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

Rheumatoid Arthritis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02833350
• Other study ID #: GA29350
• Secondary ID: 2016-000335-40
• Status: Completed
• Phase: Phase 2
• Start date: September 9, 2016
• Est. completion date: July 2, 2018

Study information

• Verified date: June 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multicenter, Phase II, randomized, double-blind, placebo-controlled, active comparator (Cohort 1 only), parallel-group, dose-ranging study to evaluate the efficacy and safety of GDC-0853 in participants with moderate to severe active RA and an inadequate response to previous methotrexate (MTX) therapy (Cohort 1) or MTX and tumor necrosis factor (TNF) therapy who may have also had exposure to no more than one non-TNF inhibitor biologic (Cohort 2).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 578
• Est. completion date: July 2, 2018
• Est. primary completion date: July 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Have a diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA

• RA disease activity by joint counts and laboratory markers of inflammation: greater than or equal to (>=) 6 tender/painful joints on motion (68 joint count) and >= 6 swollen joints (66 joint count) at both screening and Day 1 (randomization)

• For MTX-inadequate response (IR) participants: must have had an inadequate response to MTX

• For TNF-IR participants: must have had an inadequate response or intolerance to previous treatment with at least 1 and no more than 2 biologic TNF-alpha inhibitors and may have also been exposed to no more than one biologic non-TNF-alpha inhibitor

• High sensitivity C-reactive protein of >= 0.400 milligrams per deciliter (mg/dL) for Cohort 1 and >= 0.650 mg/dL for Cohort 2 at screening

Exclusion Criteria:

• History of or current inflammatory joint disease other than RA or other systemic autoimmune disorder

• For MTX-IR participants: History of treatment with any TNF inhibitor, including biosimilar equivalents and history of treatment with biologic non-TNF-alpha inhibitor for RA

• For all participants: Previous treatment with cell-depleting therapy including B cell-depleting therapy (e.g., anti-cluster of differentiation 20-directed therapy such as rituximab), tofacitinib, or other Janus kinase inhibitor(s), or alkylating agents

• Current treatment with medications that are well known to prolong the QT interval at doses that have a clinically meaningful effect on QT

• History of non-gallstone-related pancreatitis or chronic pancreatitis

• Evidence of serious uncontrolled concomitant cardiac, neurologic, pulmonary, renal, hepatic, endocrine, metabolic, or gastrointestinal disease

• Evidence of chronic and/or active hepatitis B or C

• Women who are pregnant, nursing (breast feeding), or intending to become pregnant during the study or within 60 days after completion of the study

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• GDC-0853
Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.
• Adalimumab
Participants will receive adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks.
• Folic Acid
Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.
• MTX
Participants will receive 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).
• Placebo
Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.

