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

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)

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).

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: GDC-0853; Drug: Folic Acid; Drug: MTX; Drug: Placebo; Drug: Adalimumab

• Study Type: Interventional
• Enrollment (Actual): 578
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1181ACH
    • Hospital Italiano
  • Buenos Aires, Argentina, C1015ABO
    • Organización Médica de Investigación
  • Buenos Aires, Argentina, B7600FZN
    • Instituto de Investigaciones Clinicas-Mar del Plata
  • Buenos Aires, Argentina, C1194AAO
    • APRILLUS
  • Buenos Aires, Argentina, C1204AAD
    • Instituto Centenario
  • Ciudad Autonoma Buenos Aires, Argentina, C1055AAF
    • Centro de Investigacion en Enfermedades Reumaticas CIER
  • Ciudad Autonoma Buenos Aires, Argentina, C1128AAE
    • Expertia S.A- Mautalén Salud e Investigación
  • Ciudad Autonoma Buenos Aires, Argentina, C1430CKE
    • CCBR - Buenos Aires - AR; AxisMed SRL
  • Cordoba, Argentina, X5000BNB
    • ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas
  • La Plata, Argentina, 1900
    • Hospital Italiano de La Plata
  • Mar del Plata, Argentina, B7600DHK
    • Centro de Investigaciones Medicas Mar del Plata
  • Quilmes, Argentina, 1878
    • Instituto de Investigaciones Clinicas Quilmes
  • San Juan, Argentina, 5400
    • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
  • San Miguel, Argentina, T4000AXL
    • Centro Medico Privado de Reumatologia; Reumathology
• Brazil
  • GO
    • Goiânia, GO, Brazil, 74110-120
      • CIP - Centro Internacional de Pesquisa; Pesquisa Clinica
  • MG
    • Juiz de Fora, MG, Brazil, 36036-330
      • Centro Mineiro de Pesquisa - CMiP
  • PR
    • Curitiba, PR, Brazil, 80440-080
      • Edumed - Educacao e Saude SA
    • Curtiba, PR, Brazil, 80030-110
      • Centro de Estudos em Terapias Inovadoras - CETI
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22271-100
      • CCBR - Synarc Centro de Pesquisa Clinica - RJ
  • RS
    • Passo Fundo, RS, Brazil, 99010-090
      • Hospital São Vicente de Paulo
    • Porto Alegre, RS, Brazil, 90480-000
      • LMK Serviços Médicos S/S
  • SP
    • Campinas, SP, Brazil, 13087-567
      • CAEP - Centro Avancado de Estudos e Pesquisas Ltda.
    • Santo Andre, SP, Brazil, 09060-650
      • Faculdade de Medicina do ABC - FMABC
    • Sao Paulo, SP, Brazil, 05437-010
      • Instituto de Pesquisa Clínica e Medicina Avançada Ltda
    • São José do Rio Preto, SP, Brazil, 15090-000
      • Fundação Faculdade Regional de Medicina de São José do Rio Preto
    • São Paulo, SP, Brazil, 01244-030
      • CPCLIN - Centro de Pesquisas Clínicas Ltda.; Pesquisa Clinica
• Bulgaria
  • Dobrich, Bulgaria, 9300
    • MHAT - Dobrich, AD
  • Plovdiv, Bulgaria, 4002
    • MHAT "Eurohospital" - Plovdiv, OOD
  • Plovdiv, Bulgaria, 4002
    • MHAT Kaspela; EOOD
  • Ruse, Bulgaria, 7002
    • MHAT - Ruse, AD
  • Sevlievo, Bulgaria, 5400
    • Medizinski Zentrar-1-Sevlievo EOOD
  • Sliven, Bulgaria, 8800
    • MHAT "Hadzhi Dimitar", OOD
  • Sofia, Bulgaria, 1233
    • NMTH "Tsar Boris III"
  • Sofia, Bulgaria, 1336
    • MHAT "Lyulin", EAD
  • Sofia, Bulgaria, 1000
    • Medical Center Excelsior OOD
  • Sofia, Bulgaria, 1431
    • DCC "Alexandrovska", EOOD; Clinic of Neurology
  • Sofia, Bulgaria, 1784
    • MC "Synexus - Sofia", EOOD
  • Sofia, Bulgaria, 1750
    • UMHAT "SofiaMed", OOD
  • Stara Zagora, Bulgaria, 6003
    • MHAT Dr. St. Kirkovich, AD
  • Vratsa, Bulgaria, 3000
    • 'New Medical Center' , EOOD
• Colombia
  • Barranquilla, Colombia, 80020
    • Centro de Reumatologia y Ortopedia
  • Bogota, Colombia, 110221
    • Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM
  • Bogota, Colombia, 110221
    • Riesgo de Fractura S.A.
  • Bogota, Colombia, 111211
    • Fundacion Instituto de Reumatologia Fernando Chalem
  • Cali, Colombia, 00000
    • Clinica de Artritis Temprana S.A.
