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    Clinical Trial Results:
    A Phase II, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of GDC-0853 in Patients with Moderate to Severe Active Systemic Lupus

    Summary
    EudraCT number
    		 2016-001039-11
    Trial protocol
    		 GB   PT   ES   BG   DE  
    Global end of trial date
    16 Jul 2019

    Results information
    Results version number
    		 v2(current)
    This version publication date
    23 Jul 2020
    First version publication date
    11 Jun 2020
    Other versions
    		 v1
    Version creation reason

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GA30044
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02908100
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH4070
    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
    16 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Jul 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the safety and efficacy of GDC-0853.
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    		 All Subjects were on immunosuppressants, antimalarials and/or corticosteroids.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 Jan 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 2 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Argentina: 23
    Country: Number of subjects enrolled
    Brazil: 63
    Country: Number of subjects enrolled
    Bulgaria: 14
    Country: Number of subjects enrolled
    Chile: 37
    Country: Number of subjects enrolled
    Colombia: 43
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Germany: 6
    Country: Number of subjects enrolled
    Korea, Republic of: 2
    Country: Number of subjects enrolled
    Mexico: 14
    Country: Number of subjects enrolled
    China: 6
    Country: Number of subjects enrolled
    United States: 42
    Worldwide total number of subjects
    260
    EEA total number of subjects
    30
    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)
    251
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 69 centers in 12 countries.

    Pre-assignment
    Screening details
    		 An overall total of 616 subjects were screened into the study, of which 356 subjects were screen failures. 260 subjects (Intent-To-Treat/ITT population) were randomized into the study, of which 1 subject did not receive any study treatment meaning that the Safety population consisted of 259 subjects.

    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
    		 Subjects received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matching GDC-0853 was administered.

    Arm title
    		 GDC-0853 (150mg) QD
    Arm description
    		 Subjects received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GDC-0853
    Investigational medicinal product code
    Other name
    Fenebrutinib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GDC-0853 was administered orally once daily (QD) at a dose of 150mg.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matching GDC-0853 was administered.

    Arm title
    		 GDC-0853 (200mg) BID
    Arm description
    		 Subjects received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GDC-0853
    Investigational medicinal product code
    Other name
    Fenebrutinib
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    GDC-0853 was administered orally twice daily (BID) at a dose of 200mg.

    Number of subjects in period 1
    		Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Started
    86
    87
    87
    Completed
    63
    66
    66
    Not completed
    23
    21
    21
         Adverse event, serious fatal
    2
    -
    -
         Non-Compliance With Contraceptive Method
    1
    -
    -
         Consent withdrawn by subject
    8
    7
    5
         Physician decision
    -
    1
    -
         Adverse event, non-fatal
    7
    6
    9
         Non-Compliance With Study Drug
    1
    1
    2
         Pregnancy
    1
    2
    -
         Randomised in Error
    1
    -
    -
         Lost to follow-up
    -
    1
    2
         Lack of efficacy
    2
    3
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Reporting group title
    GDC-0853 (150mg) QD
    Reporting group description
    		 Subjects received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Reporting group title
    GDC-0853 (200mg) BID
    Reporting group description
    		 Subjects received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Reporting group values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID Total
    Number of subjects
    		 86 87 87 260
    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)
    		 83 83 85 251
        From 65-84 years
    		 3 4 2 9
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 40.2 ± 11.5 43.3 ± 12.4 40.4 ± 10.6 -
    Sex: Female, Male
    Units:
        Female
    		 85 82 84 251
        Male
    		 1 5 3 9
    Race/Ethnicity, Customized
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 54 61 61 176
        Not Hispanic or Latino
    		 32 25 26 83
        Not Stated
    		 0 1 0 1
    Race/Ethnicity, Customized
    Race
    Units: Subjects
        American Indian or Alaska native
    		 11 8 17 36
        Asian
    		 7 1 2 10
        Black or African American
    		 11 15 13 39
        Multiple
    		 1 1 3 5
        White
    		 56 62 52 170

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Reporting group title
    GDC-0853 (150mg) QD
    Reporting group description
    		 Subjects received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Reporting group title
    GDC-0853 (200mg) BID
    Reporting group description
    		 Subjects received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Subject analysis set title
    Placebo (Safety-Evaluable Population)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. The Safety-evaluable population was defined as all subjects who received at least one dose of study medication. One subject in the Placebo arm was inadvertently dosed with GDC-0853 for a period of 27 days and was classified as part of the GDC-0853 (200mg) BID arm.

