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    Clinical Trial Results:
    A Two-Cohort Randomized Phase II, Double-Blind, Parallel Group Study in Patients with Active Rheumatoid Arthritis Evaluating the Efficacy and Safety of GDC-0853 Compared with Placebo and Adalimumab in Patients with an Inadequate Response to Previous Methotrexate Therapy (Cohort 1) and Compared with Placebo in Patients with an Inadequate Response or Intolerance to Previous TNF Therapy (Cohort 2).

    Summary
    EudraCT number
    2016-000335-40
    Trial protocol
    BG  
    Global end of trial date
    02 Jul 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    18 Jul 2019
    First version publication date
    18 Jul 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GA29350
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02833350
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Hoffmann-La Roche AG, Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    Medical Communications, Hoffmann-La Roche AG, 41 616878333, globa.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 Jul 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    02 Jul 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Jul 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy and safety of GDC-0853 in patients with moderate to severe active RA and an inadequate response to previous MTX therapy (Cohort 1) or MTX and TNF therapy who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form.
    Background therapy
    Patients with moderate to severe active (RA) and an inadequate response to previous methotrexate (MTX) therapy (Cohort 1) or inadequate response or intolerance to one or two TNF inhibitors and MTX therapy, and who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).
    Evidence for comparator
    -
    Actual start date of recruitment
    09 Sep 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Ukraine: 154
    Country: Number of subjects enrolled
    United States: 27
    Country: Number of subjects enrolled
    Argentina: 63
    Country: Number of subjects enrolled
    Brazil: 56
    Country: Number of subjects enrolled
    Bulgaria: 40
    Country: Number of subjects enrolled
    Colombia: 31
    Country: Number of subjects enrolled
    Mexico: 46
    Country: Number of subjects enrolled
    Poland: 33
    Country: Number of subjects enrolled
    Russian Federation: 91
    Country: Number of subjects enrolled
    Serbia: 37
    Worldwide total number of subjects
    578
    EEA total number of subjects
    73
    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)
    506
    From 65 to 84 years
    72
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    578 participants were enrolled in the study and 578 were dosed. One (1) subject in Cohort 2 in the Placebo arm was incorrectly dosed with the High Dose. The ITT data set included participants according to their randomization while SAF data set included participants according to the treatment administered.

    Pre-assignment
    Screening details
    Participants with moderate to severe active RA and an inadequate response to previous MTX therapy (Cohort 1) or inadequate response or intolerance to one or two TNF inhibitors and MTX therapy, and who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).

    Period 1
    Period 1 title
    Randomized
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    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
    50 mg

    Investigational medicinal product name
    Adalimumab Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    Arm title
    Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX was the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab Placeb
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    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
    150 MG

    Arm title
    Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX was the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab Placeb
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    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
    200 mg

    Arm title
    Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Placebo

    Investigational medicinal product name
    GDC-0853 Placebo
    Investigational medicinal product code
    Other name
    Fenebrutinib Placebo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    N/A

    Investigational medicinal product name
    Adalimumab Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    Arm title
    Cohort 1: GDC-0853 Placebo + Adalimumab
    Arm description
    Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Active comparator

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg

    Investigational medicinal product name
    GDC-0853 Placebo
    Investigational medicinal product code
    Other name
    GDC-0853 Placebo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    N/A

    Arm title
    Cohort 2: GDC-0853 High Dose
    Arm description
    Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    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
    200 mg

    Arm title
    Cohort 2: GDC-0853 Placebo
    Arm description
    Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Placebo

    Investigational medicinal product name
    GDC-0853 Placebo
    Investigational medicinal product code
    Other name
    Fenebrutinib Placebo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    N/A

    Number of subjects in period 1
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Started
    40
    109
    110
    110
    111
    48
    50
    Completed
    40
    109
    110
    110
    111
    48
    50
    Period 2
    Period 2 title
    Treated
    Is this the baseline period?
    Yes [1]
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    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
    50 mg

    Arm title
    Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab Placeb
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    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
    150 MG

    Arm title
    Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Experimental

    Investigational medicinal product name
    Adalimumab Placeb
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    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
    200 mg

    Arm title
    Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Arm description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Placebo

    Investigational medicinal product name
    Adalimumab Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    N/A

    Investigational medicinal product name
    GDC-0853 Placebo
    Investigational medicinal product code
    Other name
    Fenebrutinib Placebo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    N/A

    Arm title
    Cohort 1: GDC-0853 Placebo + Adalimumab
    Arm description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Active comparator

    Investigational medicinal product name
    GDC-0853 Placebo
    Investigational medicinal product code
    Other name
    GDC-0853 Placebo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    N/A

    Investigational medicinal product name
    Adalimumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    40 mg

    Arm title
    Cohort 2: GDC-0853 High Dose
    Arm description
    Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    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
    200 mg

    Arm title
    Cohort 2: GDC-0853 Placebo
    Arm description
    Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Arm type
    Placebo

    Investigational medicinal product name
    GDC-0853 Placebo
    Investigational medicinal product code
    Other name
    Fenebrutinib Placebo
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    N/A

    Notes
    [1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
    Justification: This endpoint was specific for Cohort 1 only.
    Number of subjects in period 2
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Started
    40
    109
    110
    110
    111
    49
    49
    Completed
    37
    100
    102
    102
    108
    48
    44
    Not completed
    3
    9
    8
    8
    3
    1
    5
         Lack of efficacy
    -
    2
    1
    4
    -
    1
    1
         Adverse event, serious fatal
    -
    -
    1
    -
    -
    -
    -
         Adverse event, non-fatal
    -
    3
    4
    4
    1
    -
    1
         Consent withdrawn by subject
    3
    3
    2
    -
    2
    -
    2
         Lost to follow-up
    -
    1
    -
    -
    -
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab
    Reporting group description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 High Dose
    Reporting group description
    Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 Placebo
    Reporting group description
    Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo Total
    Number of subjects
    40 109 110 110 111 49 49 578
    Age Categorical
    Units: Subjects
        <=18 years
    0 0 0 0 0 0 0 0
        Between 18 and 65 years
    35 95 99 98 98 41 40 506
        >=65 years
    5 14 11 12 13 8 9 72
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    52.3 ± 12.0 50.4 ± 11.0 49.9 ± 12.4 50.2 ± 11.6 49.9 ± 12.4 51.3 ± 13.2 54.6 ± 11.5 -
    Sex: Female, Male
    Units: Subjects
        Female
    35 92 85 90 87 37 37 463
        Male
    5 17 25 20 24 12 12 115
    Race/Ethnicity, Customized
    Race
    Units: Subjects
        American Indian or Alaska native
    0 8 12 11 9 6 5 51
        Asian
    1 0 0 0 0 0 0 1
        Black of African American
    0 1 2 3 1 1 2 10
        White
    36 96 96 95 99 42 42 506
        Multiple
    3 2 0 1 1 0 0 7
        Unknown
    0 2 0 0 1 0 0 3
    Race/Ethnicity, Customized
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    8 38 40 38 39 17 15 195
        Not Hispanic or Latino
    31 68 69 72 70 32 33 375
        Not Stated
    0 1 1 0 0 0 1 3
        Unknown
    1 2 0 0 2 0 0 5