  • Medellin, Colombia, 050034
    • Hospital Pablo Tobón Uribe
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35015
    • Chungnam National University Hospital; Department of Internal Medicine (Rheumatology)
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Gyeonggi-do, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05030
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - Oncology
  • Suwon City, Korea, Republic of, 443-721
    • Ajou University Hospital
• Mexico
  • Cuernavaca, Mexico, 62290
    • Consultorio Particular del Dr. Miguel Cortes Hernandez
  • Mexicali, Mexico, 21100
    • Centro de Investigacion en Enfermedades Reumaticas y Osteoporosis
  • Mexico, Mexico, 03720
    • Centro de Investigacion Clínica GRAMEL S.C
  • Queretaro, Mexico, 76000
    • Policilinica Medica de Queretaro; Rheumatology
  • Tlalnepantla, Mexico, 54055
    • Clinical Research Institute
  • Torreon, Mexico, 27000
    • Unidad de Enfermedades Reumaticas y Cronicodegenerativas
  • Morelos
    • Cuernavaca, Morelos, Mexico, 62170
      • Consultorio Medico en Fundacion el Hospitalito de morelos A.C.
  • Sinaloa
    • Culiacán Rosales, Sinaloa, Mexico, 80000
      • Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Centro de Investigacion en Reumatologia
• Poland
  • Bialystok, Poland, 15-351
    • NZOZ OSTEO-MEDIC S.C. Artur Racewicz, Jerzy Supronik
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki; nr 2 im. Dr J. Biziela
  • Katowice, Poland, 40-081
    • Medica Pro Familia Spolka Akcyjna Oddzial w Katowicach
  • Krakow, Poland, 30-349
    • Centrum Medyczne Plejady
  • Lodz, Poland, 90-368
    • CCBR - Lodz - PL
  • Olsztyn, Poland, 10-117
    • ETYKA Osrodek Badan Kliniczynch
  • Poznan, Poland, 61-113
    • Ai Centrum Medyczne Sp. Z O.O Sp.K.
  • Staszow, Poland, 28-200
    • KO-MED Centra Kliniczne Staszow
  • Warszawa, Poland, 00-660
    • Medycyna Kliniczna
  • Warszawa, Poland, 03-291
    • Centrum Medyczne AMED
  • Wrocław, Poland, 51-124
    • Wojewódzki Szpital Specjalistyczny we Wrocławiu
  • Zamosc, Poland, 22400
    • KO-MED Centra Kliniczne Zamosc
• Russian Federation
  • Kemerovo, Russian Federation, 650000
    • SAHI of Kem. "Regional Clinical Hospital for War Veterans"
  • Korolev, Moscow Region, Russian Federation, 141060
    • OOO Family Polyclinic
  • Moscow, Russian Federation, 115404
    • Practical Medicine
  • Novosibirsk, Russian Federation, 630091
    • Limited Liability Company "Centre of Medical Common Practice"
  • Omsk, Russian Federation, 644024
    • Ultramed
  • Saratov, Russian Federation, 410026
    • SBEI HPE "Saratov State Medical University n.a. V. I. Razumovskiy" of the MoH of the RF
  • Smolensk, Russian Federation, 214019
    • SBEI HPE "Smolensk State Medical University" of the MoH of the RF
  • St. Petersburg, Russian Federation, 197022
    • Pavlov First Saint Petersburg State Medical University
  • St. Petersburg, Russian Federation, 190068
    • City Hospital 25; Rheumatology
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University
  • Ulyanovsk, Russian Federation, 432063
    • SHI Ulyanovsk Reg Clinical Hospital
  • Vladivostok, Russian Federation, 690035
    • Territorial Clinical Hospital #2
  • Yaroslavl, Russian Federation, 150062
    • SHI Yaroslavl Regional Clinical Hospital
  • Krasnojarsk
    • Krasnoyarsk, Krasnojarsk, Russian Federation, 660062
      • TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich
  • Moskovskaja Oblast
    • Moscow, Moskovskaja Oblast, Russian Federation, 115522
      • Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova
    • Moscow, Moskovskaja Oblast, Russian Federation, 119049
      • SBIH of Moscow "City Clinical Hospital # 1 n. a. N. I. Pirogov"
    • Moscow, Moskovskaja Oblast, Russian Federation, 119992
      • SBEI HPE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF
  • Sankt Petersburg
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 195257
      • Sanavita LLC
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 196066
      • LLC Medical Sanitary Unit
    • Sankt-peterburg, Sankt Petersburg, Russian Federation, 191144
      • Technologii zdorovia LLC
    • Yekaterinburg, Sankt Petersburg, Russian Federation, 620043
      • Center of Family Medicine LC
  • Volgograd
    • Yaroslavl, Volgograd, Russian Federation, 150051
      • SBHI of Yaroslavl Region Clinical Hospital #3
  • Voronez
    • Chelyabinsk, Voronez, Russian Federation, 454076
      • SMMIH "Chelyabinsk Regional Clinical Hospital"
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Rheumatology
  • Belgrade, Serbia, 11040
    • Military Medical Academy
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Niska Banja, Serbia, 18205
    • Institute of Treatment and Rehabilitation "Niska Banja"
  • Novi Sad, Serbia, 21000
    • Special Hospital For Rheumatic Diseases Novi Sad
  • Sabac, Serbia, 15000
    • General Hospital Sabac; Department of Urology and Hemodialysis
• Ukraine
  • Kharkiv, Ukraine, 61039
    • GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
  • Kharkiv, Ukraine, 61176