Locations

Country	Name	City	State
Argentina	APRILLUS	Buenos Aires
Argentina	Hospital Italiano	Buenos Aires
Argentina	Instituto centenario	Buenos Aires
Argentina	Instituto de Investigaciones Clinicas-Mar del Plata	Buenos Aires
Argentina	Organizacion Medica de Investigacion	Buenos Aires
Argentina	CCBR - Buenos Aires - AR; AxisMed SRL	Ciudad Autonoma Buenos Aires
Argentina	Centro de Investigacion en Enfermedades Reumaticas CIER	Ciudad Autonoma Buenos Aires
Argentina	Expertia S.A- Mautalen Salud e Investigación	Ciudad Autonoma Buenos Aires
Argentina	ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas	Cordoba
Argentina	Hospital Italiano de La Plata	La Plata
Argentina	Centro de Investigaciones Medicas Mar Del Plata	Mar del Plata
Argentina	Instituto de Investigaciones Clínicas Quilmes	Quilmes
Argentina	CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica	San Juan
Argentina	Centro Medico Privado de Reumatologia; Reumathology	San Miguel
Brazil	CAEP - Centro Avancado de Estudos e Pesquisas Ltda.	Campinas	SP
Brazil	Edumed - Educação e Saúde SA	Curitiba	PR
Brazil	Centro de Estudos em Terapias Inovadoras - CETI	Curtiba	PR
Brazil	CIP - Centro Internacional de Pesquisa; Pesquisa Clinica	Goiânia	GO
Brazil	Centro Mineiro de Pesquisa - CMIP	Juiz de Fora	MG
Brazil	Hospital Sao Vicente de Paulo	Passo Fundo	RS
Brazil	LMK Serviços Médicos S/S	Porto Alegre	RS
Brazil	CCBR - Synarc Centro de Pesquisa Clinica - RJ	Rio de Janeiro	RJ
Brazil	Faculdade de Medicina do ABC - FMABC	Santo Andre	SP
Brazil	Fundação Faculdade Regional de Medicina de São José do Rio Preto	São José do Rio Preto	SP
Brazil	Instituto de Pesquisa Clínica e Medicina Avançada Ltda	Sao Paulo	SP
Brazil	CPCLIN - Centro de Pesquisas Clínicas Ltda.; Pesquisa Clinica	São Paulo	SP
Bulgaria	MHAT - Dobrich, AD	Dobrich
Bulgaria	MHAT "Eurohospital" - Plovdiv, OOD	Plovdiv
Bulgaria	MHAT Kaspela; EOOD	Plovdiv
Bulgaria	MHAT - Ruse, AD	Ruse
Bulgaria	Medizinski Zentrar-1-Sevlievo EOOD	Sevlievo
Bulgaria	MHAT "Hadzhi Dimitar", OOD	Sliven
Bulgaria	DCC "Alexandrovska", EOOD; Clinic of Neurology	Sofia
Bulgaria	MC "Synexus - Sofia", EOOD	Sofia
Bulgaria	Medical Center Excelsior OOD	Sofia
Bulgaria	MHAT "Lyulin", EAD	Sofia
Bulgaria	NMTH "Tsar Boris III"	Sofia
Bulgaria	UMHAT "SofiaMed", OOD	Sofia
Bulgaria	MHAT Dr. St. Kirkovich, AD	Stara Zagora
Bulgaria	'New Medical Center' , EOOD	Vratsa
Colombia	Centro de Reumatologia y Ortopedia	Barranquilla
Colombia	Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM	Bogota
Colombia	Fundación Instituto de Reumatología Fernando Chalem	Bogota
Colombia	Riesgo de Fractura S.A.	Bogota
Colombia	Clinica de Artritis Temprana S.A.	Cali
Colombia	Hospital Pablo Tobon Uribe	Medellin
Korea, Republic of	Chungnam National University Hospital; Department of Internal Medicine (Rheumatology)	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Asan Medical Center - Oncology	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon City
Mexico	Consultorio Medico en Fundacion el Hospitalito de morelos A.C.	Cuernavaca	Morelos
Mexico	Consultorio Particular del Dr. Miguel Cortes Hernandez	Cuernavaca
Mexico	Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)	Culiacán Rosales	Sinaloa
Mexico	Centro de Investigacion en Reumatologia	Merida	Yucatan
Mexico	Centro de Investigacion en Enfermedades Reumaticas y Osteoporosis	Mexicali
Mexico	Centro de Investigacion Clínica GRAMEL S.C	Mexico
Mexico	Policilinica Medica de Queretaro; Rheumatology	Queretaro
Mexico	Clinical Research Institute	Tlalnepantla
Mexico	Unidad de Enfermedades Reumaticas y Cronicodegenerativas	Torreon
Poland	NZOZ OSTEO-MEDIC S.C. Artur Racewicz, Jerzy Supronik	Bialystok
Poland	Szpital Uniwersytecki; nr 2 im. Dr J. Biziela	Bydgoszcz
Poland	Medica Pro Familia Spolka Akcyjna Oddzial w Katowicach	Katowice
Poland	Centrum Medyczne Plejady	Krakow
Poland	CCBR - Lodz - PL	Lodz
Poland	ETYKA Osrodek Badan Kliniczynch	Olsztyn
Poland	Ai Centrum Medyczne Sp. Z O.O Sp.K.	Poznan
Poland	KO-MED Centra Kliniczne Staszow	Staszow
Poland	Centrum Medyczne AMED	Warszawa
Poland	Medycyna Kliniczna	Warszawa
Poland	Wojewódzki Szpital Specjalistyczny we Wroclawiu	Wroclaw
Poland	KO-MED Centra Kliniczne Zamosc	Zamosc
Russian Federation	SMMIH "Chelyabinsk Regional Clinical Hospital"	Chelyabinsk	Voronez
Russian Federation	SAHI of Kem. "Regional Clinical Hospital for War Veterans"	Kemerovo