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 received GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 received GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX was the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 received GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX was the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab
    Reporting group description
    Participants of Cohort 1 received placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 High Dose
    Reporting group description
    Participants of Cohort 2 received GDC-0853 high dose, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 Placebo
    Reporting group description
    Participants of Cohort 2 received placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants remained on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week were allowed only if there was clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
    Reporting group title
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab
    Reporting group description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 High Dose
    Reporting group description
    Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 Placebo
    Reporting group description
    Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Primary: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1)

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    End point title
    Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1)
    End point description
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
    End point type
    Primary
    End point timeframe
    Day 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab
    Number of subjects analysed
    40
    109
    110
    110
    111
    Units: Percentage
        number (confidence interval 95%)
    17.5 (5.72 to 29.28)
    27.5 (19.14 to 35.91)
    34.5 (25.66 to 43.43)
    14.5 (7.96 to 21.13)
    36.0 (27.10 to 44.97)
    Statistical analysis title
    Week 12 Day 84
    Comparison groups
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo v Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Number of subjects included in analysis
    150
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.2503
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Weighted difference
    Point estimate
    8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -5.64
         upper limit
    21.64
    Statistical analysis title
    Week 12 Day 84
    Comparison groups
    Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo v Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Number of subjects included in analysis
    219
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.0164
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Weighted difference
    Point estimate
    12.93
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    2.37
         upper limit
    23.48
    Statistical analysis title
    Week 12 Day 84
    Comparison groups
    Cohort 1: GDC-0853 High Dose + Adalimumab Placebo v Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Number of subjects included in analysis
    220
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    = 0.0003
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Weighted difference
    Point estimate
    20
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    9.21
         upper limit
    30.79

    Primary: Percentage of Participants With Adverse Events

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    End point title
    Percentage of Participants With Adverse Events [1]
    End point description
    An Adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. Safety population included all participants according to treatment administered.
    End point type
    Primary
    End point timeframe
    Day 1 up to 8 weeks after last dose (up to Week 20)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive statistics are presented for this measure. No statistical analyses were planned.
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    49
    49
    Units: Percentage of participants
        number (not applicable)
    37.5
    42.2
    50.9
    45.5
    45.0
    22.4
    44.9
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1)

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    End point title
    Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1)
    End point description
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
    End point type
    Secondary
    End point timeframe
    Day 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab
    Number of subjects analysed
    40
    109
    110
    110
    111
    Units: Percentage
        number (confidence interval 95%)
    17.5 (5.72 to 29.28)
    27.5 (19.14 to 35.91)
    34.5 (25.66 to 43.43)
    14.5 (7.96 to 21.13)
    36.0 (27.10 to 44.97)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2)

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    End point title
    Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2)
    End point description
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
    End point type
    Secondary
    End point timeframe
    Day 84
    End point values
    Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    48
    50
    Units: Percentage
        number (confidence interval 95%)
    25.0 (12.75 to 37.25)
    12.0 (2.99 to 21.01)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response

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    End point title
    Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
    End point description
    ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage
    number (confidence interval 95%)
        Week 1 Day 7
    10.0 (.70 to 19.3)
    14.7 (8.04 to 21.32)
    13.6 (7.22 to 20.05)
    10.0 (4.39 to 15.61)
    25.2 (17.15 to 33.30)
    22.9 (11.03 to 34.81)
    2.0 (0.00 to 5.88)
        Week 2 Day 14
    12.5 (2.25 to 22.75)
    19.3 (11.86 to 26.67)
    27.3 (18.95 to 35.60)
    16.4 (9.45 to 23.28)
    48.6 (39.35 to 57.95)
    25.0 (12.75 to 37.25)
    10.0 (1.68 to 18.32)
        Week 4 Day 28
    30.0 (15.80 to 44.20)
    34.9 (25.92 to 43.81)
    41.8 (32.60 to 51.04)
    25.5 (17.31 to 33.59)
    59.5 (50.33 to 68.59)
    35.4 (21.89 to 48.95)
    24.0 (12.16 to 35.84)
        Week 8 Day 56
    50.0 (34.51 to 65.49)
    52.3 (42.92 to 61.67)
    58.2 (48.96 to 67.40)
    37.3 (28.24 to 46.31)
    71.2 (62.74 to 79.60)
    47.9 (33.78 to 62.05)
    18.0 (7.35 to 28.65)
        Week 12 Day 84
    60.0 (44.82 to 75.18)
    56.0 (46.64 to 65.28)
    59.1 (49.90 to 68.28)
    36.4 (27.37 to 45.35)
    72.1 (63.73 to 80.42)
    58.3 (44.39 to 72.28)
    24.0 (12.16 to 35.84)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response

