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

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

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

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

GA29350

ISRCTN number

US NCT number

NCT02833350

WHO universal trial number (UTN)

Sponsor organisation name

Hoffmann-La Roche AG

Sponsor organisation address

Grenzacherstrasse 124, Basel, Switzerland, CH-4070

Public contact

Hoffmann-La Roche AG, Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com

Scientific contact

Medical Communications, Hoffmann-La Roche AG, 41 616878333, globa.trial_information@roche.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

02 Jul 2018

Is this the analysis of the primary completion data?

Yes

Primary completion date

02 Jul 2018

Global end of trial reached?

Yes

Global end of trial date

02 Jul 2018

Was the trial ended prematurely?

Main objective of the trial

To evaluate the efficacy and safety of GDC-0853 in patients with moderate to severe active RA and an inadequate response to previous MTX therapy (Cohort 1) or MTX and TNF therapy who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form.

Background therapy

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

Evidence for comparator

Actual start date of recruitment

09 Sep 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 63

Country: Number of subjects enrolled

Brazil: 56

Country: Number of subjects enrolled

Bulgaria: 40

Country: Number of subjects enrolled

Colombia: 31

Country: Number of subjects enrolled

Mexico: 46

Country: Number of subjects enrolled

Russian Federation: 91

Country: Number of subjects enrolled

Serbia: 37

Country: Number of subjects enrolled

Ukraine: 154

Country: Number of subjects enrolled

United States: 27

Country: Number of subjects enrolled

Poland: 33

Worldwide total number of subjects

578

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

506

From 65 to 84 years

85 years and over

Subject disposition

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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.

Screening details

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

Period 1 title

Randomized

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo

Arm description

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

Arm type

Experimental

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

50 mg

Investigational medicinal product name

Adalimumab Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Adalimumab Placeb

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

150 MG

Cohort 1: GDC-0853 High Dose + Adalimumab Placebo

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Adalimumab Placeb

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg

Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Arm description

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

Arm type

Placebo

Investigational medicinal product name

GDC-0853 Placebo

Investigational medicinal product code

Other name

Fenebrutinib Placebo

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

N/A

Investigational medicinal product name

Adalimumab Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Cohort 1: GDC-0853 Placebo + Adalimumab

Arm description

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

Arm type

Active comparator

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

40 mg

Investigational medicinal product name

GDC-0853 Placebo

Investigational medicinal product code

Other name

GDC-0853 Placebo

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

N/A

Cohort 2: GDC-0853 High Dose

Arm description

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

Arm type

Experimental

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg

Cohort 2: GDC-0853 Placebo

Arm description

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

Arm type

Placebo

Investigational medicinal product name

GDC-0853 Placebo

Investigational medicinal product code

Other name

Fenebrutinib Placebo

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

N/A

Number of subjects in period 1	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Started	40	109	110	110	111	48	50
Completed	40	109	110	110	111	48	50

Period 2 title

Treated

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Adalimumab Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

50 mg

Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Adalimumab Placeb

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

150 MG

Cohort 1: GDC-0853 High Dose + Adalimumab Placebo

Arm description

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

Arm type

Experimental

Investigational medicinal product name

Adalimumab Placeb

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg

Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Arm description

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

Arm type

Placebo

Investigational medicinal product name

Adalimumab Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

N/A

Investigational medicinal product name

GDC-0853 Placebo

Investigational medicinal product code

Other name

Fenebrutinib Placebo

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

N/A

Cohort 1: GDC-0853 Placebo + Adalimumab

Arm description

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

Arm type

Active comparator

Investigational medicinal product name

GDC-0853 Placebo

Investigational medicinal product code

Other name

GDC-0853 Placebo

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

N/A

Investigational medicinal product name

Adalimumab

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

40 mg

Cohort 2: GDC-0853 High Dose

Arm description

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

Arm type

Experimental

Investigational medicinal product name

GDC-0853

Investigational medicinal product code

Other name

Fenebrutinib

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

200 mg

Cohort 2: GDC-0853 Placebo

Arm description

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

Arm type

Placebo

Investigational medicinal product name

GDC-0853 Placebo

Investigational medicinal product code

Other name

Fenebrutinib Placebo

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

N/A

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: This endpoint was specific for Cohort 1 only.

Number of subjects in period 2	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Started	40	109	110	110	111	49	49
Completed	37	100	102	102	108	48	44
Not completed	3	9	8	8	3	1	5
Adverse event, serious fatal	-	-	1	-	-	-	-
Consent withdrawn by subject	3	3	2	-	2	-	2
Adverse event, non-fatal	-	3	4	4	1	-	1
Lost to follow-up	-	1	-	-	-	-	1
Lack of efficacy	-	2	1	4	-	1	1

Baseline characteristics

Top of page

Reporting group title

Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 High Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab

Reporting group description

Reporting group title

Cohort 2: GDC-0853 High Dose

Reporting group description

Reporting group title

Cohort 2: GDC-0853 Placebo

Reporting group description

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

End points

Top of page

Reporting group title

Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 High Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab

Reporting group description

Reporting group title

Cohort 2: GDC-0853 High Dose

Reporting group description

Reporting group title

Cohort 2: GDC-0853 Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 High Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab

Reporting group description

Reporting group title

Cohort 2: GDC-0853 High Dose

Reporting group description

Reporting group title

Cohort 2: GDC-0853 Placebo

Reporting group description

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

Top of page

End point title

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

End point description

ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

End point type

Primary

End point timeframe

Day 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab
Number of subjects analysed	40	109	110	110	111
Units: Percentage
number (confidence interval 95%)	17.5 (5.72 to 29.28)	27.5 (19.14 to 35.91)	34.5 (25.66 to 43.43)	14.5 (7.96 to 21.13)	36.0 (27.10 to 44.97)