    Subject analysis set title
    GDC-0853 (150mg) QD (Safety-Evaluable Population)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. The Safety-evaluable population was defined as all subjects who received at least one dose of study medication. One subject in the Placebo arm was inadvertently dosed with GDC-0853 for a period of 27 days and was classified as part of the GDC-0853 (200mg) BID arm.

    Subject analysis set title
    GDC-0853 (200mg) BID (Safety-Evaluable Population)
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Subjects received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. The Safety-evaluable population was defined as all subjects who received at least one dose of study medication. One subject in the Placebo arm was inadvertently dosed with GDC-0853 for a period of 27 days and was classified as part of the GDC-0853 (200mg) BID arm.

    Subject analysis set title
    Placebo (BICLA-Evaluable Population)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. The BICLA-evaluable population was defined as all ITT subjects who had at least one body system with moderate or severe disease activity at baseline as determined by BILAG-2004, i.e., at least one BILAG domain was scored as A or B at baseline.

    Subject analysis set title
    GDC-0853 (150mg) QD (BICLA-Evaluable Population)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. The BICLA-evaluable population was defined as all ITT subjects who had at least one body system with moderate or severe disease activity at baseline as determined by BILAG-2004, i.e., at least one BILAG domain was scored as A or B at baseline.

    Subject analysis set title
    GDC-0853 (200mg) BID (BICLA-Evaluable Population)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subjects received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy. The BICLA-evaluable population was defined as all ITT subjects who had at least one body system with moderate or severe disease activity at baseline as determined by BILAG-2004, i.e., at least one BILAG domain was scored as A or B at baseline.

    Primary: Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48

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    End point title
    		 Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48
    End point description
    The Systemic Lupus Erythematosus Responder Index (SRI)-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    86
    87
    87
    Units: Percentage of Subjects
        number (not applicable)
    44.2
    50.6
    51.7
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.373
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.5
         upper limit
    		 21.2
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.339
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.3
         upper limit
    		 22.4

    Secondary: SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams per Day (mg/day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48

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    End point title
    		 SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams per Day (mg/day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48
    End point description
    The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. OCS tapering requires a sustained reduction of OCS from Week 36 through Week 48 [less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1].
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    86
    87
    87
    Units: Percentage of Subjects
        number (not applicable)
    41.9
    50.6
    44.8
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.223
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    8.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 23.5
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.737
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.8
         upper limit
    		 17.7

    Secondary: SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/day and </= Day 1 Dose During Week 12 Through Week 24

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    End point title
    		 SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/day and </= Day 1 Dose During Week 12 Through Week 24
    End point description
    The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. OCS tapering requires a sustained reduction of OCS from Week 12 through Week 24 [less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1].
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    86
    87
    87
    Units: Percentage of Subjects
        number (not applicable)
    43.0
    47.1
    47.1
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.614
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.7
         upper limit
    		 18.9
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.607
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    4.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.7
         upper limit
    		 18.9

    Secondary: SRI-4 Response at Week 24

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    End point title
    		 SRI-4 Response at Week 24
    End point description
    The Systemic Lupus Erythematosus Responder Index (SRI)-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    86
    87
    87
    Units: Percentage of Subjects
        number (not applicable)
    46.5
    52.9
    52.9
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.41
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.5
         upper limit
    		 21.2
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.418
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    6.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.5
         upper limit
    		 21.2

    Secondary: SRI-4 response at Week 48 in patients with high vs. low plasmablast signature levels

