Cell Counts <20 cells/uL by Visit
    End point description
    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. A value of of 999 denotes that no data are available for the specified data point. n = number of participants analyzed at the specified visit.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC Placebo-Mycophenolate Mofetil (MMF) Placebo-Euro Lupus (EL)
    Number of subjects analysed
    70 [66]
    73 [67]
    70 [68]
    141 [69]
    45 [70]
    27 [71]
    Units: Percentage of participants
    number (not applicable)
        Baseline (n=70,71,66,137,44,26)
    7.1
    11.3
    3
    7.3
    11.4
    999
        Day 15 (n=66,70,68,138,40,26)
    7.6
    100
    98.5
    99.3
    10
    3.8
        Week 4 (n=68,67,67,134,41,27)
    10.3
    100
    100
    100
    12.2
    7.4
        Week 16 (n=70,72,69,141,45,25)
    11.4
    98.6
    98.6
    98.6
    13.3
    8
        Week 32 (n=68,73,68,141,45,23)
    13.2
    93.2
    100
    96.5
    15.6
    8.7
        Week 48 (n=68,71,66,137,45,23)
    17.6
    91.5
    98.5
    94.9
    13.3
    26.1
        Day 1 Pre-infusion (n=70,71,67,138,44,26)
    7.1
    11.3
    3
    7.2
    11.4
    999
        Day 1 Post-infusion (n=70,69,68,137,43,27)
    22.9
    87
    91.2
    89.1
    20.9
    25.9
        Day 15 Pre-infusion (n=68,68,70,138,43,25)
    7.4
    100
    98.6
    99.3
    9.3
    4
        Day 15 Post-infusion (n=67,65,68,133,42,25)
    17.9
    100
    100
    100
    21.4
    12
        Week 16 Pre-infusion (n=67,66,66,132,43,24)
    10.4
    98.5
    98.5
    98.5
    11.6
    8.3
        Week 16 Post-infusion (n=61,66,66,132,40,21)
    41
    100
    100
    100
    32.5
    57.1
        Week 32 Pre-infusion (n=60,63,63,126,39,21)
    8.3
    95.2
    100
    97.6
    10.3
    4.8
        Week 32 Post-infusion (n=60,63,59,122,38,22)
    35
    100
    100
    100
    26.3
    50
    Notes
    [66] - n = number of participants analyzed at the specified visit.
    [67] - n = number of participants analyzed at the specified visit.
    [68] - n = number of participants analyzed at the specified visit.
    [69] - n = number of participants analyzed at the specified visit.
    [70] - n = number of participants analyzed at the specified visit.
    [71] - n = number of participants analyzed at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants with CD19+ Absolute B Cell Counts Less than the Lower Limit of Normal (LLN) by Visit

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    End point title
    		 Percentage of Participants with CD19+ Absolute B Cell Counts Less than the Lower Limit of Normal (LLN) by Visit
    End point description
    CD19 is a cell surface molecule which assembles with the antigen receptor of B lymphocytes. It is a critical signal transduction molecule that regulates B lymphocyte development, activation, and differentiation. <LLN = 80 cells/uL.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 15, Week 4, 16, 32, 48, and by infusion (pre and post infusion) on Day 1, 15, Week 16, 32
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC Placebo-Mycophenolate Mofetil (MMF) Placebo-Euro Lupus (EL)
    Number of subjects analysed
    70 [72]
    73 [73]
    70 [74]
    141 [75]
    45 [76]
    27 [77]
    Units: Percentage of participants
    number (not applicable)
        Baseline (n=70,71,66,137,44,26)
    27.1
    36.6
    33.3
    35
    29.5
    23.1
        Day 15 (n=66,70,68,138,40,26)
    28.8
    100
    100
    100
    30
    26.9
        Week 4 (n=68,67,67,134,41,27)
    39.7
    100
    100
    100
    39
    40.7
        Week 16 (n=70,72,69,141,45,25)
    57.1
    100
    100
    100
    48.9
    72
        Week 32 (n=68,73,68,141,45,23)
    52.9
    97.3
    100
    98.6
    35.6
    87
        Week 48 (n=68,71,66,137,45,23)
    51.5
    97.2
    100
    98.5
    37.8
    78.3
        Day 1 Pre-infusion (n=70,71,67,138,44,26)
    27.1
    36.6
    32.8
    34.8
    29.5
    23.1
        Day 1 Post-infusion (n=70,69,68,137,43,27)
    55.7
    97.1
    100
    98.5
    53.5
    59.3
        Day 15 Pre-infusion (n=68,68,70,138,43,25)
    30.9
    100
    100
    100
    32.6
    28
        Day 15 Post-infusion (n=67,65,68,133,42,25)
    58.2
    100
    100
    100
    52.4
    68
        Week 16 Pre-infusion (n=67,66,66,132,43,24)
    56.7
    100
    100
    100
    48.8
    70.8
        Week 16 Post-infusion (n=61,66,66,132,40,21)
    80.3
    100
    100
    100
    72.5
    95.2
        Week 32 Pre-infusion (n=60,63,63,126,39,21)
    50
    98.4
    100
    99.2
    30.8
    85.7
        Week 32 Post-infusion (n=60,63,59,122,38,22)
    88.3
    100
    100
    100
    84.2
    95.5
    Notes
    [72] - n = number of participants analyzed at the specified visit.
