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Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02833350
Recruitment Status : Completed
First Posted : July 14, 2016
Results First Posted : September 10, 2019
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: GDC-0853
Drug: Adalimumab
Drug: Folic Acid
Drug: MTX
Drug: Placebo
Enrollment 578
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 Details  
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion. 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 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 investigators discretion. 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 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 investigators discretion. 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 investigators discretion. 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 investigators discretion. 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 investigators discretion. 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 investigators discretion.
Period Title: Overall Study
Started [1] 40 109 110 110 111 49 49
Randomized [2] 40 109 110 110 111 48 50
Completed 37 100 102 102 108 48 44
Not Completed 3 9 8 8 3 1 5
Reason Not Completed
Adverse Event             0             3             4             4             1             0             1
Death             0             0             1             0             0             0             0
Lack of Efficacy             0             2             1             4             0             1             1
Lost to Follow-up             0             1             0             0             0             0             1
Withdrawal by Subject             3             3             2             0             2             0             2
[1]
SAF population
[2]
ITT population
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion. 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 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 investigators discretion. 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 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 investigators discretion. 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 investigators discretion. 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 investigators discretion. 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 investigators discretion. 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 investigators discretion. Total of all reporting groups
Overall Number of Baseline Participants 40 109 110 110 111 49 49 578
Hide Baseline Analysis Population Description
Safety population (SAF) included all subjects that received treatment.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 109 participants 110 participants 110 participants 111 participants 49 participants 49 participants 578 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
35
  87.5%
95
  87.2%
99
  90.0%
98
  89.1%
98
  88.3%
41
  83.7%
40
  81.6%
506
  87.5%
>=65 years
5
  12.5%
14
  12.8%
11
  10.0%
12
  10.9%
13
  11.7%
8
  16.3%
9
  18.4%
72
  12.5%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 109 participants 110 participants 110 participants 111 participants 49 participants 49 participants 578 participants
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) 50.7  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 109 participants 110 participants 110 participants 111 participants 49 participants 49 participants 578 participants
Female
35
  87.5%
92
  84.4%
85
  77.3%
90
  81.8%
87
  78.4%
37
  75.5%
37
  75.5%
463
  80.1%
Male
5
  12.5%
17
  15.6%
25
  22.7%
20
  18.2%
24
  21.6%
12
  24.5%
12
  24.5%
115
  19.9%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 109 participants 110 participants 110 participants 111 participants 49 participants 49 participants 578 participants
American Indian or Alaska native
0
   0.0%
8
   7.3%
12
  10.9%
11
  10.0%
9
   8.1%
6
  12.2%
5
  10.2%
51
   8.8%
Asian
1
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
Black of African American
0
   0.0%
1
   0.9%
2
   1.8%
3
   2.7%
1
   0.9%
1
   2.0%
2
   4.1%
10
   1.7%
White
36
  90.0%
96
  88.1%
96
  87.3%
95
  86.4%
99
  89.2%
42
  85.7%
42
  85.7%
506
  87.5%
Multiple
3
   7.5%
2
   1.8%
0
   0.0%
1
   0.9%
1
   0.9%
0
   0.0%
0
   0.0%
7
   1.2%
Unknown
0
   0.0%
2
   1.8%
0
   0.0%
0
   0.0%
1
   0.9%
0
   0.0%
0
   0.0%
3
   0.5%
[1]
Measure Description: Race
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 109 participants 110 participants 110 participants 111 participants 49 participants 49 participants 578 participants
Hispanic or Latino
8
  20.0%
38
  34.9%
40
  36.4%
38
  34.5%
39
  35.1%
17
  34.7%
15
  30.6%
195
  33.7%
Not Hispanic or Latino
31
  77.5%
68
  62.4%
69
  62.7%
72
  65.5%
70
  63.1%
32
  65.3%
33
  67.3%
375
  64.9%
Not Stated
0
   0.0%
1
   0.9%
1
   0.9%
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.0%
3
   0.5%
Unknown
1
   2.5%
2
   1.8%
0
   0.0%
0
   0.0%
2
   1.8%
0
   0.0%
0
   0.0%
5
   0.9%
[1]
Measure Description: Ethnicity
1.Primary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1)
Hide 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].
Time Frame Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2503
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted difference
Estimated Value 8.00
Confidence Interval (2-Sided) 95%
-5.64 to 21.64
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0164
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted difference
Estimated Value 12.93
Confidence Interval (2-Sided) 95%
2.37 to 23.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted difference
Estimated Value 20.00
Confidence Interval (2-Sided) 95%
9.21 to 30.79
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Adverse Events
Hide 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.