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    End point title
    		 SRI-4 response at Week 48 in patients with high vs. low plasmablast signature levels
    End point description
    The SRI-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. The Plasmablast Signature (PB) is a Bruton’s Tyrosine Kinase (BTK)-dependent blood RNA signature comprised of three genes (IgJ, MZB1 and TXNDC5). PBS LvL = Plasmablast Signature Level. Pla (n=X); 150 (n=X) and 200 (n=X) = Number of Subjects analysed in each arm at each plasmablast level. Q=Quartile.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    24 [1]
    24 [2]
    25 [3]
    Units: Percentage of Subjects
    number (not applicable)
        PBS LvL Q1 Pla (n=24); 150 (n=21); 200 (n=20)
    37.5
    52.4
    45.0
        PBS LvL Q2 Pla (n=22); 150 (n=24); 200 (n=19)
    54.5
    54.2
    63.2
        PBS LvL Q3 Pla (n=19); 150 (n=21); 200 (n=25)
    36.8
    52.4
    52.0
        PBS LvL Q4 Pla (n=20); 150 (n=21); 200 (n=23)
    50.0
    42.9
    47.8
    Notes
    [1] - Data presented is only for subjects that were included in the actual analysis.
    [2] - Data presented is only for subjects that were included in the actual analysis.
    [3] - Data presented is only for subjects that were included in the actual analysis.
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q1
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.378
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    14.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14
         upper limit
    		 43.7
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q1
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.732
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    7.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.7
         upper limit
    		 36.7
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q2
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.2
         upper limit
    		 28.4
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q2
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.234
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    8.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.4
         upper limit
    		 38.7
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q3
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.364
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    15.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.9
         upper limit
    		 46
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q3
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.134
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    15.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.1
         upper limit
    		 44.4
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q4
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.83
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -7.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -37.6
         upper limit
    		 23.3
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q4
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.963
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -2.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.1
         upper limit
    		 27.8

    Secondary: SRI-4 response with a sustained reduction of OCS dose to ≤ 10 mg/day and ≤ Day 1 dose during Week 36 through 48 in patients with high vs. low plasmablast signature levels

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    End point title
    		 SRI-4 response with a sustained reduction of OCS dose to ≤ 10 mg/day and ≤ Day 1 dose during Week 36 through 48 in patients with high vs. low plasmablast signature levels
    End point description
    The SRI-4 measures reduction in SLE disease activity and is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity. OCS tapering requires a sustained reduction of OCS from Week 36 through Week 48 [less than 10 milligram per day (mg/day) and less or equal to the dose received on Day 1]. Plasmablast Signature is a BTK-dependent blood RNA signature comprised of three genes (IgJ, MZB1 and TXNDC5). PBS LvL = Plasmablast Signature Level. Plac (n=X); 150 (n=X) and 200 (n=X) = Number of Subjects analysed in each arm at each Plasmablast Signature Level. Q=Quartile.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    24 [4]
    24 [5]
    25 [6]
    Units: Percentage of Subjects
    number (not applicable)
        PBS LvL Q1 Pla (n=24); 150 (n=21); 200 (n=20)
    33.3
    52.4
    40.0
        PBS LvL Q2 Pla (n=22); 150 (n=24); 200 (n=19)
    54.5
    54.2
    57.9
        PBS LvL Q3 Pla (n=19); 150 (n=21); 200 (n=25)
    36.8
    52.4
    44.0
        PBS LvL Q4 Pla (n=20); 150 (n=21); 200 (n=23)
    45.0
    42.9
    39.1
    Notes
    [4] - Data presented is only for subjects that were included in the actual analysis.
    [5] - Data presented is only for subjects that were included in the actual analysis.
    [6] - Data presented is only for subjects that were included in the actual analysis.
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q1
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.189
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    19
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.4
         upper limit
    		 47.5
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q1
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.909
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    6.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.9
         upper limit
    		 35.2
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q2
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.5
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29.2
         upper limit
    		 28.4
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q2
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.234
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    3.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.1
         upper limit
    		 33.8
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q3
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.364
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    15.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.9
         upper limit
    		 46
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q3
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.31
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    7.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -22
         upper limit
    		 36.3
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q4
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.922
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -32.5
         upper limit
    		 28.2
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Plasmablast Signature Level Q4
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.701
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -5.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.4
         upper limit
    		 23.7

    Secondary: SRI-6 Response at Week 24 and 48

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    End point title
    		 SRI-6 Response at Week 24 and 48
    End point description
    The Systemic Lupus Erythematosus Responder Index (SRI)-6 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥6 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [10 mm] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
    End point type
    Secondary
    End point timeframe
    Week 24, 48
    End point values
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    86
    87
    87
    Units: Percentage of Subjects
    number (not applicable)
        Week 24
    31.4
    34.5
    33.3
        Week 48
    27.9
    39.1
    35.6
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Week 24
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.692
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.9
         upper limit
    		 17.1
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Week 24
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.871
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12
         upper limit
    		 15.9
    Statistical analysis title
    		 GDC-0853 (150mg) versus Placebo
    Statistical analysis description
    Week 48
    Comparison groups
    Placebo v GDC-0853 (150mg) QD
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.105
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    11.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 25.1
    Statistical analysis title
    		 GDC-0853 (200mg) versus Placebo
    Statistical analysis description
    Week 48
    Comparison groups
    Placebo v GDC-0853 (200mg) BID
    Number of subjects included in analysis
    173
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.286
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    7.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 21.6

