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    Clinical Trial Results:
    A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Obinutuzumab in Patients with ISN/RPS 2003 Class III or IV Lupus Nephritis

    Summary
    EudraCT number
    		 2015-002022-39
    Trial protocol
    		 ES   FR   IT  
    Global end of trial date
    02 Aug 2023

    Results information
    Results version number
    		 v4(current)
    This version publication date
    16 Aug 2024
    First version publication date
    31 Jan 2020
    Other versions
    		 v1 , v2 , v3
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    WA29748
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02550652
    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
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
    Scientific contact
    F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, 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
    02 Aug 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Aug 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This Phase II study compared the efficacy and safety of obinutuzumab plus mycophenolate mofetil (MMF)/mycophenolic acid (MPA) with placebo plus MMF/MPA in participants with proliferative lupus nephritis (LN).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 Antimalarials Angiotensin-converting Enzyme (ACE) inhibitors Angiotensin-receptor Blockers (ARB) Glucocorticoid Taper
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Nov 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 18 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 27
    Country: Number of subjects enrolled
    Brazil: 8
    Country: Number of subjects enrolled
    Colombia: 19
    Country: Number of subjects enrolled
    Costa Rica: 2
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Israel: 4
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Mexico: 15
    Country: Number of subjects enrolled
    Panama: 1
    Country: Number of subjects enrolled
    Peru: 13
    Country: Number of subjects enrolled
    United States: 15
    Worldwide total number of subjects
    125
    EEA total number of subjects
    21
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    125
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled at approximately 60 centers in North America, South America, Europe, and Asia.

    Pre-assignment
    Screening details
    		 A total of 126 patients were enrolled in the study however one patient randomized to obinutuzumab did not receive study treatment due to a positive pregnancy test, but prior to the first study drug infusion; therefore a total of 125 patients are included in the analysis.

    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
    		 OBINUTUZUMAB 1000MG and MMF
    Arm description
    		 Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mycophenolate Mofetil/Mycophenolic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MMF/MPA will be administered as per schedule specified in the respective arm.

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    Gazyva, GA101, RO5072759
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab will be administered as per schedule specified in the respective arm.

    Arm title
    		 PLACEBO and MMF
    Arm description
    		 Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Placebo matching to obinutuzumab will be administered as per schedule specified in the respective arm.

    Investigational medicinal product name
    Mycophenolate Mofetil/Mycophenolic Acid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    MMF/MPA will be administered as per schedule specified in the respective arm.

    Number of subjects in period 1
    		OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Started
    63
    62
    Completed
    55
    44
    Not completed
    8
    18
         Consent withdrawn by subject
    4
    7
         Physician decision
    -
    2
         Death
    1
    4
         Add. therapies that reduce perip. B cell count
    -
    2
         Post Trial Access
    1
    -
         Lost to follow-up
    1
    3
         Lack of efficacy
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    OBINUTUZUMAB 1000MG and MMF
    Reporting group description
    		 Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Reporting group title
    PLACEBO and MMF
    Reporting group description
    		 Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Reporting group values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF Total
    Number of subjects
    		 63 62 125
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 63 62 125
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 33.1 ( 9.8 ) 31.9 ( 10.1 ) -
    Sex: Female, Male
    Units:
        Female
    		 55 51 106
        Male
    		 8 11 19
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic Or Latino
    		 42 49 91
        Not Hispanic Or Latino
    		 20 12 32
        Not Stated
    		 1 0 1
        Unknown
    		 0 1 1
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 11 17 28
        Asian
    		 3 2 5
        Black or African American
    		 6 5 11
        Multiple
    		 1 0 1
        Native Hawaiian or other Pacific Islande
    		 1 0 1
        Unknown
    		 13 12 25
        White
    		 28 26 54
    Subject analysis sets