Time Frame Day 1 up to 8 weeks after last dose (up to Week 20)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants according to treatment administered.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 49 49
Measure Type: Number
Unit of Measure: Percentage
37.5 42.2 50.9 45.5 45.0 22.4 44.9
3.Secondary Outcome
Title Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1)
Hide 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].
Time Frame Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1694
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted difference
Estimated Value -8.58
Confidence Interval (2-Sided) 95%
-20.82 to 3.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8132
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted difference
Estimated Value -1.50
Confidence Interval 95%
-13.96 to 10.95
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2)
Hide 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].
Time Frame Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title Cohort 2: GDC-0853 High Dose Cohort 2: GDC-0853 Placebo
Hide Arm/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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 48 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
25.0
(12.75 to 37.25)
12.0
(2.99 to 21.01)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0717
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Weighted difference
Estimated Value 13.7
Confidence Interval (2-Sided) 95%
-1.21 to 28.61
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
Hide 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]
Time Frame Days 7, 14, 28, 56, and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 48 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
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)
6.Secondary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
Hide 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].
Time Frame Days 7, 14, 28, 56, and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 48 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
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)
7.Secondary Outcome
Title Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
Hide 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].
Time Frame Days 7, 14, 28, 56, and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 48 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage
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)
0.00
(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
(0.00 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)
8.Secondary Outcome
Title Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Hide 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.
Time Frame Days 7, 14, 28, 56, and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 48 50
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Day 7 Number Analyzed 37 participants 106 participants 107 participants 109 participants 107 participants 47 participants 46 participants
-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 Number Analyzed 38 participants 106 participants 108 participants 110 participants 109 participants 48 participants 47 participants
-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 Number Analyzed 37 participants 103 participants 105 participants 105 participants 109 participants 47 participants 48 participants
-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 Number Analyzed 36 participants 100 participants 103 participants 100 participants 106 participants 47 participants 45 participants
-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 Number Analyzed 37 participants 97 participants 97 participants 102 participants 106 participants 47 participants 44 participants
-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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8504
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter adjusted difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.45 to 0.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments At week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9884
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.28 to 0.21
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1 Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9230
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.31 to 0.18
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9853
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.43 to 0.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6826
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.38 to 0.15
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2634
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.45 to 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2885
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.72 to 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0598
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-0.61 to 0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0440
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.62 to -0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4271
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.76 to 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0969
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.66 to 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0612
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.33
Confidence Interval (2-Sided) 95%
-0.68 to 0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2079
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.36
Confidence Interval (2-Sided) 95%
-0.84 to 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-0.92 to -0.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.57
Confidence Interval (2-Sided) 95%
-0.92 to -0.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.34 to 0.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.31 to 0.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.20 to 0.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0009
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.13 to 0.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.25 to 0.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.55
Confidence Interval (2-Sided) 95%
0.24 to 0.85
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0095
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.08 to 0.76
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0153
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.06 to 0.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4839
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.16 to 0.54
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5035
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-0.16 to 0.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4286
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.38 to 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1831
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.20
Confidence Interval (2-Sided) 95%
-0.50 to 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0667
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.65 to 0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.77
Confidence Interval (2-Sided) 95%
-1.11 to -0.42
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.76
Confidence Interval (2-Sided) 95%
-1.15 to -0.38
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
Hide 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.
Time Frame Days 7, 14, 28, 56, and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 48 50
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Day 7 Number Analyzed 37 participants 104 participants 102 participants 103 participants 104 participants 47 participants 45 participants
-0.43  (0.67) -0.48  (0.73) -0.49  (0.86) -0.37  (0.91) -1.10  (0.75) -0.63  (0.91) -.40  (0.69)
Week 2 Day 14 Number Analyzed 37 participants 103 participants 105 participants 105 participants 107 participants 48 participants 46 participants
-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 Number Analyzed 36 participants 101 participants 103 participants 99 participants 106 participants 47 participants 48 participants
-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 Number Analyzed 36 participants 99 participants 100 participants 97 participants 103 participants 47 participants 45 participants
-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 Number Analyzed 36 participants 94 participants 95 participants 99 participants 104 participants 47 participants 43 participants
-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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5807
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.18
Confidence Interval (2-Sided) 95%
-0.55 to 0.19
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6270
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.12
Confidence Interval (2-Sided) 95%
-0.39 to 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4475
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.42 to 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9891
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.47 to 0.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2244
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.21
Confidence Interval (2-Sided) 95%
-0.51 to 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0586
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.58 to 0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1338
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.85 to 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0119
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.40
Confidence Interval (2-Sided) 95%
-0.74 to -0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0046
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.44
Confidence Interval (2-Sided) 95%
-0.77 to -0.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3943
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.82 to 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0526
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-0.74 to 0.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0365
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.39
Confidence Interval (2-Sided) 95%
-0.76 to -0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1696
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.93 to 0.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.63
Confidence Interval (2-Sided) 95%
-1.01 to -0.25
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-1.00 to -0.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.37 to 0.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.34 to 0.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.21 to 0.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.14 to 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.25 to 0.91
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.21 to 0.87
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0084
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.09 to 0.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0124
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.07 to 0.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7565
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
-0.23 to 0.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7158
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
-0.22 to 0.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1368
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.22
Confidence Interval (2-Sided) 95%
-0.52 to 0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0974
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.28
Confidence Interval (2-Sided) 95%
-0.62 to 0.05
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0479
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.38
Confidence Interval (2-Sided) 95%
-0.76 to -0.00
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.84
Confidence Interval (2-Sided) 95%
-1.22 to -0.46
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.83
Confidence Interval (2-Sided) 95%
-1.24 to -0.42
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
Hide 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.