Russian Federation	OOO Family Polyclinic	Korolev, Moscow Region
Russian Federation	TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich	Krasnoyarsk	Krasnojarsk
Russian Federation	Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova	Moscow	Moskovskaja Oblast
Russian Federation	Practical Medicine	Moscow
Russian Federation	SBEI HPE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF	Moscow	Moskovskaja Oblast
Russian Federation	SBIH of Moscow "City Clinical Hospital # 1 n. a. N. I. Pirogov"	Moscow	Moskovskaja Oblast
Russian Federation	Limited Liability Company "Centre of Medical Common Practice"	Novosibirsk
Russian Federation	Ultramed	Omsk
Russian Federation	LLC Medical Sanitary Unit	Sankt-peterburg	Sankt Petersburg
Russian Federation	Sanavita LLC	Sankt-peterburg	Sankt Petersburg
Russian Federation	Technologii zdorovia LLC	Sankt-peterburg	Sankt Petersburg
Russian Federation	SBEI HPE "Saratov State Medical University n.a. V. I. Razumovskiy" of the MoH of the RF	Saratov
Russian Federation	SBEI HPE "Smolensk State Medical University" of the MoH of the RF	Smolensk
Russian Federation	City Hospital 25; Rheumatology	St. Petersburg
Russian Federation	Pavlov First Saint Petersburg State Medical University	St. Petersburg
Russian Federation	Siberian State Medical University	Tomsk
Russian Federation	SHI Ulyanovsk Reg Clinical Hospital	Ulyanovsk
Russian Federation	Territorial Clinical Hospital #2	Vladivostok
Russian Federation	SBHI of Yaroslavl Region Clinical Hospital #3	Yaroslavl	Volgograd
Russian Federation	SHI Yaroslavl Regional Clinical Hospital	Yaroslavl
Russian Federation	Center of Family Medicine LC	Yekaterinburg	Sankt Petersburg
Serbia	Institute of Rheumatology	Belgrade
Serbia	Military Medical Academy	Belgrade
Serbia	Clinical Center Kragujevac	Kragujevac
Serbia	Institute of Treatment and Rehabilitation "Niska Banja"	Niska Banja
Serbia	Special hospital for rheumatic diseases Novi Sad	Novi Sad
Serbia	General Hospital Sabac; Department of Urology and Hemodialysis	Sabac
Ukraine	Railway Transp DCH of HealthCenter Branch of PJSC Ukr Railway Dept of Rheumatology	Dnipro	Tavria Okruha
Ukraine	Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU	Ivano-Frankivsk	KIEV Governorate
Ukraine	GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine	Kharkiv
Ukraine	Kharkiv MA of PGE of MOHU Ch of Cardiology and Functional Diagnostics	Kharkiv
Ukraine	Clinic of Modern Rheumatology Revmotsentr LLC	Kyiv	KIEV Governorate
Ukraine	CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv	Kyiv
Ukraine	Gerontology Institute of the Ukrainian AMS	Kyiv
Ukraine	Medical Center Medical Clinic Blagomed LLC.	Kyiv	KIEV Governorate
Ukraine	Medical Center OK!Clinic+	Kyiv	KIEV Governorate
Ukraine	MI of Helathcare Kyiv RCH P.L. Shupy NMA of PGE	Kyiv
Ukraine	Oleksandrivska Clinical Hospital	Kyiv
Ukraine	SI NS? M.D. Strazhesko Institute of Cardiology of NAMSU	Kyiv	KIEV Governorate
Ukraine	Volyn Regional Center of Cardiovascular Pathology and Thrombolysis	Lutsk
Ukraine	CH of State Border Service of Ukraine (Military Base 2522); Dept of Therapy, D.Halytskyi Lviv NMU	Lviv	KIEV Governorate
Ukraine	Lviv Regional Clinical Hospital Dept of Rehmuaatology D. Halytskyi Lviv NMU	Lviv	KIEV Governorate
Ukraine	City Hospital #1	Mykolaiv
Ukraine	M.V. Sklifosovsky Poltava RCH Dept of Rheumatology HSEIU UMSA	Poltava
Ukraine	CI of TRC	Ternopil	Kherson Governorate
Ukraine	A.Novak Transcarpathian Regional Clinical Hospital	Uzhgorod	KIEV Governorate
Ukraine	M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU	Vinnytsia
Ukraine	Private Small Enterprise Medical Center Pulse	Vinnytsia
Ukraine	CI City Hospital #7	Zaporizhzhia
Ukraine	CI Zaporizhzhia Regional Clinical Hospital of ZRC	Zaporizhzhia
Ukraine	City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU	Zaporizhzhia
United States	Pinnacle Research Group; Llc, Central	Anniston	Alabama
United States	RASF-Clinical Research Center	Boca Raton	Florida
United States	ZASA Clinical Research	Boynton Beach	Florida
United States	Clinical Research of West Florida	Clearwater	Florida
United States	Medvin Clinical Research	Covina	California
United States	Baylor Research Inst.	Dallas	Texas
United States	Metroplex Clinical Research	Dallas	Texas
United States	Danville Orthopedic Clinic, Inc.; Research Department	Danville	Virginia
United States	TriWest Research Associates, LLC	El Cajon	California