    Subject analysis set title
    Obinutuzumab
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis set title
    Obinutuzumab
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis sets values
    		 Obinutuzumab Placebo Obinutuzumab Placebo
    Number of subjects
    63
    62
    64
    61
    Age categorical
    Units: Subjects
        In utero
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
        Adults (18-64 years)
    63
    62
    64
    61
        From 65-84 years
    0
    0
    0
    0
        85 years and over
    0
    0
    0
    0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    33.1 ( 9.8 )
    31.9 ( 10.1 )
    33.0 ( 9.8 )
    32.0 ( 10.1 )
    Sex: Female, Male
    Units:
        Female
    55
    51
    56
    50
        Male
    8
    11
    8
    11
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic Or Latino
    42
    49
    43
    48
        Not Hispanic Or Latino
    20
    12
    20
    12
        Not Stated
    1
    0
    1
    0
        Unknown
    0
    1
    0
    1
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    11
    17
    11
    17
        Asian
    3
    2
    3
    2
        Black or African American
    6
    5
    6
    5
        Multiple
    1
    0
    1
    0
        Native Hawaiian or other Pacific Islande
    1
    0
    1
    0
        Unknown
    13
    12
    13
    12
        White
    28
    26
    29
    25

    End points

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    End points reporting groups
    Reporting group title
    OBINUTUZUMAB 1000MG and MMF
    Reporting group description
    		 Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Reporting group title
    PLACEBO and MMF
    Reporting group description
    		 Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis set title
    Obinutuzumab
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis set title
    Obinutuzumab
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants will receive obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Participants will receive placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose will be up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, may use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants may receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants will receive 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Primary: Percentage of Participants who Achieve Protocol Defined Complete Renal Response (CRR)

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    End point title
    		 Percentage of Participants who Achieve Protocol Defined Complete Renal Response (CRR)
    End point description
    Percentage of participants with normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN range of central laboratory values.
    End point type
    Primary
    End point timeframe
    From baseline to Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    22
    14
    Units: Percentage of participants
        number (not applicable)
    34.9
    22.6
    Statistical analysis title
    		 Protocol Defined CRR (80% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1145 [1]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    12.3
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 2.1
         upper limit
    		 22.6
    Notes
    [1] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 Protocol Defined CRR (95% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1145 [2]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    12.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 28.1
    Notes
    [2] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Percentage of Participants who Achieve Protocol Defined Overall Response (OR)

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    End point title
    		 Percentage of Participants who Achieve Protocol Defined Overall Response (OR)
    End point description
    OR includes both CRR and partial renal response (PRR). CRR as defined in primary outcome measure. PRR defined as 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then urine protein:creatinine ratio of <1.0. 2. If baseline protein:creatinine ratio is > 3.0, then urine protein:creatinine ratio of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF.
    End point type
    Secondary
    End point timeframe
    From baseline to Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    35
    22
    Units: Percentage of participants
        number (not applicable)
    55.6
    35.5
    Statistical analysis title
    		 Protocol defined Overall Response (80% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0246 [3]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    20.1
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 8.9
         upper limit
    		 31.3
    Notes
    [3] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 Protocol defined Overall Response (95% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    57
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0246 [4]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    20.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3
         upper limit
    		 37.2
    Notes
    [4] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Time to OR Over 52 Weeks

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    End point title
    		 Time to OR Over 52 Weeks
    End point description
    OR includes both CRR and partial renal response (PRR). CRR as defined in the primary outcome measure above. PRR defined as 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then urine protein:creatinine ratio of <1.0. 2. If baseline protein:creatinine ratio is > 3.0, then urine protein:creatinine ratio of <3.0, serum creatinine ≤15% above baseline value, and no urinary red cell casts and either RBCs/HPF ≤50% above baseline or <10 RBCs/HPF. Percentage of Participants with response at various time points were measured using Kaplan Meier method.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) to Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    63
    62
    Units: Percentage of participants
    number (not applicable)
        Week 12 (n=55, 59)
    87.3
    95.2
        Week 24 (n=33, 37)
    52.4
    59.7
        Week 36 (n=21, 29)
    33.3
    46.8
        Week 52 (n=14, 21)
    22.2
    33.9
    Statistical analysis title
    		 Time to ORR Over 52 Weeks
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0744
    Method
    		 Logrank
    Confidence interval

    Secondary: Percentage of Participants who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52

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    End point title
    		 Percentage of Participants who Achieve Protocol Defined Partial Renal Response (PRR) at Week 52
    End point description
    PRR defined as serum creatinine ≤15% above baseline value, no urinary red cell casts and either RBCs/HPF ≤ 50% above baseline or < 10 RBCs/HPF, 50% improvement in urine protein:creatinine ratio, with one of following conditions met: 1. If baseline urine protein:creatinine ratio is ≤ 3.0, then a urine protein:creatinine ratio of < 1.0. 2. If baseline protein:creatinine ratio is > 3.0, then a urine protein:creatinine ratio of < 3.0.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    35
    21
    Units: Percentage of participants
        number (not applicable)
    55.6
    33.9
    Statistical analysis title
    		 Protocol Defined PRR (95% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.015 [5]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    21.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.7
         upper limit
    		 38.7
    Notes
    [5] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 Protocol Defined PRR (80% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.015 [6]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in % of Participants
    Point estimate
    21.7
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 10.6
         upper limit
    		 32.8
    Notes
    [6] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Percentage of Participants who Achieve Protocol Defined CRR at Week 24