    [73] - n = number of participants analyzed at the specified visit.
    [74] - n = number of participants analyzed at the specified visit.
    [75] - n = number of participants analyzed at the specified visit.
    [76] - n = number of participants analyzed at the specified visit.
    [77] - n = number of participants analyzed at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response

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    End point title
    		 Percentage of Participants Achieving a Major Clinical Response or a Partial Clinical Response
    End point description
    A major clinical response was defined as British Isles Lupus Assessment Group (BILAG) C scores or better at Week 24 without developing any new A or two new B scores up to Week 24 and maintenance of this response without developing a moderate or severe flare between Week 24 and Week 48. A partial clinical response was defined as BILAG C scores or better at Week 24 and maintaining this response without developing a flare for 16 consecutive weeks. The BILAG is an organ-specific 86-question assessment based on the principle of the doctor’s intent to treat, which requires an assessment of improved (1), the same (2), worse (3), or new (4) over the last month. Within each organ system, multiple manifestations and laboratory tests are combined into a single score for that organ. The resulting scores for each organ can be A through E, where A is very active disease, B is moderate activity, C is mild stable disease, D is resolved activity, and E indicates the organ was never involved.
    End point type
    Secondary
    End point timeframe
    Baseline and Weeks 1, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48
    End point values
    		 Placebo Ocrelizumab 400 mg Ocrelizumab 1000 mg OCR + SOC
    Number of subjects analysed
    0 [78]
    0 [79]
    0 [80]
    0 [81]
    Units: percentage of participants
        number (not applicable)
    Notes
    [78] - Due to early termination of the study, no secondary analyses were performed.
    [79] - Due to early termination of the study, no secondary analyses were performed.
    [80] - Due to early termination of the study, no secondary analyses were performed.
    [81] - Due to early termination of the study, no secondary analyses were performed.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were recorded from Screening until study termination.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    13.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matched to ocrelizumab infusion intravenously (IV) on Days 1 and 15, followed by placebo matched to ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or mycophenolate mofetil (MMF) 1 grams per day (g/day) in the first week increased to 3 g/day. Participants also received methylprednisolone 100 milligram (mg) infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of placebo. Participants also received oral prednisone at a starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Reporting group title
    Ocrelizumab 1000 mg
    Reporting group description
    		 Participants received 1000 mg ocrelizumab IV on Days 1 and 15, followed by 1000 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Reporting group title
    Ocrelizumab 400 mg
    Reporting group description
    		 Participants received 400 mg ocrelizumab IV on Days 1 and 15, followed by 400 mg ocrelizumab infusion IV on Week 16 and then every 16 weeks up to 48 weeks along with one of the two standard-of-care (SOC) immunosuppressant regimens at the discretion of the investigator. The SOC regimens were: Euro-Lupus (cyclophosphamide 500 mg every 2 weeks for 6 doses followed by azathioprine maintenance at 1-2 milligrams per kilogram per day [mg/kg/day]), or MMF 1 g/day in the first week increased to 3 g/day. Participants also received methylprednisolone 100 mg infusion IV or according to local guidelines, completed at least 30 minutes prior to each infusion of ocrelizumab. Participants also received oral prednisone at starting dose of 0.75 mg/kg/day with a maximum dose of 60 mg/day from Day 2. Beginning on Day 16 the doses were tapered and continued for 10 weeks to a target dose of 10 mg/day.