Time Frame Days 7, 14, 28, 56, and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 48 50
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Day 7 Number Analyzed 38 participants 105 participants 108 participants 110 participants 106 participants 47 participants 47 participants
-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 Number Analyzed 39 participants 105 participants 109 participants 110 participants 109 participants 47 participants 48 participants
-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 Number Analyzed 38 participants 104 participants 106 participants 108 participants 109 participants 47 participants 48 participants
-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 Number Analyzed 37 participants 100 participants 103 participants 102 participants 108 participants 47 participants 45 participants
-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 Number Analyzed 37 participants 97 participants 97 participants 102 participants 108 participants 47 participants 45 participants
-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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9193
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.41 to 0.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7062
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.10
Confidence Interval (2-Sided) 95%
-0.33 to 0.14
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8542
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.08
Confidence Interval (2-Sided) 95%
-0.31 to 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8095
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.51 to 0.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3862
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.17
Confidence Interval (2-Sided) 95%
-0.44 to 0.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4328
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.43 to 0.12
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4915
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.68 to 0.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1441
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.26
Confidence Interval (2-Sided) 95%
-0.58 to 0.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1890
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.24
Confidence Interval (2-Sided) 95%
-0.56 to 0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5566
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.25
Confidence Interval (2-Sided) 95%
-0.74 to -0.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0920
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.32
Confidence Interval (2-Sided) 95%
-0.68 to 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1391
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.65 to 0.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2873
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.86 to 0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.91 to -0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.54
Confidence Interval (2-Sided) 95%
-0.92 to -0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0050
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.07 to 0.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0020
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.10 to 0.57
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0082
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.07 to 0.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0056
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.08 to 0.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.19 to 0.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.21 to 0.84
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0650
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
-0.01 to 0.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0365
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.02 to 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9338
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.28 to 0.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Cohort 1: GDC-0853 High Dose + Adalimumab Placebo, Cohort 1: GDC-0853 Placebo + Adalimumab
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9520
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.29 to 0.46
Estimation Comments [Not Specified]
Hide Statistical Analysis 26
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 1, Day 7
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1496
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.45 to 0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 27
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 2, Day 14
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3936
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.43 to 0.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 28
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 4, Day 28
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0346
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.35
Confidence Interval (2-Sided) 95%
-0.68 to -0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 29
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 8, Day 56
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-1.04 to -0.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 30
Statistical Analysis Overview Comparison Group Selection Cohort 2: GDC-0853 High Dose, Cohort 2: GDC-0853 Placebo
Comments Week 12, Day 84
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Difference
Estimated Value -0.73
Confidence Interval (2-Sided) 95%
-1.11 to -0.34
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
Hide 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.
Time Frame Days 7, 14, 28, 56, and 84
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) All randomized participants who received any part of an infusion of study medication were included in the ITT analysis. Number of participants for whom data were collected is indicated for each time point.
Arm/Group Title 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
Hide Arm/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 are 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 investigators discretion.
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 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 investigators discretion.
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 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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
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 investigators discretion.
Overall Number of Participants Analyzed 40 109 110 110 111 48 50
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Week 1 Day 7 Number Analyzed 38 participants 103 participants 103 participants 104 participants 103 participants 47 participants 45 participants
-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 Number Analyzed 38 participants 102 participants 106 participants 105 participants 107 participants 47 participants 47 participants
-0.63  (0.98) -0.85