    Secondary: BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48

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    End point title
    		 BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48
    End point description
    The BICLA is a composite index that is defined as follows: [1] At least one gradation of improvement in baseline BILAG scores in all body systems with moderate or severe disease activity at entry (e.g., all A (severe disease) scores falling to B (moderate), C (mild), or D (no activity) and all B scores falling to C or D; [2] No new BILAG A or more than one new BILAG B scores; [3] No worsening of total SLEDAI-2K score from baseline; [4] No significant deterioration (=<10%) in physician’s global assessment and [5] No treatment failure (initiation of non-protocol treatment).
    End point type
    Secondary
    End point timeframe
    Week 24, 48
    End point values
    		 Placebo (BICLA-Evaluable Population) GDC-0853 (150mg) QD (BICLA-Evaluable Population) GDC-0853 (200mg) BID (BICLA-Evaluable Population)
    Number of subjects analysed
    80
    85
    83
    Units: Percentage of Subjects
    number (not applicable)
        Week 24
    47.5
    45.9
    44.6
        Week 48
    41.2
    52.9
    42.2
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Week 24
    Comparison groups
    Placebo (BICLA-Evaluable Population) v GDC-0853 (150mg) QD (BICLA-Evaluable Population)
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.936
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.8
         upper limit
    		 13.6
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Week 24
    Comparison groups
    Placebo (BICLA-Evaluable Population) v GDC-0853 (200mg) BID (BICLA-Evaluable Population)
    Number of subjects included in analysis
    163
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.683
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    -2.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -18.2
         upper limit
    		 12.4
    Statistical analysis title
    		 GDC-0853 (150mg) QD versus Placebo
    Statistical analysis description
    Week 48
    Comparison groups
    Placebo (BICLA-Evaluable Population) v GDC-0853 (150mg) QD (BICLA-Evaluable Population)
    Number of subjects included in analysis
    165
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.086
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    11.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.4
         upper limit
    		 26.8
    Statistical analysis title
    		 GDC-0853 (200mg) BID versus Placebo
    Statistical analysis description
    Week 48
    Comparison groups
    Placebo (BICLA-Evaluable Population) v GDC-0853 (200mg) BID (BICLA-Evaluable Population)
    Number of subjects included in analysis
    163
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.879
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Absolute Difference
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.2
         upper limit
    		 16.1

    Secondary: Percentage of Subjects With Adverse Events (AEs)

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    End point title
    		 Percentage of Subjects With Adverse Events (AEs)
    End point description
    An Adverse Event is any untoward medical occurrence in a subject 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.
    End point type
    Secondary
    End point timeframe
    Baseline up to 8 weeks after the last dose of study drug (up to Week 56).
    End point values
    		 Placebo (Safety-Evaluable Population) GDC-0853 (150mg) QD (Safety-Evaluable Population) GDC-0853 (200mg) BID (Safety-Evaluable Population)
    Number of subjects analysed
    84
    87
    88
    Units: Percentage of Subjects
        number (not applicable)
    76.2
    88.5
    78.4
    No statistical analyses for this end point