    Serious adverse events
    		 Placebo Ocrelizumab 1000 mg Ocrelizumab 400 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    36 / 125 (28.80%)
    38 / 127 (29.92%)
    52 / 126 (41.27%)
         number of deaths (all causes)
    6
    6
    3
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anogenital warts
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal adenoma
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cell carcinoma
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant hypertension
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion missed
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gestational hypertension
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Polyserositis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervical dysplasia
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ovarian mass
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Suicide attempt
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatine increased
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Weight increased
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thermal burn
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Pleuropericarditis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cerebral infarction
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lupus encephalitis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vasculitis cerebral
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Agranulocytosis
         subjects affected / exposed
    0 / 125 (0.00%)
    3 / 127 (2.36%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    3 / 126 (2.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia of chronic disease
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Antiphospholipid syndrome
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Febrile neutropenia
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 125 (0.80%)
    5 / 127 (3.94%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 1
    3 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal ulcer
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatitis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Angioedema
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Lupus nephritis
         subjects affected / exposed
    2 / 125 (1.60%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal disorder
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 125 (1.60%)
    1 / 127 (0.79%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure acute
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Renal failure chronic
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tubulointerstitial nephritis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary bladder haemorrhage
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscle contracture
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    3 / 125 (2.40%)
    2 / 127 (1.57%)
    3 / 126 (2.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess limb
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis bacterial
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 125 (0.80%)
    2 / 127 (1.57%)
    5 / 126 (3.97%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
    2 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear infection
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enteritis infectious
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    3 / 125 (2.40%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma infection
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes virus infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 125 (0.00%)
    3 / 127 (2.36%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster disseminated
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Impetigo
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    infection
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Laryngitis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Legionella infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neurocryptococcosis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 125 (1.60%)
    8 / 127 (6.30%)
    4 / 126 (3.17%)
         occurrences causally related to treatment / all
    1 / 2
    4 / 8
    2 / 5
         deaths causally related to treatment / all
    0 / 1
    2 / 3
    0 / 0
    Pneumonia cytomegaloviral
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyoderma
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salmonella bacteraemia
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salmonella sepsis
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 127 (0.79%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Skin infection
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    1 / 126 (0.79%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Strongyloidiasis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    1 / 125 (0.80%)
    0 / 127 (0.00%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 125 (0.00%)
    2 / 127 (1.57%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 125 (0.00%)
    2 / 127 (1.57%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 125 (0.00%)
    1 / 127 (0.79%)
    0 / 126 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    1 / 125 (0.80%)
    2 / 127 (1.57%)
    4 / 126 (3.17%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus
         subjects affected / exposed
    0 / 125 (0.00%)
    0 / 127 (0.00%)
    2 / 126 (1.59%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Ocrelizumab 1000 mg Ocrelizumab 400 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    96 / 125 (76.80%)
    91 / 127 (71.65%)
    101 / 126 (80.16%)
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    11 / 125 (8.80%)
    17 / 127 (13.39%)
    14 / 126 (11.11%)
         occurrences all number
    12
    19
    18
    Vascular disorders
    Hypertension
         subjects affected / exposed
    7 / 125 (5.60%)
    12 / 127 (9.45%)
    12 / 126 (9.52%)
         occurrences all number
    8
    15
    19
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    9 / 125 (7.20%)
    5 / 127 (3.94%)
    6 / 126 (4.76%)
         occurrences all number
    9
    6
    6
    Headache
         subjects affected / exposed
    11 / 125 (8.80%)
    11 / 127 (8.66%)
    15 / 126 (11.90%)
         occurrences all number
    18
    12
    21
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 125 (4.00%)
    7 / 127 (5.51%)
    13 / 126 (10.32%)