Week 12 Day 84

Comparison groups

Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo v Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Number of subjects included in analysis

150

Analysis specification

Pre-specified

Analysis type

P-value

= 0.2503

Method

Cochran-Mantel-Haenszel

Parameter type

Weighted difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-5.64

upper limit

21.64

Week 12 Day 84

Comparison groups

Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo v Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Number of subjects included in analysis

219

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0164

Method

Cochran-Mantel-Haenszel

Parameter type

Weighted difference

Point estimate

12.93

Confidence interval

level

95%

sides

2-sided

lower limit

2.37

upper limit

23.48

Week 12 Day 84

Comparison groups

Cohort 1: GDC-0853 High Dose + Adalimumab Placebo v Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Number of subjects included in analysis

220

Analysis specification

Pre-specified

Analysis type

P-value

= 0.0003

Method

Cochran-Mantel-Haenszel

Parameter type

Weighted difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

9.21

upper limit

30.79

Primary: Percentage of Participants With Adverse Events

Top of page

End point title

Percentage of Participants With Adverse Events ^[1]

End point description

An Adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE was any experience that suggested a significant hazard, contraindication, side effect or precaution that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. Safety population included all participants according to treatment administered.

End point type

Primary

End point timeframe

Day 1 up to 8 weeks after last dose (up to Week 20)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics are presented for this measure. No statistical analyses were planned.

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	49	49
Units: Percentage of participants
number (not applicable)	37.5	42.2	50.9	45.5	45.0	22.4	44.9

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Day 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab
Number of subjects analysed	40	109	110	110	111
Units: Percentage
number (confidence interval 95%)	17.5 (5.72 to 29.28)	27.5 (19.14 to 35.91)	34.5 (25.66 to 43.43)	14.5 (7.96 to 21.13)	36.0 (27.10 to 44.97)

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Day 84

End point values	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	48	50
Units: Percentage
number (confidence interval 95%)	25.0 (12.75 to 37.25)	12.0 (2.99 to 21.01)

No statistical analyses for this end point

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

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End point title

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

End point description

ACR20 response is defined as a ≥ 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate]

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage
number (confidence interval 95%)
Week 1 Day 7	10.0 (.70 to 19.3)	14.7 (8.04 to 21.32)	13.6 (7.22 to 20.05)	10.0 (4.39 to 15.61)	25.2 (17.15 to 33.30)	22.9 (11.03 to 34.81)	2.0 (0.00 to 5.88)
Week 2 Day 14	12.5 (2.25 to 22.75)	19.3 (11.86 to 26.67)	27.3 (18.95 to 35.60)	16.4 (9.45 to 23.28)	48.6 (39.35 to 57.95)	25.0 (12.75 to 37.25)	10.0 (1.68 to 18.32)
Week 4 Day 28	30.0 (15.80 to 44.20)	34.9 (25.92 to 43.81)	41.8 (32.60 to 51.04)	25.5 (17.31 to 33.59)	59.5 (50.33 to 68.59)	35.4 (21.89 to 48.95)	24.0 (12.16 to 35.84)
Week 8 Day 56	50.0 (34.51 to 65.49)	52.3 (42.92 to 61.67)	58.2 (48.96 to 67.40)	37.3 (28.24 to 46.31)	71.2 (62.74 to 79.60)	47.9 (33.78 to 62.05)	18.0 (7.35 to 28.65)
Week 12 Day 84	60.0 (44.82 to 75.18)	56.0 (46.64 to 65.28)	59.1 (49.90 to 68.28)	36.4 (27.37 to 45.35)	72.1 (63.73 to 80.42)	58.3 (44.39 to 72.28)	24.0 (12.16 to 35.84)

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage
number (confidence interval 95%)
Week 1 Day 7	2.5 (0.00 to 7.34)	2.8 (0.00 to 5.82)	3.6 (0.14 to 7.13)	2.7 (0.00 to 5.77)	4.5 (0.65 to 8.36)	6.3 (0.00 to 13.10)	2.0 (0.00 to 5.88)
Week 2 Day 14	0.0 (0.00 to 0.00)	1.8 (0.00 to 4.35)	7.3 (2.42 to 12.13)	2.7 (0.00 to 5.77)	9.0 (3.68 to 14.34)	10.4 (1.77 to 19.06)	0.00 (0.00 to 0.00)
Week 4 day 28	5.0 (0.00 to 11.75)	9.2 (3.76 to 14.59)	10.0 (4.39 to 15.61)	6.4 (1.80 to 10.93)	25.2 (17.15 to 33.30)	10.4 (1.77 to 19.06)	6.0 (0.00 to 12.58)
Week 8 Day 56	15.0 (3.93 to 26.07)	18.3 (11.08 to 25.62)	22.7 (14.9 to 30.56)	17.3 (10.21 to 24.34)	32.4 (23.72 to 41.14)	22.9 (11.03 to 34.81)	10.0 (1.68 to 18.32)
Week 12 Day 84	17.5 (5.72 to 29.28)	27.5 (19.14 to 35.91)	34.5 (25.66 to 43.43)	14.5 (7.96 to 21.13)	36.0 (27.10 to 44.97)	25.0 (12.75 to 37.25)	12.0 (2.99 to 21.01)