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    End point title
    Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
    End point description
    ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage
    number (confidence interval 95%)
        Week 1 Day 7
    2.5 (0.00 to 7.34)
    2.8 (0.00 to 5.82)
    3.6 (0.14 to 7.13)
    2.7 (0.00 to 5.77)
    4.5 (0.65 to 8.36)
    6.3 (0.00 to 13.10)
    2.0 (0.00 to 5.88)
        Week 2 Day 14
    0.0 (0.00 to 0.00)
    1.8 (0.00 to 4.35)
    7.3 (2.42 to 12.13)
    2.7 (0.00 to 5.77)
    9.0 (3.68 to 14.34)
    10.4 (1.77 to 19.06)
    0.00 (0.00 to 0.00)
        Week 4 day 28
    5.0 (0.00 to 11.75)
    9.2 (3.76 to 14.59)
    10.0 (4.39 to 15.61)
    6.4 (1.80 to 10.93)
    25.2 (17.15 to 33.30)
    10.4 (1.77 to 19.06)
    6.0 (0.00 to 12.58)
        Week 8 Day 56
    15.0 (3.93 to 26.07)
    18.3 (11.08 to 25.62)
    22.7 (14.9 to 30.56)
    17.3 (10.21 to 24.34)
    32.4 (23.72 to 41.14)
    22.9 (11.03 to 34.81)
    10.0 (1.68 to 18.32)
        Week 12 Day 84
    17.5 (5.72 to 29.28)
    27.5 (19.14 to 35.91)
    34.5 (25.66 to 43.43)
    14.5 (7.96 to 21.13)
    36.0 (27.10 to 44.97)
    25.0 (12.75 to 37.25)
    12.0 (2.99 to 21.01)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response

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    End point title
    Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
    End point description
    ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage
    number (confidence interval 95%)
        Week 1 Day 7
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.71)
    0.9 (0.00 to 2.68)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 2 Day 14
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.71)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    3.6 (0.14 to 7.07)
    4.2 (0.00 to 9.82)
    0.0 (0.00 to 0.00)
        Week 4 Day 28
    0.0 (0.00 to 0.00)
    2.8 (0.00 to 5.82)
    4.5 (0.65 to 8.44)
    0.9 (0.00 to 2.68)
    6.3 (1.78 to 10.83)
    2.1 (0.00 to 6.12)
    2.0 (0.00 to 5.88)
        Week 8 Day 56
    0.0 (0.00 to 0.00)
    7.3 (2.44 to 12.24)
    9.1 (3.72 to 14.46)
    3.6 (0.14 to 7.13)
    14.4 (7.88 to 20.95)
    6.3 (0.00 to 13.10)
    4.0 (0.00 to 9.43)
        Week 12 Day 84
    5.0 (0.00 to 11.75)
    9.2 (3.76 to 14.59)
    12.7 (6.50 to 18.96)
    7.3 (2.42 to 12.13)
    18.0 (10.87 to 25.17)
    14.6 (4.60 to 24.57)
    4.0 (0.00 to 9.43)
    No statistical analyses for this end point

    Secondary: Change in Disease Activity Score from Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])

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    End point title
    Change in Disease Activity Score from Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
    End point description
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -0.34 ± 0.60
    -0.35 ± 0.66
    -0.37 ± 0.80
    -0.33 ± 0.84
    -0.92 ± 0.71
    -0.49 ± 0.84
    -0.36 ± 0.63
        Week 2 Day 14
    -0.47 ± 0.72
    -0.63 ± 0.84
    -0.70 ± 0.80
    -.54 ± 0.90
    -1.09 ± 0.81
    -0.65 ± 0.87
    -0.45 ± 0.69
        Week 4 Day 28
    -0.75 ± 0.86
    -0.90 ± 0.96
    -0.91 ± 0.97
    -0.62 ± 1.04
    -1.45 ± 0.87
    -0.77 ± 0.90
    -0.44 ± 0.84
        Week 8 Day 56
    -1.14 ± 0.90
    -1.35 ± 1.12
    -1.37 ± 1.11
    -1.08 ± 1.19
    -1.75 ± 0.98
    -1.33 ± 0.98
    -0.56 ± 0.87
        Week 12 Day 84
    -1.30 ± 0.95
    -1.72 ± 1.11
    -1.70 ± 1.02
    -1.17 ± 1.24
    -1.87 ± 1.02
    -1.62 ± 1.15
    -0.86 ± 1.03
    No statistical analyses for this end point

    Secondary: Change in Disease Activity Score from Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])

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    End point title
    Change in Disease Activity Score from Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
    End point description
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -0.43 ± 0.67
    -0.48 ± 0.73
    -0.49 ± 0.86
    -0.37 ± 0.91
    -1.10 ± 0.75
    -0.63 ± 0.91
    -0.40 ± 0.69
        Week 2 Day 14
    -0.51 ± 0.85
    -0.77 ± 0.86
    -0.84 ± 0.86
    -0.57 ± 1.00
    -1.26 ± 0.89
    -0.81 ± 0.98
    -0.54 ± 0.80
        Week 4 Day 28
    -0.88 ± 0.90
    -1.06 ± 1.02
    -1.08 ± 1.03
    -0.65 ± 1.16
    -1.61 ± 0.94
    -0.95 ± 1.04
    -0.55 ± 0.94
        Week 8 Day 56
    -1.31 ± 0.91
    -1.56 ± 1.21
    -1.57 ± 1.16
    -1.20 ± 1.30
    -1.97 ± 1.03
    -1.51 ± 1.05
    -0.67 ± 1.01
        Week 12 Day 84
    -1.53 ± 0.95
    -1.97 ± 1.20
    -1.93 ± 1.11
    -1.33 ± 1.33
    -2.06 ± 1.08
    -1.83 ± 1.22
    -1.00 ± 1.11
    No statistical analyses for this end point

    Secondary: Change in Disease Activity Score from Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])

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    End point title
    Change in Disease Activity Score from Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
    End point description
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -0.35 ± 0.57
    -0.42 ± 0.65
    -0.39 ± 0.68
    -0.34 ± 0.86
    -0.72 ± 0.72
    -0.50 ± 0.73
    -0.31 ± 0.60
        Week 2 Day 14
    -0.60 ± 0.89
    -0.69 ± 0.84
    -0.68 ± 0.74
    -0.55 ± 0.92
    -1.02 ± 0.84
    -0.64 ± 0.81
    -0.51 ± 0.73
        Week 4 Day 28
    -0.88 ± 0.89
    -0.99 ± 0.98
    -0.97 ± 0.90
    -0.75 ± 1.02
    -1.47 ± 1.02
    -0.85 ± 0.81
    -0.50 ± 0.83
        Week 8 Day 56
    -1.25 ± 0.85
    -1.44 ± 1.14
    -1.40 ± 1.06
    -1.15 ± 1.19
    -1.74 ± 0.98
    -1.35 ± 0.96
    -0.70 ± 0.98
        Week 12 Day 84
    -1.51 ± 1.01
    -1.80 ± 1.25
    -1.80 ± 0.99
    -1.30 ± 1.22
    -1.85 ± 1.06
    -1.65 ± 1.06
    -0.94 ± 10.6
    No statistical analyses for this end point