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    End point title
    		 Percentage of Participants who Achieve Protocol Defined CRR at Week 24
    End point description
    CRR defined as normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 red blood cells (RBCs)/high-power field (HPF) and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the upper limit of normal (ULN) range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    16
    17
    Units: Percentage of participants
        number (not applicable)
    25.4
    27.4
    Statistical analysis title
    		 Protocol Defined CRR (80% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8461 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    -2
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -12.1
         upper limit
    		 8.1
    Notes
    [7] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 Protocol Defined CRR (95% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.8461 [8]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.5
         upper limit
    		 13.4
    Notes
    [8] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Time to CRR Over 52 Weeks

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    End point title
    		 Time to CRR Over 52 Weeks
    End point description
    CRR included normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts) and urinary protein to creatinine ratio < 0.5. Normalization of serum creatinine is defined as serum creatinine ≤ the ULN range of central laboratory values if baseline serum creatinine is above the ULN or serum creatinine ≤ 15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values. Percentage of participants with response at various time points were measured using Kaplan Meier method.
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    63
    62
    Units: Percentage of participants
    number (not applicable)
        Week 12 (n-61,60)
    96.8
    96.8
        Week 24 (n=47,48)
    74.6
    77.4
        Week 36 (n=38,38)
    60.3
    61.3
        Week 52 (n=27,33)
    42.9
    53.2
    Statistical analysis title
    		 Time to Protocol Defined CRR
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.353
    Method
    		 Logrank
    Confidence interval

    Secondary: Change From Baseline in Complement component 3 (C3) Levels

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    End point title
    		 Change From Baseline in Complement component 3 (C3) Levels
    End point description
    Complement C3 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    63
    62
    Units: g/L
        arithmetic mean (standard deviation)
    0.311 ( 0.302 )
    0.106 ( 0.273 )
    Statistical analysis title
    		 C3
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0004 [9]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.178
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.081
         upper limit
    		 0.275
    Notes
    [9] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 C3 (80% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0004 [10]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.178
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.115
         upper limit
    		 0.241
    Notes
    [10] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Levels

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    End point title
    		 Change From Baseline in Anti-Double Stranded Deoxyribonucleic Acid (Anti-dsDNA) Levels
    End point description
    Anti-dsDNA antibodies are a group of anti-nuclear autoantibodies targeting double stranded DNA.
    End point type
    Secondary
    End point timeframe
    From baseline to Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    63
    62
    Units: log anti-dsDNA levels
        arithmetic mean (standard deviation)
    -0.810 ( 1.054 )
    -0.076 ( 1.103 )
    Statistical analysis title
    		 Anti-Ds DNA (80% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [11]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.81
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -1.019
         upper limit
    		 -0.602
    Notes
    [11] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 Anti-Ds DNA
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [12]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.13
         upper limit
    		 -0.491
    Notes
    [12] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Change From Baseline in C4 Levels

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    End point title
    		 Change From Baseline in C4 Levels
    End point description
    Complement C4 is a blood test that reflects activation of complement pathway associated with immune deposition in certain autoimmune diseases.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 52
    End point values
    		 OBINUTUZUMAB 1000MG and MMF PLACEBO and MMF
    Number of subjects analysed
    63
    62
    Units: g/L
        arithmetic mean (standard deviation)
    0.101 ( 0.117 )
    0.004 ( 0.164 )
    Statistical analysis title
    		 C4 (80% CI)
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [13]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.088
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.065
         upper limit
    		 0.112
    Notes
    [13] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 C4
    Comparison groups
    OBINUTUZUMAB 1000MG and MMF v PLACEBO and MMF
    Number of subjects included in analysis
    125
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [14]
    Method
    		 ANCOVA
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.088
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.052
         upper limit
    		 0.124
    Notes
    [14] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Percentage of Participants who Achieve Protocol Defined Modified CRR (mCRR1)