No statistical analyses for this end point

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

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End point title

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

End point description

ACR70 response is defined as a ≥ 70% improvement (reduction) compared with Baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage
number (confidence interval 95%)
Week 1 Day 7	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.71)	0.9 (0.00 to 2.68)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 2 Day 14	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.71)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	3.6 (0.14 to 7.07)	4.2 (0.00 to 9.82)	0.0 (0.00 to 0.00)
Week 4 Day 28	0.0 (0.00 to 0.00)	2.8 (0.00 to 5.82)	4.5 (0.65 to 8.44)	0.9 (0.00 to 2.68)	6.3 (1.78 to 10.83)	2.1 (0.00 to 6.12)	2.0 (0.00 to 5.88)
Week 8 Day 56	0.0 (0.00 to 0.00)	7.3 (2.44 to 12.24)	9.1 (3.72 to 14.46)	3.6 (0.14 to 7.13)	14.4 (7.88 to 20.95)	6.3 (0.00 to 13.10)	4.0 (0.00 to 9.43)
Week 12 Day 84	5.0 (0.00 to 11.75)	9.2 (3.76 to 14.59)	12.7 (6.50 to 18.96)	7.3 (2.42 to 12.13)	18.0 (10.87 to 25.17)	14.6 (4.60 to 24.57)	4.0 (0.00 to 9.43)

No statistical analyses for this end point

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

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End point title

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

End point description

The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score < 2.6.

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-0.34 ± 0.60	-0.35 ± 0.66	-0.37 ± 0.80	-0.33 ± 0.84	-0.92 ± 0.71	-0.49 ± 0.84	-0.36 ± 0.63
Week 2 Day 14	-0.47 ± 0.72	-0.63 ± 0.84	-0.70 ± 0.80	-.54 ± 0.90	-1.09 ± 0.81	-0.65 ± 0.87	-0.45 ± 0.69
Week 4 Day 28	-0.75 ± 0.86	-0.90 ± 0.96	-0.91 ± 0.97	-0.62 ± 1.04	-1.45 ± 0.87	-0.77 ± 0.90	-0.44 ± 0.84
Week 8 Day 56	-1.14 ± 0.90	-1.35 ± 1.12	-1.37 ± 1.11	-1.08 ± 1.19	-1.75 ± 0.98	-1.33 ± 0.98	-0.56 ± 0.87
Week 12 Day 84	-1.30 ± 0.95	-1.72 ± 1.11	-1.70 ± 1.02	-1.17 ± 1.24	-1.87 ± 1.02	-1.62 ± 1.15	-0.86 ± 1.03

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-0.43 ± 0.67	-0.48 ± 0.73	-0.49 ± 0.86	-0.37 ± 0.91	-1.10 ± 0.75	-0.63 ± 0.91	-0.40 ± 0.69
Week 2 Day 14	-0.51 ± 0.85	-0.77 ± 0.86	-0.84 ± 0.86	-0.57 ± 1.00	-1.26 ± 0.89	-0.81 ± 0.98	-0.54 ± 0.80
Week 4 Day 28	-0.88 ± 0.90	-1.06 ± 1.02	-1.08 ± 1.03	-0.65 ± 1.16	-1.61 ± 0.94	-0.95 ± 1.04	-0.55 ± 0.94
Week 8 Day 56	-1.31 ± 0.91	-1.56 ± 1.21	-1.57 ± 1.16	-1.20 ± 1.30	-1.97 ± 1.03	-1.51 ± 1.05	-0.67 ± 1.01
Week 12 Day 84	-1.53 ± 0.95	-1.97 ± 1.20	-1.93 ± 1.11	-1.33 ± 1.33	-2.06 ± 1.08	-1.83 ± 1.22	-1.00 ± 1.11

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-0.35 ± 0.57	-0.42 ± 0.65	-0.39 ± 0.68	-0.34 ± 0.86	-0.72 ± 0.72	-0.50 ± 0.73	-0.31 ± 0.60
Week 2 Day 14	-0.60 ± 0.89	-0.69 ± 0.84	-0.68 ± 0.74	-0.55 ± 0.92	-1.02 ± 0.84	-0.64 ± 0.81	-0.51 ± 0.73
Week 4 Day 28	-0.88 ± 0.89	-0.99 ± 0.98	-0.97 ± 0.90	-0.75 ± 1.02	-1.47 ± 1.02	-0.85 ± 0.81	-0.50 ± 0.83
Week 8 Day 56	-1.25 ± 0.85	-1.44 ± 1.14	-1.40 ± 1.06	-1.15 ± 1.19	-1.74 ± 0.98	-1.35 ± 0.96	-0.70 ± 0.98
Week 12 Day 84	-1.51 ± 1.01	-1.80 ± 1.25	-1.80 ± 0.99	-1.30 ± 1.22	-1.85 ± 1.06	-1.65 ± 1.06	-0.94 ± 10.6

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-0.45 ± 0.63	-0.54 ± 0.72	-0.52 ± 0.77	-0.37 ± 0.95	-0.93 ± 0.76	-0.65 ± 0.80	-0.36 ± 0.66
Week 2 Day 14	-0.63 ± 0.98	-0.85 ± 0.85	-0.84 ± 0.82	-0.58 ± 1.03	-1.22 ± 0.94	-0.81 ± 0.92	-0.60 ± 0.84
Week 4 Day 28	-1.00 ± 0.95	-1.16 ± 1.06	-1.15 ± 0.98	-0.79 ± 1.16	-1.65 ± 1.11	-1.04 ± 0.95	-0.61 ± 0.96
Week 8 Day 56	-1.43 ± 0.88	-1.67 ± 1.25	-1.63 ± 1.14	-1.29 ± 1.31	-2.00 ± 1.06	-1.54 ± 1.04	-0.81 ± 1.12
Week 12 Day 84	-1.76 ± 1.04	-2.06 ± 1.36	-2.05 ± 1.08	-1.46 ± 1.32	-2.08 ± 1.14	-1.89 ± 1.15	-1.08 ± 1.17