    Secondary: Change in Disease Activity Score from Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])

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    End point title
    Change in Disease Activity Score from Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
    End point description
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -0.45 ± 0.63
    -0.54 ± 0.72
    -0.52 ± 0.77
    -0.37 ± 0.95
    -0.93 ± 0.76
    -0.65 ± 0.80
    -0.36 ± 0.66
        Week 2 Day 14
    -0.63 ± 0.98
    -0.85 ± 0.85
    -0.84 ± 0.82
    -0.58 ± 1.03
    -1.22 ± 0.94
    -0.81 ± 0.92
    -0.60 ± 0.84
        Week 4 Day 28
    -1.00 ± 0.95
    -1.16 ± 1.06
    -1.15 ± 0.98
    -0.79 ± 1.16
    -1.65 ± 1.11
    -1.04 ± 0.95
    -0.61 ± 0.96
        Week 8 Day 56
    -1.43 ± 0.88
    -1.67 ± 1.25
    -1.63 ± 1.14
    -1.29 ± 1.31
    -2.00 ± 1.06
    -1.54 ± 1.04
    -0.81 ± 1.12
        Week 12 Day 84
    -1.76 ± 1.04
    -2.06 ± 1.36
    -2.05 ± 1.08
    -1.46 ± 1.32
    -2.08 ± 1.14
    -1.89 ± 1.15
    -1.08 ± 1.17
    No statistical analyses for this end point

    Secondary: Percentage of Participants with DAS low Disease Activity

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    End point title
    Percentage of Participants with DAS low Disease Activity
    End point description
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 ≤ 3.2
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage of participants
    number (confidence interval 95%)
        Week 1 Day 7
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.71)
    1.8 (0.00 to 4.31)
    0.0 (0.00 to 0.00)
    1.8 (0.00 to 4.28)
    2.1 (0.00 to 6.12)
    0.00 (0.00 to 0.00)
        Week 2 day 14
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    1.8 (0.00 to 4.31)
    0.9 (0.00 to 2.68)
    4.5 (0.65 to 8.36)
    2.1 (0.00 to 6.12)
    2.0 (0.00 to 5.88)
        Week 4 Day 28
    0.0 (0.00 to 0.00)
    1.8 (0.00 to 4.35)
    6.4 (1.80 to 10.93)
    1.8 (0.00 to 4.31)
    11.7 (5.73 to 17.69)
    2.1 (0.00 to 6.12)
    0.0 (0.00 to 0.00)
        Week 8 Day 56
    0.0 (0.00 to 0.00)
    8.3 (3.09 to 13.42)
    11.8 (5.79 to 17.85)
    3.6 (0.14 to 7.13)
    18.0 (10.87 to 25.17)
    2.1 (0.00 to 6.12)
    2.0 (0.00 to 5.88)
        Week 12 Day 84
    7.5 (0.00 to 15.66)
    19.3 (11.86 to 26.67)
    14.5 (7.86 to 21.13)
    3.6 (0.14 to 7.13)
    17.1 (10.11 to 24.12)
    14.6 (4.60 to 24.57)
    4.0 (0.00 to 9.43)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with DAS Remission

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    End point title
    Percentage of Participants with DAS Remission
    End point description
    The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage of participants
    number (confidence interval 95%)
        Week 1 Day 7
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    2.1 (0.00 to 6.12)
    0.0 (0.00 to 0.00)
        Week 2 Day 14
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.68)
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.66)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 4 Day 28
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    1.8 (0.00 to 4.31)
    0.9 (0.00 to 2.68)
    4.5 (0.65 to 8.36)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 8 Day 56
    0.0 (0.00 to 0.00)
    3.7 (0.14 to 7.20)
    4.5 (0.65 to 8.44)
    1.8 (0.00 to 4.31)
    9.0 (3.68 to 14.34)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 12 Day 84
    2.5 (0.00 to 7.34)
    7.3 (2.44 to 12.24)
    8.2 (3.06 to 13.30)
    3.6 (0.14 to 7.13)
    9.0 (3.68 to 14.34)
    4.2 (0.00 to 9.82)
    4.0 (0.00 to 9.43)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Meeting the Boolean-based Remission Criteria

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    End point title
    Percentage of Participants Meeting the Boolean-based Remission Criteria
    End point description
    Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale).
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage of participants
    number (confidence interval 95%)
        Week 1 Day 7
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.76)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 2 Day 14
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 4 Day 28
    0.0 (0.00 to 0.00)
    1.0 (0.00 to 2.81)
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.73)
    2.8 (0.00 to 5.82)
    2.1 (0.00 to 6.25)
    0.0 (0.00 to 0.00)
        Week 8 Day 56
    0.0 (0.00 to 0.00)
    2.0 (0.00 to 4.70)
    1.90 (0.00 to 4.56)
    1.0 (0.00 to 2.86)
    3.7 (0.14 to 7.20)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 12 Day 84
    0.0 (0.00 to 0.00)
    2.0 (0.00 to 4.84)
    4.1 (0.17 to 8.08)
    1.0 (0.00 to 2.89)
    6.5 (1.84 to 11.12)
    8.5 (0.53 to 16.49)
    0.0 (0.00 to 6.53)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Clinical Disease Activity Index (CDAI)

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    End point title
    Change from Baseline in Clinical Disease Activity Index (CDAI)
    End point description
    Clinical Disease Activity Index is defined as CDAI= : SJC(28) + TJC(28) + PGA + MDG where TJC and SJC are the tender and swollen joint counts from 28 joints, PGA is the patient’s global assessment of disease activity (on a 0-10 scale) and MDG is physician global assessment of disease activity (on a 0-10 scale). The cutoff value for CDAI remission is <=2.8
    End point type
    Secondary
    End point timeframe
    Baseline, Days 7, 14, 28, 56 and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -5.45 ± 7.69
    -6.70 ± 8.26
    -7.40 ± 9.97
    -4.71 ± 12.91
    -9.64 ± 8.93
    -8.61 ± 10.67
    -5.26 ± 9.79
        Week 2 Day 14
    -6.85 ± 11.10
    -10.33 ± 10.45
    -11.33 ± 10.47
    -7.44 ± 13.39
    -13.44 ± 10.52
    -9.64 ± 12.17
    -7.70 ± 10.64
        Week 4 Day 28
    -10.36 ± 10.88
    13.84 ± 12.11
    -13.78 ± 11.46
    -9.43 ± 14.77
    -17.74 ± 10.84
    -11.83 ± 11.08
    -7.49 ± 11.46
        Week 8 Day 56
    -14.76 ± 10.04
    -18.61 ± 13.48
    -18.10 ± 12.99
    -15.49 ± 15.74
    -21.36 ± 11.69
    -17.38 ± 12.39
    -7.57 ± 10.51
        Week 12 Day 84
    -16.99 ± 11.21
    -22.05 ± 12.19
    -22.10 ± 11.83
    -17.02 ± 16.24
    -22.22 ± 11.76
    -20.42 ± 13.20
    -12.23 ± 12.06
    No statistical analyses for this end point