United States	Saint Jude Heritage Medical Grp	Fullerton	California
United States	Arizona Arthritis & Rheumatology Associates, P.C.	Glendale	Arizona
United States	Medication Management	Greensboro	North Carolina
United States	Accurate Clinical Management - VO	Houston	Texas
United States	Accurate Clinical Research	Houston	Texas
United States	Institute of Arthritis Research	Idaho Falls	Idaho
United States	Advanced Clinical Research	Meridian	Idaho
United States	InVentiv Health	Miami	Florida
United States	Omega Research Consultants	Orlando	Florida
United States	Oregon Health and Science University	Portland	Oregon
United States	Stanford University School of Medicine	Stanford	California
United States	McIlwain Medical Group	Tampa	Florida
United States	Crossroads Clinical Research, LLC	Victoria	Texas
United States	Clinical Research Center of Reading	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Colombia,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1)	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].	Day 84
Primary	Percentage of Participants With Adverse Events	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.	Day 1 up to 8 weeks after last dose (up to Week 20)
Secondary	Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1)	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].	Day 84
Secondary	Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2)	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].	Day 84
Secondary	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response	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]	Days 7, 14, 28, 56, and 84
Secondary	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response	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].	Days 7, 14, 28, 56, and 84
Secondary	Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response	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].	Days 7, 14, 28, 56, and 84
Secondary	Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])	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.	Days 7, 14, 28, 56, and 84
Secondary	Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])	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.	Days 7, 14, 28, 56, and 84
Secondary	Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])	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.	Days 7, 14, 28, 56, and 84
Secondary	Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])	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.	Days 7, 14, 28, 56, and 84
Secondary	Percentage of Participants With DAS Low Disease Activity	The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR) for a total possible score of 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDAS is defined as DAS28 = 3.2	Days 7, 14, 28, 56, and 84
Secondary	Percentage of Participants With DAS Remission	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	Days 7, 14, 28, 56, and 84
Secondary	Percentage of Participants Meeting the Boolean-based Remission Criteria	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).	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in Clinical Disease Activity Index (CDAI)	CDAI was derived as the sum of the following: tender joint count (TJC), swollen joint count (SJC), participant global assessment (PGA) of disease activity, and physician assessment of disease activity. TJC and SJC were taken as the number of tender and swollen joints, respectively, out of 28 assessed joints. PGA and physician assessment of disease activity were scored 0-100 millimeters (mm) and rounded to the nearest centimeter (cm) on a visual analog scale (VAS), where higher scores indicate greater perceived disease activity. The total CDAI score range was 0-76, where higher scores indicate increased disease activity. Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest. Negative values indicate improvement/reduction in RA disease activity.	Baseline, Days 7, 14, 28, 56 and 84
Secondary	Percentage of Participants Meeting the CDAI-based Remission Criteria	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.	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in Simplified Disease Activity Index (SDAI)	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	Baseline, Days 7, 14, 28, 56 and 84