No statistical analyses for this end point

Secondary: Percentage of Participants with DAS low Disease Activity

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End point title

Percentage of Participants with DAS low Disease Activity

End point description

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage of participants
number (confidence interval 95%)
Week 1 Day 7	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.71)	1.8 (0.00 to 4.31)	0.0 (0.00 to 0.00)	1.8 (0.00 to 4.28)	2.1 (0.00 to 6.12)	0.00 (0.00 to 0.00)
Week 2 day 14	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	1.8 (0.00 to 4.31)	0.9 (0.00 to 2.68)	4.5 (0.65 to 8.36)	2.1 (0.00 to 6.12)	2.0 (0.00 to 5.88)
Week 4 Day 28	0.0 (0.00 to 0.00)	1.8 (0.00 to 4.35)	6.4 (1.80 to 10.93)	1.8 (0.00 to 4.31)	11.7 (5.73 to 17.69)	2.1 (0.00 to 6.12)	0.0 (0.00 to 0.00)
Week 8 Day 56	0.0 (0.00 to 0.00)	8.3 (3.09 to 13.42)	11.8 (5.79 to 17.85)	3.6 (0.14 to 7.13)	18.0 (10.87 to 25.17)	2.1 (0.00 to 6.12)	2.0 (0.00 to 5.88)
Week 12 Day 84	7.5 (0.00 to 15.66)	19.3 (11.86 to 26.67)	14.5 (7.86 to 21.13)	3.6 (0.14 to 7.13)	17.1 (10.11 to 24.12)	14.6 (4.60 to 24.57)	4.0 (0.00 to 9.43)

No statistical analyses for this end point

Secondary: Percentage of Participants with DAS Remission

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End point title

Percentage of Participants with DAS Remission

End point description

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage of participants
number (confidence interval 95%)
Week 1 Day 7	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	2.1 (0.00 to 6.12)	0.0 (0.00 to 0.00)
Week 2 Day 14	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.68)	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.66)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 4 Day 28	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	1.8 (0.00 to 4.31)	0.9 (0.00 to 2.68)	4.5 (0.65 to 8.36)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 8 Day 56	0.0 (0.00 to 0.00)	3.7 (0.14 to 7.20)	4.5 (0.65 to 8.44)	1.8 (0.00 to 4.31)	9.0 (3.68 to 14.34)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 12 Day 84	2.5 (0.00 to 7.34)	7.3 (2.44 to 12.24)	8.2 (3.06 to 13.30)	3.6 (0.14 to 7.13)	9.0 (3.68 to 14.34)	4.2 (0.00 to 9.82)	4.0 (0.00 to 9.43)

No statistical analyses for this end point

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

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End point title

Percentage of Participants Meeting the Boolean-based Remission Criteria

End point description

Boolean Remission is defined as Tender joint count less than 1, Swollen joint count less than 1, CRP less than 1 mg/dL, patient global assessment less than 1 (on 0 to 10 VAS scale).

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage of participants
number (confidence interval 95%)
Week 1 Day 7	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.76)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 2 Day 14	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 4 Day 28	0.0 (0.00 to 0.00)	1.0 (0.00 to 2.81)	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.73)	2.8 (0.00 to 5.82)	2.1 (0.00 to 6.25)	0.0 (0.00 to 0.00)
Week 8 Day 56	0.0 (0.00 to 0.00)	2.0 (0.00 to 4.70)	1.90 (0.00 to 4.56)	1.0 (0.00 to 2.86)	3.7 (0.14 to 7.20)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 12 Day 84	0.0 (0.00 to 0.00)	2.0 (0.00 to 4.84)	4.1 (0.17 to 8.08)	1.0 (0.00 to 2.89)	6.5 (1.84 to 11.12)	8.5 (0.53 to 16.49)	0.0 (0.00 to 6.53)

No statistical analyses for this end point

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

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End point title

Change from Baseline in Clinical Disease Activity Index (CDAI)

End point description

Clinical Disease Activity Index is defined as CDAI= : SJC(28) + TJC(28) + PGA + MDG where TJC and SJC are the tender and swollen joint counts from 28 joints, PGA is the patient’s global assessment of disease activity (on a 0-10 scale) and MDG is physician global assessment of disease activity (on a 0-10 scale). The cutoff value for CDAI remission is <=2.8

End point type

Secondary

End point timeframe

Baseline, Days 7, 14, 28, 56 and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-5.45 ± 7.69	-6.70 ± 8.26	-7.40 ± 9.97	-4.71 ± 12.91	-9.64 ± 8.93	-8.61 ± 10.67	-5.26 ± 9.79
Week 2 Day 14	-6.85 ± 11.10	-10.33 ± 10.45	-11.33 ± 10.47	-7.44 ± 13.39	-13.44 ± 10.52	-9.64 ± 12.17	-7.70 ± 10.64
Week 4 Day 28	-10.36 ± 10.88	13.84 ± 12.11	-13.78 ± 11.46	-9.43 ± 14.77	-17.74 ± 10.84	-11.83 ± 11.08	-7.49 ± 11.46
Week 8 Day 56	-14.76 ± 10.04	-18.61 ± 13.48	-18.10 ± 12.99	-15.49 ± 15.74	-21.36 ± 11.69	-17.38 ± 12.39	-7.57 ± 10.51
Week 12 Day 84	-16.99 ± 11.21	-22.05 ± 12.19	-22.10 ± 11.83	-17.02 ± 16.24	-22.22 ± 11.76	-20.42 ± 13.20	-12.23 ± 12.06