    Secondary: Percentage of Participants Meeting the CDAI-based Remission Criteria

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    End point title
    Percentage of Participants Meeting the CDAI-based Remission Criteria
    End point description
    Clinical Disease Activity Index is defined as CDAI= : SJC(28) + TJC(28) + PGA + MDG where TJC and SJC are the tender and swollen joint counts from 28 joints, PGA is the patient’s global assessment of disease activity (on a 0-10 scale) and MDG is physician global assessment of disease activity (on a 0-10 scale). The cutoff value for CDAI remission is <=2.8.
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage of participants
    number (confidence interval 95%)
        Week 1 Day 7
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.71)
    0.9 (0.00 to 2.68)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 2 Day 14
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
    0.0 (0.0 to 0.00)
    0.0 (0.00 to 0.00)
    1.8 (0.00 to 4.28)
    0.0 (0.00 to 0.00)
    0.0 (0.00 to 0.00)
        Week 4 Day 28
    0.0 (0.00 to 0.00)
    0.9 (0.00 to 2.71)
    0.9 (0.00 to 2.68)
    0.0 (0.00 to 0.00)
    4.5 (0.65 to 8.36)
    2.1 (0.0 to 6.12)
    0.0 (0.00 to 0.00)
        Week 8 Day 56
    0.00 (0.0 to 0.00)
    2.8 (0.0 to 5.82)
    5.5 (1.21 to 9.70)
    0.0 (0.00 to 0.00)
    7.2 (2.40 to 12.02)
    4.2 (0.00 to 9.82)
    0.0 (0.00 to 0.00)
        Week 12 Day 84
    0.0 (0.00 to 0.00)
    5.5 (1.22 to 9.79)
    6.4 (1.80 to 10.93)
    0.9 (0.00 to 2.68)
    9.9 (4.35 to 15.47)
    6.3 (0.00 to 13.10)
    6.0 (0.00 to 12.58)
    No statistical analyses for this end point

    Secondary: Change from Baseline in Simplified Disease Activity Index (SDAI)

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    End point title
    Change from Baseline in Simplified Disease Activity Index (SDAI)
    End point description
    Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity
    End point type
    Secondary
    End point timeframe
    Baseline, Days 7, 14, 28, 56 and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -5.36 ± 7.86
    -6.48 ± 8.87
    -6.99 ± 10.49
    -4.75 ± 13.25
    -10.86 ± 9.33
    -8.73 ± 11.21
    -5.37 ± 9.49
        Week 2 Day 14
    -6.50 ± 10.54
    -10.46 ± 10.97
    -11.44 ± 10.85
    -7.54 ± 13.74
    -14.39 ± 10.99
    -9.84 ± 12.29
    -8.13 ± 11.01
        Week 4 Day 28
    -10.53 ± 11.03
    -14.47 ± 12.41
    -14.21 ± 12.20
    -8.92 ± 15.17
    -18.87 ± 11.20
    -12.13 ± 11.13
    -7.74 ± 12.02
        Week 8 Day 56
    -15.25 ± 10.41
    -18.95 ± 13.80
    -18.97 ± 13.91
    -15.74 ± 16.18
    -22.62 ± 11.97
    -18.57 ± 12.80
    -7.82 ± 11.20
        Week 12 Day 84
    -17.54 ± 11.36
    -22.89 ± 12.52
    -23.24 ± 12.50
    -17.47 ± 16.70
    -23.33 ± 11.97
    -21.97 ± 13.78
    -12.92 ± 12.61
    No statistical analyses for this end point

    Secondary: Percentage of Participants Meeting the SDAI-based Remission Criteria

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    End point title
    Percentage of Participants Meeting the SDAI-based Remission Criteria
    End point description
    The SDAI was the numerical sum of five outcome parameter: SJC and TJC (based on a 28-joint assessment), PGA and MDG (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. The SDAI =< 3.3 indicates disease remission
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Percentage of participants
    number (confidence interval 95%)
        Week 1 Day 7
    0.00 (0.00 to 0.00)
    0.9 (0.00 to 2.71)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
        Week 2 Day 14
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
    1.8 (0.00 to 4.28)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
        Week 4 Day 28
    0.00 (0.00 to 0.00)
    0.9 (0.00 to 2.71)
    0.9 (0.00 to 2.68)
    0.00 (0.00 to 0.00)
    4.5 (0.65 to 8.36)
    2.1 (0.00 to 6.12)
    0.00 (0.00 to 0.00)
        Week 8 Day 56
    0.00 (0.00 to 0.00)
    2.8 (0.00 to 5.82)
    3.6 (0.14 to 7.13)
    0.00 (0.00 to 0.00)
    6.3 (1.78 to 10.83)
    0.00 (0.00 to 0.00)
    0.00 (0.00 to 0.00)
        Week 12 Day 84
    0.00 (0.00 to 0.00)
    4.6 (0.66 to 8.51)
    6.4 (1.80 to 10.93)
    0.9 (0.00 to 2.68)
    9.0 (3.68 to 14.34)
    6.3 (0.00 to 13.10)
    6.0 (0.00 to 12.58)
    No statistical analyses for this end point

    Secondary: Change from Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components