    Secondary: Plasma Concentrations of Fenebrutinib at specified timepoints

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    End point title
    		 Plasma Concentrations of Fenebrutinib at specified timepoints [7]
    End point description
    The PK analyses includes tabulation of plasma concentration data and summarisation of plasma concentrations by visits with subjects grouped according to treatment received. Descriptive summary statistics for the Arithmetic Mean and Standard Deviation are presented below. The PK-evaluable population was defined as all subjects who received at least one dose of fenebrutinib (GDC-0853) and had at least 1 evaluable post-dose PK sample. 999 = Not Estimable. 150 (n=X); 200 (n=X) = Number of Subjects analysed in each arm at each timepoint.
    End point type
    Secondary
    End point timeframe
    Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose)
    Notes
    [7] - 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: PK Analysis was only carried out on the treatment groups and not on the Placebo group.
    End point values
    		 GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Number of subjects analysed
    87 [8]
    86 [9]
    Units: ng/mL
    arithmetic mean (standard deviation)
        Wk 0 (Pre-dose) 150 (n=87) 200 (n=86)
    999 ± 999
    999 ± 999
        Wk 24 (Pre-dose) 150 (n=67) 200 (n=68)
    41.9 ± 62.4
    180 ± 121
        Wk 24 (2hr Post-dose) 150 (n=66) 200 (n=67)
    331 ± 226
    612 ± 353
        Wk 24 (4-6hr Post-dose) 150 (n=65) 200 (n=66)
    215 ± 131
    414 ± 187
        Wk 24 (8-10hr Post-dose) 150 (n=11) 200 (n=7)
    120 ± 111
    233 ± 145
        Week 48 (Pre-dose) 150 (n=64) 200 (n=64)
    25.5 ± 28.1
    137 ± 133
    Notes
    [8] - Data presented is only for subjects that were included in the actual analysis.
    [9] - Data presented is only for subjects that were included in the actual analysis.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline up to 8 weeks after the last dose of study drug (up to Week 56).
    Adverse event reporting additional description
    The Safety Population was defined as all subjects who received at least one dose of study medication. AEs that were entered into the database at the time of the database lock were included in the AE analysis.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received matching placebo to GDC-0853 orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Reporting group title
    GDC-0853 (150mg) QD
    Reporting group description
    		 Subjects received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Reporting group title
    GDC-0853 (200mg) BID
    Reporting group description
    		 Subjects received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.

    Serious adverse events
    		 Placebo GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 84 (10.71%)
    4 / 87 (4.60%)
    12 / 88 (13.64%)
         number of deaths (all causes)
    2
    1
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CERVIX CARCINOMA STAGE 0
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SALIVARY GLAND NEOPLASM
         subjects affected / exposed
    0 / 84 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    Surgical and medical procedures
    ABORTION INDUCED
         subjects affected / exposed
    0 / 84 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (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
    Pregnancy, puerperium and perinatal conditions
    ABORTION SPONTANEOUS
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    General disorders and administration site conditions
    MULTIPLE ORGAN DYSFUNCTION SYNDROME
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    PYREXIA
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    ACUTE RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    PULMONARY OEDEMA
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    RESPIRATORY FAILURE
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    Psychiatric disorders
    DEPRESSION
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    Investigations
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    Injury, poisoning and procedural complications
    ANKLE FRACTURE
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    CONGESTIVE CARDIOMYOPATHY
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    MYOCARDITIS
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    SYNCOPE
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    LEUKOCYTOSIS
         subjects affected / exposed
    0 / 84 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (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
    THROMBOCYTOPENIA
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    SKIN ULCER
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    Renal and urinary disorders
    RENAL COLIC
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         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 IMPAIRMENT
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    CHEST WALL HAEMATOMA
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    MUSCULAR WEAKNESS
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PAIN IN EXTREMITY
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SYSTEMIC LUPUS ERYTHEMATOSUS
         subjects affected / exposed
    2 / 84 (2.38%)
    1 / 87 (1.15%)
    2 / 88 (2.27%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    EPSTEIN-BARR VIRUS INFECTION
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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 BACTERIAL
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    INFECTED SKIN ULCER
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    OSTEOMYELITIS CHRONIC
         subjects affected / exposed
    0 / 84 (0.00%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    PULMONARY TUBERCULOSIS
         subjects affected / exposed
    0 / 84 (0.00%)
    1 / 87 (1.15%)
    0 / 88 (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
    PYELONEPHRITIS
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    SEPTIC SHOCK
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    0 / 88 (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
    URINARY TRACT INFECTION
         subjects affected / exposed
    1 / 84 (1.19%)
    0 / 87 (0.00%)
    1 / 88 (1.14%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
         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 GDC-0853 (150mg) QD GDC-0853 (200mg) BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    42 / 84 (50.00%)
    54 / 87 (62.07%)
    51 / 88 (57.95%)
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    9 / 84 (10.71%)
    3 / 87 (3.45%)
    3 / 88 (3.41%)
         occurrences all number
    10
    4
    3
    Blood and lymphatic system disorders
    LYMPHOPENIA
         subjects affected / exposed
    6 / 84 (7.14%)
    2 / 87 (2.30%)
    10 / 88 (11.36%)
         occurrences all number
    6
    2
    12
    NEUTROPENIA
         subjects affected / exposed
    4 / 84 (4.76%)
    5 / 87 (5.75%)
    6 / 88 (6.82%)
         occurrences all number
    5
    5
    6
    Gastrointestinal disorders
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    1 / 84 (1.19%)
    2 / 87 (2.30%)
    5 / 88 (5.68%)
         occurrences all number
    1
    2
    7
    DIARRHOEA
         subjects affected / exposed
    6 / 84 (7.14%)
    5 / 87 (5.75%)
    5 / 88 (5.68%)
         occurrences all number
    6
    8
    6
    NAUSEA
         subjects affected / exposed
    7 / 84 (8.33%)
    4 / 87 (4.60%)
    7 / 88 (7.95%)
         occurrences all number
    7
    4
    7
    Skin and subcutaneous tissue disorders
    RASH
         subjects affected / exposed
    0 / 84 (0.00%)
    3 / 87 (3.45%)
    6 / 88 (6.82%)
         occurrences all number
    0
    3
    8
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    2 / 84 (2.38%)
    1 / 87 (1.15%)
    5 / 88 (5.68%)
         occurrences all number
    4
    1
    6
    BACK PAIN
         subjects affected / exposed
    2 / 84 (2.38%)
    8 / 87 (9.20%)
    4 / 88 (4.55%)
         occurrences all number
    3
    9
    4
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    6 / 84 (7.14%)
    6 / 87 (6.90%)
    7 / 88 (7.95%)
         occurrences all number
    7
    6
    9
    GASTROENTERITIS
         subjects affected / exposed
    5 / 84 (5.95%)
    2 / 87 (2.30%)
    2 / 88 (2.27%)
         occurrences all number
    7
    2
    2
    INFLUENZA
         subjects affected / exposed
    5 / 84 (5.95%)
    5 / 87 (5.75%)
    5 / 88 (5.68%)
         occurrences all number
    8
    5
    5
    NASOPHARYNGITIS
         subjects affected / exposed
    5 / 84 (5.95%)
    8 / 87 (9.20%)
    6 / 88 (6.82%)
         occurrences all number
    6
    12
    6
    SINUSITIS
         subjects affected / exposed
    3 / 84 (3.57%)
    2 / 87 (2.30%)
    5 / 88 (5.68%)
         occurrences all number
    3
    2
    5
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    5 / 84 (5.95%)
    9 / 87 (10.34%)
    3 / 88 (3.41%)
         occurrences all number
    7
    10
    3
    URINARY TRACT INFECTION
         subjects affected / exposed
    9 / 84 (10.71%)
    17 / 87 (19.54%)
    11 / 88 (12.50%)
         occurrences all number
    11
    21
    15