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    End point title
    		 Percentage of Participants who Achieve Protocol Defined Modified CRR (mCRR1)
    End point description
    mCRR1 has got two components only, i.e. serum Creatinine and urinary protein to creatinine ratio. mCRR1 is defined by attainment of normalization of serum creatinine as evidenced by 1.) serum creatinine ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is above the ULN or serum creatinine ≤15% above baseline and ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine ≤ the ULN range of central laboratory values and 2.) Urinary protein to creatinine ratio <0.5.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Obinutuzumab Placebo
    Number of subjects analysed
    25
    16
    Units: Percentage of participants
        number (not applicable)
    39.7
    25.8
    Statistical analysis title
    		 mCRR1 (95% CI)
    Comparison groups
    Placebo v Obinutuzumab
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.09 [15]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Proportion Difference
    Point estimate
    13.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.4
         upper limit
    		 30.1
    Notes
    [15] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 mCRR1 (80% CI)
    Comparison groups
    Obinutuzumab v Placebo
    Number of subjects included in analysis
    41
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.09 [16]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    13.9
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 3.2
         upper limit
    		 24.5
    Notes
    [16] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Percentage of Participants who Achieve Protocol Defined Third mCRR (mCRR3)

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    End point title
    		 Percentage of Participants who Achieve Protocol Defined Third mCRR (mCRR3)
    End point description
    mCRR3 is defined by normalization of serum creatine as evidenced by serum creatinine ≤ the ULN range of central laboratory values and urinary protein to creatinine ratio < 0.5.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Obinutuzumab Placebo
    Number of subjects analysed
    29
    24
    Units: Percentage of participants
        number (not applicable)
    46.0
    38.7
    Statistical analysis title
    		 mCRR3 (80% CI)
    Comparison groups
    Obinutuzumab v Placebo
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3726 [17]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    7.3
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -4
         upper limit
    		 18.6
    Notes
    [17] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 mCRR3 (95% CI)
    Comparison groups
    Obinutuzumab v Placebo
    Number of subjects included in analysis
    53
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.3726 [18]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    7.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10
         upper limit
    		 24.6
    Notes
    [18] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Percentage of Participants who Achieve Protocol Defined Second mCRR (mCRR2)

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    End point title
    		 Percentage of Participants who Achieve Protocol Defined Second mCRR (mCRR2)
    End point description
    mCRR2 is defined by normalization of serum creatinine, inactive urinary sediment (as evidenced by < 10 RBCs/HPF and the absence of red cell casts), and urinary protein to creatinine ratio <0.5. Normalization of serum creatinine as evidenced by the following: Serum creatinine ≤15% above baseline if baseline (Day 1) serum creatinine is above the normal range of the central laboratory values or ≤ the ULN range of central laboratory values if baseline (Day 1) serum creatinine is ≤ the ULN range of central laboratory values.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Obinutuzumab Placebo
    Number of subjects analysed
    28
    21
    Units: Percentage of participants
        number (not applicable)
    44.4
    33.9
    Statistical analysis title
    		 mCRR2 (80% CI)
    Comparison groups
    Obinutuzumab v Placebo
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1838 [19]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    10.6
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 -0.5
         upper limit
    		 21.7
    Notes
    [19] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.
    Statistical analysis title
    		 mCRR2 (95% CI)
    Comparison groups
    Obinutuzumab v Placebo
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1838 [20]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Percentage of Participants
    Point estimate
    10.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.4
         upper limit
    		 27.6
    Notes
    [20] - Stratified by race (Afro Caribbean/African American vs. Others) and region (US vs. non-US sites). Statistically significant at pre-specified alpha of 20%.

    Secondary: Percentage of Participants With Adverse Events (AEs)

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    End point title
    		 Percentage of Participants With Adverse Events (AEs)
    End point description
    An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, Serious Adverse Events (SAEs), Infections and Serious infections. The AEs reported do not include events after the receipt of rescue medications.
    End point type
    Secondary
    End point timeframe
    From baseline to approximately 7 years and 8 months
    End point values
    		 Obinutuzumab Placebo
    Number of subjects analysed
    64
    61
    Units: Percentage of participants
    number (not applicable)
        Adverse Events (n=58,54)
    90.6
    88.5
        Grade 3 AEs (n=19,15)
    29.7
    24.6
        Grade 4 AEs (n=6,7)
    9.4
    11.5
        Grade 5 AEs (n=1,2)
    1.6
    3.3
        Serious Adverse Events (n=16,17)
    25.0
    27.9
        Infections (n=48,38)
    76.6
    62.3
        Serious infections (n=5,10)
    7.8
    16.4
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia

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    End point title
    		 Percentage of Participants with Adverse Events of Special Interest: Infusion Related Reactions, Grade 3 or Higher Infections, Drug-related Neutropenia and Drug-related Thrombocytopenia
    End point description
    Infusion related reaction is defined as any event reported within 24 hours of infusion and thought to be causally related to the investigational agent by the investigator. Grade 3 or higher infections include all events of Grade 3 to 5 under the SOC of infections and infestations. Drug-related neutropenia is defined as events in the Roche AE Grouped Term (AEGT) “Neutropenia and associated complications” and thought to be causally related to the investigational agent by the investigator. Drug-related thrombocytopenia is defined as events in the Standard MedDRA Query (SMQ) “Haematopoietic Thrombocytopenia narrow” and thought to be causally related to the investigational agent by the investigator.
    End point type
    Secondary
    End point timeframe
    From baseline to approximately 7 years and 8 months
    End point values
    		 Obinutuzumab Placebo
    Number of subjects analysed
    64
    61
    Units: Percentage of participants
    number (not applicable)
        Infusion Related Reactions (n=10,6)
    15.6
    9.8
        Grade 3 or Higher Infections (n=4,11)
    6.3
    18.0
        Drug-related Neutropenia (n=3,2)
    4.7
    3.3
        Drug-related Thrombocytopenia (n=0,0)
    0
    0
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab

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    End point title
    		 Percentage of Participants With Anti-Drug Antibody (ADA) to Obinutuzumab [21]
    End point description
    Antibodies are a blood protein produced in response to and counteracting a specific antigen.
    End point type
    Secondary
    End point timeframe
    From baseline to approximately 7 years and 8 months
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As the end point is analyzing obinutuzumab, there is nothing to report for the placebo arm.
    End point values
    		 OBINUTUZUMAB 1000MG and MMF
    Number of subjects analysed
    7
    Units: Percentage of participants
        number (not applicable)
    11.11
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels

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    End point title
    		 Percent Change From Baseline in Circulating CD19-Positive B-Cell Levels
    End point description
    CD19+ B cell is a B-lymphocyte with a transmembrane protein that is encoded by the gene CD19. 9999999 = The standard deviation could not be derived from the data of 1 participant. 9999999 = No participants were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, Week 4, Week 12, Week 24, Week 52, Week 104, B Cell Follow-Up (Bcfu) at months 6, 12, 18, 24, 30, 36, 42 and 48
    End point values
    		 Obinutuzumab Placebo
    Number of subjects analysed
    63
    62
    Units: cells/uL
    arithmetic mean (standard deviation)
        Baseline (n=63, 62)
    327.902 ( 330.562 )
    353.499 ( 454.165 )
        Week 2 (n=39, 42)
    -97.469 ( 12.899 )
    39.293 ( 145.247 )
        Week 4 (n=45, 36)
    -98.777 ( 5.235 )
    -5.186 ( 78.469 )
        Week 12 (n=41, 45)
    -97.045 ( 15.506 )
    0.661 ( 134.421 )
        Week 24 (n=42, 37)
    -96.628 ( 10.207 )
    -11.446 ( 86.793 )
        Week 52 (n=39, 42)
    -98.620 ( 5.677 )
    37.695 ( 220.857 )
        Week 104 (n=5,2)
    77.123 ( 380.111 )
    -76.055 ( 31.519 )
        Bcfu month 6 (n=13, 5)
    105.043 ( 402.281 )
    -73.889 ( 19.755 )
        Bcfu month 12 (n=5, 2)
    77.123 ( 380.111 )
    -76.055 ( 31.519 )
        Bcfu month 18 (n=3, 1)
    -83.159 ( 16.701 )
    -11.418 ( 9999999 )
        Bcfu month 24 (n=2, 0)
    -93.603 ( 8.836 )
    9999999 ( 9999999 )
        Bcfu month 30 (n=3, 0)
    -59.950 ( 50.807 )
    9999999 ( 9999999 )
        Bcfu month 36 (n=2, 0)
    -99.163 ( 0.973 )
    9999999 ( 9999999 )
        Bcfu month 42 (n=1, 0)
    -99.084 ( 9999999 )
    9999999 ( 9999999 )
        Bcfu month 48 (n=1, 0)
    -99.851 ( 99999999 )
    9999999 ( 9999999 )
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab

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    End point title
    		 Maximum Observed Plasma Concentration (Cmax) of Obinutuzumab [22]
    End point description
    End point type
    Secondary
    End point timeframe
    Week 0, Week 24, Week 52
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As the end point is analyzing obinutuzumab, there is nothing to report for the placebo arm.
    End point values
    		 OBINUTUZUMAB 1000MG and MMF
    Number of subjects analysed
    63
    Units: ug/mL
    arithmetic mean (standard deviation)
        Week 0-24
    559 ( 112 )
        Week 24-52
    605 ( 115 )
        Week 0-52
    605 ( 115 )
    No statistical analyses for this end point

    Secondary: Systemic Clearance of Obinutuzumab

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    End point title
    		 Systemic Clearance of Obinutuzumab [23]
    End point description
    End point type
    Secondary
    End point timeframe
    Day 0, Week 24, Week 52
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As the end point is analyzing obinutuzumab, there is nothing to report for the placebo arm.
    End point values
    		 OBINUTUZUMAB 1000MG and MMF
    Number of subjects analysed
    63
    Units: L/day
    arithmetic mean (standard deviation)
        Day 0
    0.255 ( 0.136 )
        Week 24
    0.147 ( 0.0564 )
        Week 52
    0.137 ( 0.0535 )
    No statistical analyses for this end point

    Secondary: Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab

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    End point title
    		 Area Under the Plasma Concentration Versus Time Curve (AUC) of Obinutuzumab [24]
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to Week 52
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As the end point is analyzing obinutuzumab, there is nothing to report for the placebo arm.
    End point values
    		 OBINUTUZUMAB 1000MG and MMF
    Number of subjects analysed
    63
    Units: ug/mL*day
    arithmetic mean (standard deviation)
        Week 0-24
    10595 ( 4016 )
        Week 24-52
    15811 ( 5543 )
        Week 0-52
    26406 ( 9027 )
    No statistical analyses for this end point

    Secondary: Terminal Plasma Half-Life (t1/2) of Obinutuzumab

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    End point title
    		 Terminal Plasma Half-Life (t1/2) of Obinutuzumab
    End point description
    End point type
    Secondary
    End point timeframe
    Day 0, Week 24, Week 52
    End point values
    		 Obinutuzumab
    Number of subjects analysed
    64
    Units: day
    arithmetic mean (standard deviation)
        Day 0
    13.1 ( 3.7 )
        Week 24
    20.5 ( 5.6 )
        Week 52
    22.1 ( 6.7 )
    No statistical analyses for this end point

    Secondary: Volume of Distribution Under Steady State (Vss) of Obinutuzumab

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    End point title
    		 Volume of Distribution Under Steady State (Vss) of Obinutuzumab [25]
    End point description
    End point type
    Secondary
    End point timeframe
    Day 0, Week 24, Week 52
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: As the end point is analyzing obinutuzumab, there is nothing to report for the placebo arm.
    End point values
    		 OBINUTUZUMAB 1000MG and MMF
    Number of subjects analysed
    63
    Units: Litre (L)
    arithmetic mean (standard deviation)
        Day 0
    3.67 ( 0.591 )
        Week 24
    3.67 ( 0.591 )
        Week 52
    3.67 ( 0.591 )
    No statistical analyses for this end point