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    End point title
    Change from Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components
    End point description
    The 36-Item Short Form Health Survey (SF-36) is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health.
    End point type
    Secondary
    End point timeframe
    Day 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Number on a scale
    arithmetic mean (standard deviation)
        Physical component score change:baseline-week 12
    5.57 ± 5.98
    5.71 ± 6.85
    6.59 ± 7.54
    3.54 ± 6.81
    6.41 ± 6.43
    5.35 ± 7.48
    1.75 ± 6.39
        Mental component score change:baseline-week 12
    7.04 ± 9.32
    4.89 ± 10.57
    6.92 ± 12.06
    4.29 ± 10.51
    6.50 ± 10.79
    5.76 ± 10.22
    5.11 ± 10.10
    No statistical analyses for this end point

    Secondary: Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score

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    End point title
    Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
    End point description
    The FACIT Fatigue questionnaire consists of 13 statements designed to measure the degree of fatigue experience by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3(quite a bit), 4 (very much). Statement 1 to 6 and 9 to 13 are worded so that higher scores correspond to greater fatigue, while statements 7 and 8 are worded so that higher scores correspond to less fatigue.
    End point type
    Secondary
    End point timeframe
    Day 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
        arithmetic mean (standard deviation)
    9.00 ± 10.57
    8.21 ± 10.22
    8.95 ± 10.04
    7.08 ± 10.88
    9.59 ± 9.02
    8.85 ± 9.57
    5.71 ± 9.24
    No statistical analyses for this end point

    Secondary: Change from Baseline in Tender/Painful Joint Count (68 Joint Count)

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    End point title
    Change from Baseline in Tender/Painful Joint Count (68 Joint Count)
    End point description
    Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness.
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -2.79 ± 7.25
    -4.12 ± 8.14
    -3.33 ± 9.27
    -3.81 ± 10.85
    -5.58 ± 9.41
    -6.57 ± 8.66
    -3.06 ± 11.01
        Week 2 Day 19
    -4.33 ± 12.31
    -6.36 ± 10.88
    -5.91 ± 9.38
    -5.78 ± 11.50
    -8.62 ± 10.46
    -6.08 ± 8.53
    -3.92 ± 10.77
        Week 4 Day 28
    -6.00 ± 8.89
    -7.90 ± 11.28
    -6.84 ± 9.53
    -7.55 ± 12.97
    -11.61 ± 11.43
    -7.79 ± 7.93
    -4.40 ± 12.37
        Week 8 Day 56
    -9.72 ± 8.20
    -11.57 ± 12.18
    -9.75 ± 10.93
    -10.75 ± 14.37
    -14.12 ± 11.33
    -11.65 ± 10.34
    -4.60 ± 12.41
        Week 12 Day 84
    -10.33 ± 9.40
    -12.72 ± 12.05
    -11.49 ± 11.15
    -10.55 ± 14.37
    -15.49 ± 12.31
    -13.73 ± 12.81
    -7.14 ± 13.32
    No statistical analyses for this end point

    Secondary: Change from Baseline in Swollen Joint Count (66 Joint Count)

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    End point title
    Change from Baseline in Swollen Joint Count (66 Joint Count)
    End point description
    Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -3.45 ± 6.02
    -2.89 ± 5.01
    -1.84 ± 5.19
    -3.35 ± 9.38
    -3.94 ± 5.33
    -3.45 ± 4.90
    -1.49 ± 4.49
        Week 2 Day 14
    -5.06 ± 5.14
    -4.78 ± 5.99
    -3.95 ± 6.44
    -4.23 ± 9.88
    -6.26 ± 5.98
    -3.29 ± 5.69
    -2.96 ± 6.27
        Week 4 Day 28
    -5.95 ± 6.09
    -6.33 ± 7.98
    -4.38 ± 4.55
    -5.47 ± 9.26
    -8.50 ± 6.39
    -4.21 ± 6.39
    -3.46 ± 5.62
        Week 8 Day 56
    -7.72 ± 7.44
    -8.06 ± 8.13
    -6.54 ± 5.78
    -7.41 ± 10.82
    -9.60 ± 6.94
    -6.81 ± 6.16
    -3.02 ± 7.76
        Week 12 Day 84
    -8.48 ± 7.01
    -8.89 ± 8.23
    -7.36 ± 5.88
    -8.26 ± 11.48
    -9.94 ± 6.91
    -7.65 ± 6.75
    -4.86 ± 5.84
    No statistical analyses for this end point

    Secondary: Change from Baseline in Patient Assessment Score of Arthritis Pain

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    End point title
    Change from Baseline in Patient Assessment Score of Arthritis Pain
    End point description
    Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -9.00 ± 18.66
    -9.20 ± 20.56
    -11.18 ± 21.64
    -4.12 ± 22.43
    -15.75 ± 18.71
    -11.94 ± 21.25
    -2.76 ± 18.24
        Week 2 Day 14
    -6.08 ± 21.64
    -12.16 ± 20.09
    -17.08 ± 23.46
    -8.22 ± 25.72
    -18.13 ± 17.71
    -15.08 ± 21.87
    -4.72 ± 17.64
        Week 4 Day 28
    -13.41 ± 16.79
    -15.75 ± 21.97
    -18.63 ± 24.87
    -10.08 ± 27.16
    -20.21 ± 21.97
    -16.64 ± 27.86
    -7.54 ± 23.80
        Week 8 Day 56
    -18.38 ± 19.35
    -23.21 ± 22.10
    -25.95 ± 27.50
    -16.37 ± 27.65
    -24.70 ± 22.23
    -21.21 ± 27.13
    -7.13 ± 25.73
        Week 12 Day 84
    -23.14 ± 21.14
    -26.48 ± 23.30
    -30.63 ± 28.49
    -17.88 ± 29.42
    -26.30 ± 23.87
    -26.49 ± 27.65
    -13.98 ± 25.32
    No statistical analyses for this end point

    Secondary: Change from Baseline in Patient Global Assessment Score of Arthritis Pain