No statistical analyses for this end point

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

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End point title

Percentage of Participants Meeting the CDAI-based Remission Criteria

End point description

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage of participants
number (confidence interval 95%)
Week 1 Day 7	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.71)	0.9 (0.00 to 2.68)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 2 Day 14	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)	0.0 (0.0 to 0.00)	0.0 (0.00 to 0.00)	1.8 (0.00 to 4.28)	0.0 (0.00 to 0.00)	0.0 (0.00 to 0.00)
Week 4 Day 28	0.0 (0.00 to 0.00)	0.9 (0.00 to 2.71)	0.9 (0.00 to 2.68)	0.0 (0.00 to 0.00)	4.5 (0.65 to 8.36)	2.1 (0.0 to 6.12)	0.0 (0.00 to 0.00)
Week 8 Day 56	0.00 (0.0 to 0.00)	2.8 (0.0 to 5.82)	5.5 (1.21 to 9.70)	0.0 (0.00 to 0.00)	7.2 (2.40 to 12.02)	4.2 (0.00 to 9.82)	0.0 (0.00 to 0.00)
Week 12 Day 84	0.0 (0.00 to 0.00)	5.5 (1.22 to 9.79)	6.4 (1.80 to 10.93)	0.9 (0.00 to 2.68)	9.9 (4.35 to 15.47)	6.3 (0.00 to 13.10)	6.0 (0.00 to 12.58)

No statistical analyses for this end point

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

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End point title

Change from Baseline in Simplified Disease Activity Index (SDAI)

End point description

Simplified Disease Activity Index (SDAI) is the numerical sum of five outcome parameters: TJC and SJC (based on a 28-joint assessment), PtGA and PhGA (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. SDAI total score ranges from 0 (no disease activity) to 86 (maximal disease activity), where higher scores represents higher disease activity. The SDAI =< 3.3 indicates disease remission, > 3.4 to 11 indicates low disease activity, > 11 to 26 indicates moderate disease activity, and > 26 indicates high disease activity

End point type

Secondary

End point timeframe

Baseline, Days 7, 14, 28, 56 and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-5.36 ± 7.86	-6.48 ± 8.87	-6.99 ± 10.49	-4.75 ± 13.25	-10.86 ± 9.33	-8.73 ± 11.21	-5.37 ± 9.49
Week 2 Day 14	-6.50 ± 10.54	-10.46 ± 10.97	-11.44 ± 10.85	-7.54 ± 13.74	-14.39 ± 10.99	-9.84 ± 12.29	-8.13 ± 11.01
Week 4 Day 28	-10.53 ± 11.03	-14.47 ± 12.41	-14.21 ± 12.20	-8.92 ± 15.17	-18.87 ± 11.20	-12.13 ± 11.13	-7.74 ± 12.02
Week 8 Day 56	-15.25 ± 10.41	-18.95 ± 13.80	-18.97 ± 13.91	-15.74 ± 16.18	-22.62 ± 11.97	-18.57 ± 12.80	-7.82 ± 11.20
Week 12 Day 84	-17.54 ± 11.36	-22.89 ± 12.52	-23.24 ± 12.50	-17.47 ± 16.70	-23.33 ± 11.97	-21.97 ± 13.78	-12.92 ± 12.61

No statistical analyses for this end point

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

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End point title

Percentage of Participants Meeting the SDAI-based Remission Criteria

End point description

The SDAI was the numerical sum of five outcome parameter: SJC and TJC (based on a 28-joint assessment), PGA and MDG (based on 0-10 cm VAS, where 0 = no disease activity and 10 = worst disease activity), and CRP. The SDAI =< 3.3 indicates disease remission

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Percentage of participants
number (confidence interval 95%)
Week 1 Day 7	0.00 (0.00 to 0.00)	0.9 (0.00 to 2.71)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)
Week 2 Day 14	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)	1.8 (0.00 to 4.28)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)
Week 4 Day 28	0.00 (0.00 to 0.00)	0.9 (0.00 to 2.71)	0.9 (0.00 to 2.68)	0.00 (0.00 to 0.00)	4.5 (0.65 to 8.36)	2.1 (0.00 to 6.12)	0.00 (0.00 to 0.00)
Week 8 Day 56	0.00 (0.00 to 0.00)	2.8 (0.00 to 5.82)	3.6 (0.14 to 7.13)	0.00 (0.00 to 0.00)	6.3 (1.78 to 10.83)	0.00 (0.00 to 0.00)	0.00 (0.00 to 0.00)
Week 12 Day 84	0.00 (0.00 to 0.00)	4.6 (0.66 to 8.51)	6.4 (1.80 to 10.93)	0.9 (0.00 to 2.68)	9.0 (3.68 to 14.34)	6.3 (0.00 to 13.10)	6.0 (0.00 to 12.58)

No statistical analyses for this end point

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

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End point title

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

End point description

The 36-Item Short Form Health Survey (SF-36) is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health.

End point type

Secondary

End point timeframe

Day 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Number on a scale
arithmetic mean (standard deviation)
Physical component score change:baseline-week 12	5.57 ± 5.98	5.71 ± 6.85	6.59 ± 7.54	3.54 ± 6.81	6.41 ± 6.43	5.35 ± 7.48	1.75 ± 6.39
Mental component score change:baseline-week 12	7.04 ± 9.32	4.89 ± 10.57	6.92 ± 12.06	4.29 ± 10.51	6.50 ± 10.79	5.76 ± 10.22	5.11 ± 10.10

No statistical analyses for this end point

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

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End point title

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

End point description

The FACIT Fatigue questionnaire consists of 13 statements designed to measure the degree of fatigue experience by the patient in the previous 7 days. For each question, there are five possible responses: 0 (not at all), 1 (a little bit), 2 (somewhat), 3(quite a bit), 4 (very much). Statement 1 to 6 and 9 to 13 are worded so that higher scores correspond to greater fatigue, while statements 7 and 8 are worded so that higher scores correspond to less fatigue.