         occurrences all number
    5
    7
    17
    Leukopenia
         subjects affected / exposed
    7 / 125 (5.60%)
    12 / 127 (9.45%)
    18 / 126 (14.29%)
         occurrences all number
    11
    17
    24
    Neutropenia
         subjects affected / exposed
    6 / 125 (4.80%)
    7 / 127 (5.51%)
    15 / 126 (11.90%)
         occurrences all number
    7
    10
    27
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    8 / 125 (6.40%)
    4 / 127 (3.15%)
    2 / 126 (1.59%)
         occurrences all number
    9
    4
    5
    Pyrexia
         subjects affected / exposed
    1 / 125 (0.80%)
    2 / 127 (1.57%)
    7 / 126 (5.56%)
         occurrences all number
    1
    3
    7
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 125 (2.40%)
    7 / 127 (5.51%)
    5 / 126 (3.97%)
         occurrences all number
    3
    8
    5
    Diarrhoea
         subjects affected / exposed
    22 / 125 (17.60%)
    32 / 127 (25.20%)
    26 / 126 (20.63%)
         occurrences all number
    29
    36
    35
    Dyspepsia
         subjects affected / exposed
    4 / 125 (3.20%)
    3 / 127 (2.36%)
    9 / 126 (7.14%)
         occurrences all number
    5
    3
    10
    Gastritis
         subjects affected / exposed
    2 / 125 (1.60%)
    2 / 127 (1.57%)
    11 / 126 (8.73%)
         occurrences all number
    2
    3
    15
    Nausea
         subjects affected / exposed
    7 / 125 (5.60%)
    4 / 127 (3.15%)
    13 / 126 (10.32%)
         occurrences all number
    7
    5
    16
    Vomiting
         subjects affected / exposed
    7 / 125 (5.60%)
    4 / 127 (3.15%)
    11 / 126 (8.73%)
         occurrences all number
    7
    4
    11
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 125 (5.60%)
    4 / 127 (3.15%)
    11 / 126 (8.73%)
         occurrences all number
    8
    5
    12
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    8 / 125 (6.40%)
    1 / 127 (0.79%)
    3 / 126 (2.38%)
         occurrences all number
    8
    1
    3
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    3 / 125 (2.40%)
    7 / 127 (5.51%)
    7 / 126 (5.56%)
         occurrences all number
    4
    7
    7
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 125 (4.00%)
    6 / 127 (4.72%)
    7 / 126 (5.56%)
         occurrences all number
    5
    8
    9
    Back pain
         subjects affected / exposed
    6 / 125 (4.80%)
    8 / 127 (6.30%)
    6 / 126 (4.76%)
         occurrences all number
    6
    8
    8
    Muscle spasms
         subjects affected / exposed
    7 / 125 (5.60%)
    4 / 127 (3.15%)
    8 / 126 (6.35%)
         occurrences all number
    7
    4
    8
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    10 / 125 (8.00%)
    10 / 127 (7.87%)
    14 / 126 (11.11%)
         occurrences all number
    16
    12
    17
    Gastroenteritis
         subjects affected / exposed
    10 / 125 (8.00%)
    4 / 127 (3.15%)
    7 / 126 (5.56%)
         occurrences all number
    11
    4
    10
    Herpes zoster
         subjects affected / exposed
    6 / 125 (4.80%)
    9 / 127 (7.09%)
    8 / 126 (6.35%)
         occurrences all number
    6
    11
    9
    Nasopharyngitis
         subjects affected / exposed
    16 / 125 (12.80%)
    13 / 127 (10.24%)
    17 / 126 (13.49%)
         occurrences all number
    23
    20
    24
    Oral candidiasis
         subjects affected / exposed
    1 / 125 (0.80%)
    1 / 127 (0.79%)
    7 / 126 (5.56%)
         occurrences all number
    1
    1
    10
    Pharyngitis
         subjects affected / exposed
    4 / 125 (3.20%)
    7 / 127 (5.51%)
    13 / 126 (10.32%)
         occurrences all number
    4
    7
    13
    Sinusitis
         subjects affected / exposed
    3 / 125 (2.40%)
    7 / 127 (5.51%)
    3 / 126 (2.38%)
         occurrences all number
    4
    12
    5
    Upper respiratory tract infection
         subjects affected / exposed
    19 / 125 (15.20%)
    23 / 127 (18.11%)
    22 / 126 (17.46%)
         occurrences all number
    28
    43
    42
    Urinary tract infection
         subjects affected / exposed
    13 / 125 (10.40%)
    18 / 127 (14.17%)
    24 / 126 (19.05%)
         occurrences all number
    13
    35
    43
    Metabolism and nutrition disorders
    Dyslipidaemia
         subjects affected / exposed
    11 / 125 (8.80%)
    2 / 127 (1.57%)
    5 / 126 (3.97%)
         occurrences all number
    14
    2
    5
    Hypokalaemia
         subjects affected / exposed
    9 / 125 (7.20%)
    4 / 127 (3.15%)
    9 / 126 (7.14%)
         occurrences all number
    12
    4
    16

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Oct 2008
    This amendment was made to clarify the flexibility of protocol in applying the regional participant management strategies using SOC regimens for treatment of LN and to ensure participant safety during administration of immunosupressive therapies, to clarify the use of corticosteroids during the trial and to clarify screening procedures and use of medications during screening to help recruitment.
    04 Jan 2010
    On 19th October 2009 this Study (WA20500/ACT4072g) was stopped due to an imbalance of serious and opportunistic infections in the ocrelizumab treated patients versus the placebo arm. This was identified through the ongoing safety review of participant data and following interactions with both the US FDA and the BELONG Data and Safety Monitoring Board (DSMB). There was no further study drug infusions either blinded or open label in the Double Blind Treatment Period, Study Extension Treatment Period or Open Label Period. Patients who received ocrelizumab entered the Safety Follow Up period after completing the withdrawal visit and followed the Safety Follow Up assessments and Schedule. Participants who received placebo were not required to take part in the Safety Follow Up and were discontinued from the study.
    28 Sep 2012
    Safety data from the participants ongoing in the study were evaluated and the sponsor decided to terminate further Safety follow-up in participants treated with ocrelizumab.

    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.
    The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated participants versus placebo-treated participants. Only 139 of the 381 participants randomized completed the 48 week treatment period.
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    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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