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    End point title
    Change from Baseline in Patient Global Assessment Score of Arthritis Pain
    End point description
    PGA is the patient’s global assessment of disease activity (on a 0-10 scale)
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -9.00 ± 15.88
    -10.30 ± 20.82
    -11.82 ± 22.52
    -3.07 ± 20.83
    -18.33 ± 20.81
    -13.15 ± 22.17
    -4.96 ± 19.18
        Week 2 Day 14
    -5.50 ± 20.98
    -13.70 ± 19.63
    -14.84 ± 24.08
    -5.39 ± 26.13
    -18.94 ± 22.33
    -15.46 ± 21.67
    -8.64 ± 19.43
        Week 4 Day 28
    -12.11 ± 16.68
    16.10 ± 23.48
    -17.75 ± 22.73
    -6.36 ± 25.99
    -21.78 ± 25.53
    -18.26 ± 27.53
    -10.96 ± 21.54
        Week 8 Day 56
    -19.19 ± 16.88
    -24.06 ± 24.99
    -22.59 ± 26.81
    -14.19 ± 29.80
    -26.77 ± 25.80
    -21.17 ± 25.98
    -11.82 ± 21.66
        Week 12 Day 84
    -23.33 ± 22.03
    -26.67 ± 26.89
    -27.33 ± 27.33
    -16.87 ± 28.68
    -26.24 ± 27.02
    -25.55 ± 27.52
    -13.80 ± 22.17
    No statistical analyses for this end point

    Secondary: Change from Baseline in Physician's Global Assessment Score of Arthritis

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    End point title
    Change from Baseline in Physician's Global Assessment Score of Arthritis
    End point description
    MDG is physician global assessment of disease activity (on a 0-10 scale).
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -7.89 ± 13.16
    -10.68 ± 15.41
    -12.82 ± 17.03
    -5.85 ± 15.44
    -14.23 ± 16.13
    -9.57 ± 17.10
    -7.66 ± 18.33
        Week 2 Day 14
    -11.10 ± 15.65
    -15.86 ± 16.77
    -18.30 ± 19.04
    -9.01 ± 18.07
    -21.33 ± 19.61
    -14.23 ± 18.50
    -9.85 ± 17.55
        Week 4 Day 28
    -16.89 ± 19.06
    -22.02 ± 18.61
    -20.92 ± 17.71
    -14.01 ± 21.03
    -28.81 ± 19.34
    -17.70 ± 20.49
    -12.73 ± 20.42
        Week 8 Day 56
    -24.59 ± 15.06
    -28.52 ± 21.11
    -29.67 ± 20.01
    -20.87 ± 23.85
    -36.16 ± 21.82
    -22.40 ± 20.43
    -9.91 ± 19.67
        Week 12 Day 84
    -26.81 ± 16.20
    -32.43 ± 19.24
    -34.48 ± 19.49
    -23.19 ± 23.39
    -37.18 ± 21.02
    -30.82 ± 21.95
    -18.44 ± 21.86
    No statistical analyses for this end point

    Secondary: Change from Baseline in C-Reactive Protein (CRP) Levels

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    End point title
    Change from Baseline in C-Reactive Protein (CRP) Levels
    End point description
    C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL)
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: (ng/mL) nanograms per milliliter
    arithmetic mean (standard deviation)
        Week 1 Day 7
    0.14 ± 2.09
    0.30 ± 2.58
    0.22 ± 2.49
    0.01 ± 1.29
    -1.21 ± 2.37
    -0.12 ± 2.60
    -0.10 ± 1.76
        Week 2 Day 14
    0.27 ± 1.78
    -0.10 ± 1.92
    -0.21 ± 2.29
    -0.12 ± 1.53
    -0.93 ± 2.70
    -0.20 ± 2.38
    -0.25 ± 2.60
        Week 4 Day 28
    0.15 ± 2.45
    -0.25 ± 2.55
    -0.44 ± 2.30
    0.14 ± 2.00
    -1.11 ± 2.17
    -0.30 ± 2.58
    -0.24 ± 2.80
        Week 8 Day 56
    -0.49 ± 1.66
    -0.52 ± 1.83
    -0.89 ± 3.16
    -0.39 ± 1.64
    -1.14 ± 2.39
    -1.19 ± 2.18
    -0.26 ± 2.55
        Week 12 Day 84
    -0.59 ± 1.43
    -0.77 ± 1.89
    -1.30 ± 2.88
    -0.45 ± 1.71
    -1.03 ± 2.01
    -1.55 ± 2.35
    -0.56 ± 2.75
    No statistical analyses for this end point

    Secondary: Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score

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    End point title
    Change from Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
    End point description
    Health Assessment Questionnaire – Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component
    End point type
    Secondary
    End point timeframe
    Days 7, 14, 28, 56, and 84
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Number of subjects analysed
    40
    109
    110
    110
    111
    48
    50
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 1 Day 7
    -0.20 ± 0.37
    -0.15 ± 0.35
    -0.22 ± 0.48
    -0.10 ± 0.38
    -0.26 ± 0.42
    -0.19 ± 0.36
    -0.14 ± 0.46
        Week 2 Day 14
    -0.24 ± 0.39
    -0.23 ± 0.46
    -0.28 ± 0.50
    -0.17 ± 0.45
    -0.35 ± 0.47
    -0.23 ± 0.45
    -0.13 ± 0.49
        Week 4 Day 28
    -0.34 ± 0.47
    -0.32 ± 0.48
    -0.40 ± 0.50
    -0.19 ± 0.56
    -0.50 ± 0.50
    -0.23 ± 0.42
    -0.17 ± 0.44
        Week 8 Day 56
    -0.49 ± 0.47
    -0.44 ± 0.56
    -0.56 ± 0.55
    -0.40 ± 0.64
    -0.60 ± 0.55
    -0.45 ± 0.50
    -0.23 ± 0.55
        Week 12 Day 84
    -0.51 ± 0.57
    -0.57 ± 0.57
    -0.65 ± 0.60
    -0.35 ± 0.68
    -0.65 ± 0.61
    -0.53 ± 0.61
    -0.30 ± 0.62
    No statistical analyses for this end point

    Secondary: Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss)

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    End point title
    Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss)
    End point description
    The Pharmacokinetics (PK) evaluation may include, but will not be limited to, plasma GDC-0853 concentrations and population PK model estimated PK exposures (area under the plasma concentration-time curve [AUC]. AUC was measured in Nanograms(ng) per millilitre(mL)*hour (hr)
    End point type
    Secondary
    End point timeframe
    Pre-dose (0 hours) up to 10 hours post-dose on Day 28
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 2: GDC-0853 High Dose
    Number of subjects analysed
    39
    106
    108
    48
    Units: Ng/mL*(hr)
        arithmetic mean (standard deviation)
    1170 ± 1600
    2910 ± 3180
    9380 ± 4860
    9890 ± 5480
    No statistical analyses for this end point

    Secondary: Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss)