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 May 2017
    Following updates were made: [1] Better characterisation of Primary SRI-4 endpoint, addition of an endpoint to better capture changes in skin and joint domains and endpoint has been added to assess improvement in Patient’s Global Assessment at Weeks 24 and 48; [2] Extension of Screening period from 28 to 35 days; [3] Clarification of language on angiotensin converting enzyme inhibitors and angiotensin receptor blockers, steroid burst treatment and the SELENA-SLEDAI disease activity index being updated to SLEDAI-2K; [4] Update to timing of Interim analysis; [5] Updates to Eligibility criteria; [6] Clarification of language relating to dosing schedules, site responsibilities, injections of corticosteroids and dosage of antimalarials; [7] Update to Prohibited Therapies section; [8] Clarification of language around fasting requirements, requirements for chest radiography, SLE disease activity instruments, endpoints, training requirements and clinical manifestations, laboratory tests and reporting of terms and events; [9] Updates made to the Statistical Considerations and Analysis Plan and Schedule of Assessments and [10] Further updates made to the Appendices and Indexes.
    09 Feb 2018
    Following updates were made: [1] Modification to the Study Design Figure; [2] Updates and re-categorisation to SRI secondary efficacy endpoints; [3] Updates to PK objectives and endpoints; [4] Clarification to language for nonclinical efficacy data for the BTK inhibitor GDC-0834; [5] Update to minimum SLEDAI-2K score requirement for subjects to enrol in the study; [6] Updates to Inclusion/Exclusion criteria; [7] Updates to language regarding study drug administration, dosage and steroid burst treatment and tapering; [8] Updates to the Prohibited Therapies section and [9] Other updates including to the Hepatotoxicity language, analysis for Primary endpoint and PK, measurements to be carried out at Week 48 and PD Biomarkers.

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

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

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