End point type

Secondary

End point timeframe

Day 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)	9.00 ± 10.57	8.21 ± 10.22	8.95 ± 10.04	7.08 ± 10.88	9.59 ± 9.02	8.85 ± 9.57	5.71 ± 9.24

No statistical analyses for this end point

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

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End point title

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

End point description

Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness.

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-2.79 ± 7.25	-4.12 ± 8.14	-3.33 ± 9.27	-3.81 ± 10.85	-5.58 ± 9.41	-6.57 ± 8.66	-3.06 ± 11.01
Week 2 Day 19	-4.33 ± 12.31	-6.36 ± 10.88	-5.91 ± 9.38	-5.78 ± 11.50	-8.62 ± 10.46	-6.08 ± 8.53	-3.92 ± 10.77
Week 4 Day 28	-6.00 ± 8.89	-7.90 ± 11.28	-6.84 ± 9.53	-7.55 ± 12.97	-11.61 ± 11.43	-7.79 ± 7.93	-4.40 ± 12.37
Week 8 Day 56	-9.72 ± 8.20	-11.57 ± 12.18	-9.75 ± 10.93	-10.75 ± 14.37	-14.12 ± 11.33	-11.65 ± 10.34	-4.60 ± 12.41
Week 12 Day 84	-10.33 ± 9.40	-12.72 ± 12.05	-11.49 ± 11.15	-10.55 ± 14.37	-15.49 ± 12.31	-13.73 ± 12.81	-7.14 ± 13.32

No statistical analyses for this end point

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

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End point title

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

End point description

Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-3.45 ± 6.02	-2.89 ± 5.01	-1.84 ± 5.19	-3.35 ± 9.38	-3.94 ± 5.33	-3.45 ± 4.90	-1.49 ± 4.49
Week 2 Day 14	-5.06 ± 5.14	-4.78 ± 5.99	-3.95 ± 6.44	-4.23 ± 9.88	-6.26 ± 5.98	-3.29 ± 5.69	-2.96 ± 6.27
Week 4 Day 28	-5.95 ± 6.09	-6.33 ± 7.98	-4.38 ± 4.55	-5.47 ± 9.26	-8.50 ± 6.39	-4.21 ± 6.39	-3.46 ± 5.62
Week 8 Day 56	-7.72 ± 7.44	-8.06 ± 8.13	-6.54 ± 5.78	-7.41 ± 10.82	-9.60 ± 6.94	-6.81 ± 6.16	-3.02 ± 7.76
Week 12 Day 84	-8.48 ± 7.01	-8.89 ± 8.23	-7.36 ± 5.88	-8.26 ± 11.48	-9.94 ± 6.91	-7.65 ± 6.75	-4.86 ± 5.84

No statistical analyses for this end point

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

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End point title

Change from Baseline in Patient Assessment Score of Arthritis Pain

End point description

Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-9.00 ± 18.66	-9.20 ± 20.56	-11.18 ± 21.64	-4.12 ± 22.43	-15.75 ± 18.71	-11.94 ± 21.25	-2.76 ± 18.24
Week 2 Day 14	-6.08 ± 21.64	-12.16 ± 20.09	-17.08 ± 23.46	-8.22 ± 25.72	-18.13 ± 17.71	-15.08 ± 21.87	-4.72 ± 17.64
Week 4 Day 28	-13.41 ± 16.79	-15.75 ± 21.97	-18.63 ± 24.87	-10.08 ± 27.16	-20.21 ± 21.97	-16.64 ± 27.86	-7.54 ± 23.80
Week 8 Day 56	-18.38 ± 19.35	-23.21 ± 22.10	-25.95 ± 27.50	-16.37 ± 27.65	-24.70 ± 22.23	-21.21 ± 27.13	-7.13 ± 25.73
Week 12 Day 84	-23.14 ± 21.14	-26.48 ± 23.30	-30.63 ± 28.49	-17.88 ± 29.42	-26.30 ± 23.87	-26.49 ± 27.65	-13.98 ± 25.32

No statistical analyses for this end point

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

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End point title

Change from Baseline in Patient Global Assessment Score of Arthritis Pain

End point description

PGA is the patient’s global assessment of disease activity (on a 0-10 scale)

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-9.00 ± 15.88	-10.30 ± 20.82	-11.82 ± 22.52	-3.07 ± 20.83	-18.33 ± 20.81	-13.15 ± 22.17	-4.96 ± 19.18
Week 2 Day 14	-5.50 ± 20.98	-13.70 ± 19.63	-14.84 ± 24.08	-5.39 ± 26.13	-18.94 ± 22.33	-15.46 ± 21.67	-8.64 ± 19.43
Week 4 Day 28	-12.11 ± 16.68	16.10 ± 23.48	-17.75 ± 22.73	-6.36 ± 25.99	-21.78 ± 25.53	-18.26 ± 27.53	-10.96 ± 21.54
Week 8 Day 56	-19.19 ± 16.88	-24.06 ± 24.99	-22.59 ± 26.81	-14.19 ± 29.80	-26.77 ± 25.80	-21.17 ± 25.98	-11.82 ± 21.66
Week 12 Day 84	-23.33 ± 22.03	-26.67 ± 26.89	-27.33 ± 27.33	-16.87 ± 28.68	-26.24 ± 27.02	-25.55 ± 27.52	-13.80 ± 22.17

No statistical analyses for this end point

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

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End point title

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

End point description

MDG is physician global assessment of disease activity (on a 0-10 scale).