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    End point title
    Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss)
    End point description
    Cmax is the maximum (peak) plasma concentration over the dosing interval at steady state (ss)
    End point type
    Secondary
    End point timeframe
    Pre-dose (0 hours) up to 10 hours post-dose on Day 28
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 2: GDC-0853 High Dose
    Number of subjects analysed
    39
    106
    108
    48
    Units: Nanogram per Milliliter (ng/mL)
        arithmetic mean (standard deviation)
    110 ± 116
    280 ± 223
    591 ± 282
    621 ± 302
    No statistical analyses for this end point

    Secondary: Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss)

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    End point title
    Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss)
    End point description
    Cmin is the minimum concentration over the dosing interval at steady state (ss)
    End point type
    Secondary
    End point timeframe
    Pre-dose (0 hours) up to 10 hours post-dose on Day 28
    End point values
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 2: GDC-0853 High Dose
    Number of subjects analysed
    39
    106
    108
    48
    Units: Nanogram per Milliliter (ng/mL)
        arithmetic mean (standard deviation)
    22.4 ± 41.0
    54.7 ± 83.4
    250 ± 146
    263 ± 170
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From randomization to end of study (approximately 22 months)
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 low dose, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 mid dose, orally twice daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 High Dose + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive GDC-0853 high dose, orally once daily along with placebo matched to adalimumab, subcutaneously every 2 weeks (Q2W) starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 milligrams per week (mg/week) (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
    Reporting group description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with placebo matched to adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 1: GDC-0853 Placebo + Adalimumab
    Reporting group description
    Participants of Cohort 1 will receive placebo matched to GDC-0853, orally once daily along with adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 High Dose
    Reporting group description
    Participants of Cohort 2 will receive GDC-0853 high dose, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Reporting group title
    Cohort 2: GDC-0853 Placebo
    Reporting group description
    Participants of Cohort 2 will receive placebo matched to GDC-0853, orally twice daily for 12 weeks. Participants will remain on a stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines) and folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.

    Serious adverse events
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 109 (0.92%)
    3 / 110 (2.73%)
    1 / 110 (0.91%)
    2 / 111 (1.80%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         number of deaths (all causes)
    0
    0
    1
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Cardiac disorders
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    1 / 110 (0.91%)
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    CHRONIC OBSTRUCTIVE PULMONARY DISEASE
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    0 / 110 (0.00%)
    1 / 110 (0.91%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PLEURAL EFFUSION
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    0 / 110 (0.00%)
    1 / 110 (0.91%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    SEIZURE
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    0 / 110 (0.00%)
    0 / 110 (0.00%)
    1 / 111 (0.90%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    SMALL INTESTINAL DISORDERS
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    0 / 110 (0.00%)
    0 / 110 (0.00%)
    1 / 111 (0.90%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    CELLULITS
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    1 / 110 (0.91%)
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 109 (0.92%)
    0 / 110 (0.00%)
    1 / 110 (0.91%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    PYELONEPHRITIS OBSTRUCTION
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    1 / 110 (0.91%)
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo Cohort 1: GDC-0853 High Dose + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Placebo Cohort 1: GDC-0853 Placebo + Adalimumab Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    9 / 40 (22.50%)
    18 / 109 (16.51%)
    11 / 110 (10.00%)
    15 / 110 (13.64%)
    16 / 111 (14.41%)
    3 / 49 (6.12%)
    7 / 49 (14.29%)
    Investigations
    ALANINE AMINOTRANFERASE INCREASED
         subjects affected / exposed
    2 / 40 (5.00%)
    5 / 109 (4.59%)
    4 / 110 (3.64%)
    1 / 110 (0.91%)
    1 / 111 (0.90%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    3
    5
    4
    1
    1
    0
    0
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    2 / 40 (5.00%)
    4 / 109 (3.67%)
    3 / 110 (2.73%)
    1 / 110 (0.91%)
    1 / 111 (0.90%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    2
    4
    4
    1
    1
    0
    0
    Nervous system disorders
    HEADACHE
         subjects affected / exposed
    2 / 40 (5.00%)
    4 / 109 (3.67%)
    5 / 110 (4.55%)
    5 / 110 (4.55%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    2
    5
    5
    5
    0
    0
    0
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 109 (0.00%)
    0 / 110 (0.00%)
    0 / 110 (0.00%)
    0 / 111 (0.00%)
    0 / 49 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    Gastrointestinal disorders
    NAUSEA
         subjects affected / exposed
    2 / 40 (5.00%)
    5 / 109 (4.59%)
    3 / 110 (2.73%)
    5 / 110 (4.55%)
    1 / 111 (0.90%)
    3 / 49 (6.12%)
    1 / 49 (2.04%)
         occurrences all number
    2
    5
    3
    6
    1
    4
    1
    VOMITING
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 109 (0.92%)
    0 / 110 (0.00%)
    0 / 110 (0.00%)
    1 / 111 (0.90%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    2
    1
    0
    0
    1
    0
    0
    Infections and infestations
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 40 (2.50%)
    3 / 109 (2.75%)
    3 / 110 (2.73%)
    2 / 110 (1.82%)
    6 / 111 (5.41%)
    0 / 49 (0.00%)
    0 / 49 (0.00%)
         occurrences all number
    1
    3
    3
    2
    6
    0
    0
    URINARY TRACT INFECTION
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 109 (1.83%)
    0 / 110 (0.00%)
    2 / 110 (1.82%)
    8 / 111 (7.21%)
    0 / 49 (0.00%)
    3 / 49 (6.12%)
         occurrences all number
    3
    3
    0
    2
    10
    0
    3

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Aug 2016
    The secondary efficacy objective to assess Boolean- and SDAI-based remission was clarified. Patients were excluded if treatment with methotrexate or folic acid was contraindicated. The timing of the planned interim analysis was clarified by specifying that the analysis was performed after 150 patients had completed the 12-week assessment.
    10 Mar 2017
    The initiation of Cohort 2 was no longer to be gated on the IA. The decision to open Cohort 2 was based on evidence for activity of BTK inhibition in patients with RA, as demonstrated by another BTK inhibitor.The population for Cohort 2 was broadened to also include those who may have had intolerance to 1 or 2 TNF inhibitors and who may have also had exposure to no more than one non-TNF inhibitor biologic. The size of Cohort 2 was expanded.

    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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