Secondary	Percentage of Participants Meeting the SDAI-based Remission Criteria	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	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components	The 36-Item Short Form Health Survey (SF-36v2) is a questionnaire used to assess functional health and well-being and consists of eight domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health.; The SF-36v2 is summarized into Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. The PCS and MCS scores range from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.	Day 84
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score	The FACIT-Fatigue Scale consists of 13 items designed to measure the degree of fatigue experienced 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).; A total fatigue score is calculated by summing all items, and possible total scores range from 0 (maximum fatigue) to 52 (no fatigue). A positive change from baseline indicates an improvement in the patient's fatigue (less fatigue).	Day 84
Secondary	Change From Baseline in Tender/Painful Joint Count (68 Joint Count)	Tender Joint Count: a total of 68 joints will be assessed for tenderness. Each joint is assessed for the presence/absence of tenderness. 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68. A negative change from Baseline indicated improvement.	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in Swollen Joint Count (66 Joint Count)	Swollen Joint Count: a total of 66 joints will be assessed for swelling. Each joint is assessed for the presence/absence of swelling. 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66. A negative change from Baseline indicated improvement.	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in Patient Assessment Score of Arthritis Pain	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	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in Patient Global Assessment Score of Arthritis Pain	Participant-assessed arthritis pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of arthritis pain (0 mm=none; 100 mm=very severe). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change indicated a decrease in participant-assessed arthritis pain.	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in Physician's Global Assessment Score of Arthritis	Physician's assessment of participant's disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's assessment of the participant's disease activity (0 mm=very good; 100 mm=very poor). Change from baseline at a particular time point was calculated among patients with data available at both baseline and the time point of interest, where negative change from baseline indicated an improvement in physician-assessed disease activity.	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in C-Reactive Protein (CRP) Levels	C-reactive protein is a biological marker of inflammation and is measured in nanograms per milliliter (ng/mL)	Days 7, 14, 28, 56, and 84
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	The Stanford Health Assessment Questionnaire disability index is a patient-reported outcome used to assess difficulty in performing activities of daily living. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities.; To respond to each question, a four-level response with higher scores showing larger functional limitations, was chosen. Scoring is as follows with respect to performance of participant's everyday activities: 0 (equals)=without difficulties; 1= with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. The composite HAQ-DI score is the mean of the eight domain scores and the score ranges from 0 (no functional impairment) to 3 (maximum functional impairment). A negative change from baseline indicates improvement.	Days 7, 14, 28, 56, and 84
Secondary	Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss)	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)	Pre-dose (0 hours) up to 10 hours post-dose on Day 28
Secondary	Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss)	Cmax is the maximum (peak) plasma concentration over the dosing interval at steady state (ss)	Pre-dose (0 hours) up to 10 hours post-dose on Day 28
Secondary	Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss)	Cmin is the minimum concentration over the dosing interval at steady state (ss)	Pre-dose (0 hours) up to 10 hours post-dose on Day 28