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-7.89 ± 13.16	-10.68 ± 15.41	-12.82 ± 17.03	-5.85 ± 15.44	-14.23 ± 16.13	-9.57 ± 17.10	-7.66 ± 18.33
Week 2 Day 14	-11.10 ± 15.65	-15.86 ± 16.77	-18.30 ± 19.04	-9.01 ± 18.07	-21.33 ± 19.61	-14.23 ± 18.50	-9.85 ± 17.55
Week 4 Day 28	-16.89 ± 19.06	-22.02 ± 18.61	-20.92 ± 17.71	-14.01 ± 21.03	-28.81 ± 19.34	-17.70 ± 20.49	-12.73 ± 20.42
Week 8 Day 56	-24.59 ± 15.06	-28.52 ± 21.11	-29.67 ± 20.01	-20.87 ± 23.85	-36.16 ± 21.82	-22.40 ± 20.43	-9.91 ± 19.67
Week 12 Day 84	-26.81 ± 16.20	-32.43 ± 19.24	-34.48 ± 19.49	-23.19 ± 23.39	-37.18 ± 21.02	-30.82 ± 21.95	-18.44 ± 21.86

No statistical analyses for this end point

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

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End point title

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

End point description

C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL)

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: (ng/mL) nanograms per milliliter
arithmetic mean (standard deviation)
Week 1 Day 7	0.14 ± 2.09	0.30 ± 2.58	0.22 ± 2.49	0.01 ± 1.29	-1.21 ± 2.37	-0.12 ± 2.60	-0.10 ± 1.76
Week 2 Day 14	0.27 ± 1.78	-0.10 ± 1.92	-0.21 ± 2.29	-0.12 ± 1.53	-0.93 ± 2.70	-0.20 ± 2.38	-0.25 ± 2.60
Week 4 Day 28	0.15 ± 2.45	-0.25 ± 2.55	-0.44 ± 2.30	0.14 ± 2.00	-1.11 ± 2.17	-0.30 ± 2.58	-0.24 ± 2.80
Week 8 Day 56	-0.49 ± 1.66	-0.52 ± 1.83	-0.89 ± 3.16	-0.39 ± 1.64	-1.14 ± 2.39	-1.19 ± 2.18	-0.26 ± 2.55
Week 12 Day 84	-0.59 ± 1.43	-0.77 ± 1.89	-1.30 ± 2.88	-0.45 ± 1.71	-1.03 ± 2.01	-1.55 ± 2.35	-0.56 ± 2.75

No statistical analyses for this end point

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

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End point title

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

End point description

Health Assessment Questionnaire – Disability Index (HAQ-DI): The Stanford Health Assessment Questionnaire disability index is a patient reported questionnaire specific for RA. It consists of 20 questions referring to eight component

End point type

Secondary

End point timeframe

Days 7, 14, 28, 56, and 84

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Number of subjects analysed	40	109	110	110	111	48	50
Units: Score on a scale
arithmetic mean (standard deviation)
Week 1 Day 7	-0.20 ± 0.37	-0.15 ± 0.35	-0.22 ± 0.48	-0.10 ± 0.38	-0.26 ± 0.42	-0.19 ± 0.36	-0.14 ± 0.46
Week 2 Day 14	-0.24 ± 0.39	-0.23 ± 0.46	-0.28 ± 0.50	-0.17 ± 0.45	-0.35 ± 0.47	-0.23 ± 0.45	-0.13 ± 0.49
Week 4 Day 28	-0.34 ± 0.47	-0.32 ± 0.48	-0.40 ± 0.50	-0.19 ± 0.56	-0.50 ± 0.50	-0.23 ± 0.42	-0.17 ± 0.44
Week 8 Day 56	-0.49 ± 0.47	-0.44 ± 0.56	-0.56 ± 0.55	-0.40 ± 0.64	-0.60 ± 0.55	-0.45 ± 0.50	-0.23 ± 0.55
Week 12 Day 84	-0.51 ± 0.57	-0.57 ± 0.57	-0.65 ± 0.60	-0.35 ± 0.68	-0.65 ± 0.61	-0.53 ± 0.61	-0.30 ± 0.62

No statistical analyses for this end point

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

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End point title

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

End point description

The Pharmacokinetics (PK) evaluation may include, but will not be limited to, plasma GDC-0853 concentrations and population PK model estimated PK exposures (area under the plasma concentration-time curve [AUC]. AUC was measured in Nanograms(ng) per millilitre(mL)*hour (hr)

End point type

Secondary

End point timeframe

Pre-dose (0 hours) up to 10 hours post-dose on Day 28

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 2: GDC-0853 High Dose
Number of subjects analysed	39	106	108	48
Units: Ng/mL*(hr)
arithmetic mean (standard deviation)	1170 ± 1600	2910 ± 3180	9380 ± 4860	9890 ± 5480

No statistical analyses for this end point

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

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End point title

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

End point description

Cmax is the maximum (peak) plasma concentration over the dosing interval at steady state (ss)

End point type

Secondary

End point timeframe

Pre-dose (0 hours) up to 10 hours post-dose on Day 28

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 2: GDC-0853 High Dose
Number of subjects analysed	39	106	108	48
Units: Nanogram per Milliliter (ng/mL)
arithmetic mean (standard deviation)	110 ± 116	280 ± 223	591 ± 282	621 ± 302

No statistical analyses for this end point

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

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End point title

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

End point description

Cmin is the minimum concentration over the dosing interval at steady state (ss)

End point type

Secondary

End point timeframe

Pre-dose (0 hours) up to 10 hours post-dose on Day 28

End point values	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 2: GDC-0853 High Dose
Number of subjects analysed	39	106	108	48
Units: Nanogram per Milliliter (ng/mL)
arithmetic mean (standard deviation)	22.4 ± 41.0	54.7 ± 83.4	250 ± 146	263 ± 170