    Secondary: Change from Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score

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    End point title
    		 Change from Baseline of Participant's Global Assessment of Disease Activity Visual Analog Scale (VAS) Score
    End point description
    Each VAS had a range from 0-100 with higher scores indicating greater symptom impact on global health status.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1), Weeks 4, 12, 24, 36, 52
    End point values
    		 Obinutuzumab Placebo
    Number of subjects analysed
    63
    62
    Units: score on scale
    arithmetic mean (standard deviation)
        Baseline
    41.3 ( 25.59 )
    39.4 ( 24.76 )
        Week 4
    -14.4 ( 18.28 )
    -8.7 ( 22.69 )
        Week 12
    -19.9 ( 25.07 )
    -11.6 ( 25.22 )
        Week 24
    -25.0 ( 25.17 )
    -20.8 ( 24.74 )
        Week 36
    -24.8 ( 25.71 )
    -19.6 ( 25.04 )
        Week 52
    -25.4 ( 26.49 )
    -23.3 ( 25.76 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From baseline to approximately 7 years and 8 months
    Adverse event reporting additional description
    The safety population was defined as all participants who have received any amount of study medication
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    PLACEBO + MMF
    Reporting group description
    		 Participants received placebo matching to obinutuzumab IV infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 g/day (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Reporting group title
    OBINUTUZUMAB 1000MG + MMF
    Reporting group description
    		 Participants received obinutuzumab 1000 milligrams (mg) intravenous (IV) infusion on Days 1, 15, 168, and 182 along with MMF/MPA at a starting dose of 1500 mg/day (or equivalent) administered orally in 2 or 3 divided doses. MMF/MPA dose was up titrated to a target dose of 2.0 - 2.5 grams per day (g/day) (or equivalent). Investigators, at their discretion, could use MPA as a substitute for MMF, with a 360 mg dose being equivalent to a 500 mg dose of MMF. During screening or at randomization, if clinically indicated, participants could receive 1000 mg methylprednisolone IV once daily for up to 3 days to treat underlying LN clinical activity. Participants received 0.5 mg/kg oral prednisone, tapering this prednisone dose, per protocol, starting on Day 16 and reducing the prednisone dosage to 7.5 mg/day by Week 12.

    Serious adverse events
    		 PLACEBO + MMF OBINUTUZUMAB 1000MG + MMF
    Total subjects affected by serious adverse events
         subjects affected / exposed
    18 / 61 (29.51%)
    17 / 64 (26.56%)
         number of deaths (all causes)
    4
    1
         number of deaths resulting from adverse events
    2
    0
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SHOCK HAEMORRHAGIC
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SUPERFICIAL VEIN THROMBOSIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    ABORTION SPONTANEOUS
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    PYREXIA
         subjects affected / exposed
    1 / 61 (1.64%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    GENERAL PHYSICAL HEALTH DETERIORATION
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DEATH
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    ASTHMA
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY FAILURE
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PULMONARY ALVEOLAR HAEMORRHAGE
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PLEURITIC PAIN
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Psychiatric disorders
    PSYCHOTIC DISORDER
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    WEIGHT INCREASED
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INFLUENZA A VIRUS TEST POSITIVE
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    ROAD TRAFFIC ACCIDENT
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LUMBAR VERTEBRAL FRACTURE
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    CARDIAC FAILURE
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    EPILEPSY
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEADACHE
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    IDIOPATHIC INTRACRANIAL HYPERTENSION
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HEMIPARESIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEIZURE
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MYELITIS TRANSVERSE
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    THROMBOCYTOPENIA
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    LEUKOPENIA
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    INTESTINAL PERFORATION
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UPPER GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    OESOPHAGEAL FISTULA
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    INTUSSUSCEPTION
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ABDOMINAL PAIN
         subjects affected / exposed
    0 / 61 (0.00%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    HEPATITIS ACUTE
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CHOLELITHIASIS
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    LUPUS NEPHRITIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RENAL FAILURE
         subjects affected / exposed
    2 / 61 (3.28%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    RENAL IMPAIRMENT
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    NEPHROPATHY TOXIC
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ARTHRITIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SYSTEMIC LUPUS ERYTHEMATOSUS
         subjects affected / exposed
    2 / 61 (3.28%)
    2 / 64 (3.13%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Infections and infestations
    CYTOMEGALOVIRUS CHORIORETINITIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    BRONCHIOLITIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    CYTOMEGALOVIRUS MYOCARDITIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ENDOMETRITIS BACTERIAL
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    DISSEMINATED CYTOMEGALOVIRAL INFECTION
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    UROSEPSIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    ORAL CANDIDIASIS
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    MENINGITIS CRYPTOCOCCAL
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    KLEBSIELLA BACTERAEMIA
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    HERPES ZOSTER
         subjects affected / exposed
    3 / 61 (4.92%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 61 (1.64%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    VARICELLA
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    TUBERCULOSIS
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    SEPSIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    APPENDICITIS
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    PNEUMONIA ASPIRATION
         subjects affected / exposed
    0 / 61 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    HYPONATRAEMIA
         subjects affected / exposed
    1 / 61 (1.64%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 PLACEBO + MMF OBINUTUZUMAB 1000MG + MMF
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    39 / 61 (63.93%)
    51 / 64 (79.69%)
    Injury, poisoning and procedural complications
    INFUSION RELATED REACTION
         subjects affected / exposed
    6 / 61 (9.84%)
    7 / 64 (10.94%)
         occurrences all number
    7
    7
    Vascular disorders
    HYPERTENSION
         subjects affected / exposed
    2 / 61 (3.28%)
    6 / 64 (9.38%)
         occurrences all number
    2
    6
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    3 / 61 (4.92%)
    5 / 64 (7.81%)
         occurrences all number
    3
    7
    General disorders and administration site conditions
    CHEST PAIN
         subjects affected / exposed
    4 / 61 (6.56%)
    0 / 64 (0.00%)
         occurrences all number
    4
    0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    4 / 61 (6.56%)
    5 / 64 (7.81%)
         occurrences all number
    6
    5
    Gastrointestinal disorders
    NAUSEA
         subjects affected / exposed
    3 / 61 (4.92%)
    6 / 64 (9.38%)
         occurrences all number
    3
    7
    DIARRHOEA
         subjects affected / exposed
    5 / 61 (8.20%)
    3 / 64 (4.69%)
         occurrences all number
    5
    3
    ABDOMINAL PAIN
         subjects affected / exposed
    3 / 61 (4.92%)
    5 / 64 (7.81%)
         occurrences all number
    3
    7
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    4 / 61 (6.56%)
    0 / 64 (0.00%)
         occurrences all number
    4
    0
    INSOMNIA
         subjects affected / exposed
    4 / 61 (6.56%)
    3 / 64 (4.69%)
         occurrences all number
    4
    3
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    4 / 61 (6.56%)
    5 / 64 (7.81%)
         occurrences all number
    5
    6
    Infections and infestations
    CONJUNCTIVITIS
         subjects affected / exposed
    2 / 61 (3.28%)
    4 / 64 (6.25%)
         occurrences all number
    2
    6
    BRONCHITIS
         subjects affected / exposed
    5 / 61 (8.20%)
    13 / 64 (20.31%)
         occurrences all number
    8
    15
    URINARY TRACT INFECTION
         subjects affected / exposed
    12 / 61 (19.67%)
    14 / 64 (21.88%)
         occurrences all number
    20
    19
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    5 / 61 (8.20%)
    6 / 64 (9.38%)
         occurrences all number
    6
    8
    PHARYNGITIS
         subjects affected / exposed
    4 / 61 (6.56%)
    5 / 64 (7.81%)
         occurrences all number
    4
    8
    NASOPHARYNGITIS
         subjects affected / exposed
    6 / 61 (9.84%)
    5 / 64 (7.81%)
         occurrences all number
    8
    5
    HERPES ZOSTER
         subjects affected / exposed
    6 / 61 (9.84%)
    5 / 64 (7.81%)
         occurrences all number
    7
    6
    GASTROENTERITIS
         subjects affected / exposed
    6 / 61 (9.84%)
    3 / 64 (4.69%)
         occurrences all number
    9
    4
    INFLUENZA
         subjects affected / exposed
    2 / 61 (3.28%)
    4 / 64 (6.25%)
         occurrences all number
    3
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Jul 2015
    Additional text has been provided on ACE inhibitors and angiotensin-receptor blockers with regards to their known teratogenic effects.
    02 Feb 2016
    The assessment of damage throught the Glucocorticoid Toxicity Change Index (GTCI) was added as an exploratory objective. Clarifications were made that all B cells and not just CD19+ B cells will be evaluated in renal biopsies. Clarifications were made that eligible renal biopsies can be taken during screening as well as within 6 months prior to screening. The requirement for active urinary sediment to qualify patients for the study was removed. Exclusion criteria was updated. The dosing regimen for the study treatments and the follow up period were updated. Secondary objectives were updated. Procedures and process for various data collections and the time period of collection were updated.
    18 Apr 2023
    This protocol was amended primarily to update the details for the end of study. Personal identifiable information for the Medical Monitors was removed from this version. AE reporting for hospitalizations and the Sponsor's record retention was clarified. It was also clarified that summaries of clinical study results may be available in health authority databases for public access. A description of measures to protect personal data was included. Updates to the reporting term of "sudden death" and the handling and review of protocol deviations were also included.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/34615636
    http://www.ncbi.nlm.nih.gov/pubmed/37947366
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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