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From randomization to end of study (approximately 22 months)

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 High Dose + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab Placebo

Reporting group description

Reporting group title

Cohort 1: GDC-0853 Placebo + Adalimumab

Reporting group description

Reporting group title

Cohort 2: GDC-0853 High Dose

Reporting group description

Reporting group title

Cohort 2: GDC-0853 Placebo

Reporting group description

Serious adverse events	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 40 (0.00%)	1 / 109 (0.92%)	3 / 110 (2.73%)	1 / 110 (0.91%)	2 / 111 (1.80%)	0 / 49 (0.00%)	0 / 49 (0.00%)
number of deaths (all causes)	0	0	1	0	0	0	0
number of deaths resulting from adverse events
Cardiac disorders
MYOCARDIAL INFARCTION
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	1 / 110 (0.91%)	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
SEIZURE
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	0 / 110 (0.00%)	0 / 110 (0.00%)	1 / 111 (0.90%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
SMALL INTESTINAL DISORDERS
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	0 / 110 (0.00%)	0 / 110 (0.00%)	1 / 111 (0.90%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	0 / 110 (0.00%)	1 / 110 (0.91%)	0 / 111 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PLEURAL EFFUSION
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	0 / 110 (0.00%)	1 / 110 (0.91%)	0 / 111 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
CELLULITS
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	1 / 110 (0.91%)	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	0 / 40 (0.00%)	1 / 109 (0.92%)	0 / 110 (0.00%)	1 / 110 (0.91%)	0 / 111 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYELONEPHRITIS OBSTRUCTION
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	1 / 110 (0.91%)	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo	Cohort 1: GDC-0853 High Dose + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab Placebo	Cohort 1: GDC-0853 Placebo + Adalimumab	Cohort 2: GDC-0853 High Dose	Cohort 2: GDC-0853 Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 40 (22.50%)	18 / 109 (16.51%)	11 / 110 (10.00%)	15 / 110 (13.64%)	16 / 111 (14.41%)	3 / 49 (6.12%)	7 / 49 (14.29%)
Investigations
ALANINE AMINOTRANFERASE INCREASED
subjects affected / exposed	2 / 40 (5.00%)	5 / 109 (4.59%)	4 / 110 (3.64%)	1 / 110 (0.91%)	1 / 111 (0.90%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences all number	3	5	4	1	1	0	0
ASPARTATE AMINOTRANSFERASE INCREASED
subjects affected / exposed	2 / 40 (5.00%)	4 / 109 (3.67%)	3 / 110 (2.73%)	1 / 110 (0.91%)	1 / 111 (0.90%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences all number	2	4	4	1	1	0	0
Nervous system disorders
HEADACHE
subjects affected / exposed	2 / 40 (5.00%)	4 / 109 (3.67%)	5 / 110 (4.55%)	5 / 110 (4.55%)	0 / 111 (0.00%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences all number	2	5	5	5	0	0	0
Gastrointestinal disorders
NAUSEA
subjects affected / exposed	2 / 40 (5.00%)	5 / 109 (4.59%)	3 / 110 (2.73%)	5 / 110 (4.55%)	1 / 111 (0.90%)	3 / 49 (6.12%)	1 / 49 (2.04%)
occurrences all number	2	5	3	6	1	4	1
VOMITING
subjects affected / exposed	2 / 40 (5.00%)	1 / 109 (0.92%)	0 / 110 (0.00%)	0 / 110 (0.00%)	1 / 111 (0.90%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences all number	2	1	0	0	1	0	0
Psychiatric disorders
ANXIETY
subjects affected / exposed	0 / 40 (0.00%)	0 / 109 (0.00%)	0 / 110 (0.00%)	0 / 110 (0.00%)	0 / 111 (0.00%)	0 / 49 (0.00%)	3 / 49 (6.12%)
occurrences all number	0	0	0	0	0	0	3
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
subjects affected / exposed	1 / 40 (2.50%)	3 / 109 (2.75%)	3 / 110 (2.73%)	2 / 110 (1.82%)	6 / 111 (5.41%)	0 / 49 (0.00%)	0 / 49 (0.00%)
occurrences all number	1	3	3	2	6	0	0
URINARY TRACT INFECTION
subjects affected / exposed	2 / 40 (5.00%)	2 / 109 (1.83%)	0 / 110 (0.00%)	2 / 110 (1.82%)	8 / 111 (7.21%)	0 / 49 (0.00%)	3 / 49 (6.12%)
occurrences all number	3	3	0	2	10	0	3

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Were there any global substantial amendments to the protocol? Yes

05 Aug 2016

The secondary efficacy objective to assess Boolean- and SDAI-based remission was clarified. Patients were excluded if treatment with methotrexate or folic acid was contraindicated. The timing of the planned interim analysis was clarified by specifying that the analysis was performed after 150 patients had completed the 12-week assessment.

10 Mar 2017

The initiation of Cohort 2 was no longer to be gated on the IA. The decision to open Cohort 2 was based on evidence for activity of BTK inhibition in patients with RA, as demonstrated by another BTK inhibitor.The population for Cohort 2 was broadened to also include those who may have had intolerance to 1 or 2 TNF inhibitors and who may have also had exposure to no more than one non-TNF inhibitor biologic. The size of Cohort 2 was expanded.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

Primary: Percentage of Participants With Adverse Events

Primary: Percentage of Participants With Adverse Events

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Percentage of Participants with DAS low Disease Activity

Secondary: Percentage of Participants with DAS low Disease Activity

Secondary: Percentage of Participants with DAS Remission

Secondary: Percentage of Participants with DAS Remission

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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