    • Kharkiv MA of PGE of MOHU Ch of Cardiology and Functional Diagnostics
  • Kyiv, Ukraine, 02232
    • CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv
  • Kyiv, Ukraine, 04107
    • MI of Helathcare Kyiv RCH P.L. Shupy NMA of PGE
  • Kyiv, Ukraine, 04114
    • Gerontology Institute of the Ukrainian AMS
  • Kyiv, Ukraine, 1023
    • Oleksandrivska Clinical Hospital
  • Lutsk, Ukraine, 43024
    • Volyn Regional Center of Cardiovascular Pathology and Thrombolysis
  • Mykolaiv, Ukraine, 54003
    • City Hospital #1
  • Poltava, Ukraine, 36011
    • M.V. Sklifosovsky Poltava RCH Dept of Rheumatology HSEIU UMSA
  • Vinnytsia, Ukraine, 21018
    • M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
  • Vinnytsia, Ukraine, 21001
    • Private Small Enterprise Medical Center Pulse
  • Zaporizhzhia, Ukraine, 69118
    • CI City Hospital #7
  • Zaporizhzhia, Ukraine, 69600
    • CI Zaporizhzhia Regional Clinical Hospital of ZRC
  • Zaporizhzhia, Ukraine, 69096
    • City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU
  • KIEV Governorate
    • Ivano-Frankivsk, KIEV Governorate, Ukraine, 76008
      • Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU
    • Kyiv, KIEV Governorate, Ukraine, 03680
      • SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU
    • Kyiv, KIEV Governorate, Ukraine, 02091
      • Medical Center Ok!Clinic+
    • Kyiv, KIEV Governorate, Ukraine, 01601
      • Medical Center Medical Clinic Blagomed LLC.
    • Kyiv, KIEV Governorate, Ukraine, 04071
      • Clinic of Modern Rheumatology Revmotsentr LLC
    • Lviv, KIEV Governorate, Ukraine, 79010
      • Lviv Regional Clinical Hospital Dept of Rehmuaatology D. Halytskyi Lviv NMU
    • Lviv, KIEV Governorate, Ukraine, 79014
      • CH of State Border Service of Ukraine (Military Base 2522); Dept of Therapy, D.Halytskyi Lviv NMU
    • Uzhgorod, KIEV Governorate, Ukraine, 88018
      • A.Novak Transcarpathian Regional Clinical Hospital
  • Kherson Governorate
    • Ternopil, Kherson Governorate, Ukraine, 46002
      • CI of TRC
  • Tavria Okruha
    • Dnipro, Tavria Okruha, Ukraine, 49008
      • Railway Transp DCH of HealthCenter Branch of PJSC Ukr Railway Dept of Rheumatology
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group; Llc, Central
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Arizona Arthritis & Rheumatology Associates, P.C.
  • California
    • Covina, California, United States, 91723
      • Medvin Clinical Research
    • El Cajon, California, United States, 92020
      • TriWest Research Associates, LLC
    • Fullerton, California, United States, 92835
      • Saint Jude Heritage Medical Grp
    • Stanford, California, United States, 94305-5151
      • Stanford University School of Medicine
  • Florida
    • Boca Raton, Florida, United States, 33486
      • RASF-Clinical Research Center
    • Boynton Beach, Florida, United States, 33472
      • Zasa Clinical Research
    • Clearwater, Florida, United States, 33765
      • Clinical Research of West Florida
    • Miami, Florida, United States, 33136
      • InVentiv Health
    • Orlando, Florida, United States, 32810
      • Omega Research Consultants
    • Tampa, Florida, United States, 33613
      • McIlwain Medical Group
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Institute of Arthritis Research
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Medication Management
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Research Inst.
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research
    • Houston, Texas, United States, 77089
      • Accurate Clinical Research
    • Houston, Texas, United States, 77004
      • Accurate Clinical Management - VO
    • Victoria, Texas, United States, 77901
      • Crossroads Clinical Research, LLC
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Orthopedic Clinic, Inc.; Research Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: GDC-0853 High Dose + Adalimumab Placebo; 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.	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.; Other Names: RO7010939; Drug: 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.; Drug: 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).; Drug: 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.
Experimental: Cohort 1: GDC-0853 Low Dose + Adalimumab Placebo; 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.	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.; Other Names: RO7010939; Drug: 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.; Drug: 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).; Drug: 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.
Experimental: Cohort 1: GDC-0853 Mid Dose + Adalimumab Placebo; 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.	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.; Other Names: RO7010939; Drug: 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.; Drug: 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).; Drug: 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.
Active Comparator: Cohort 1: GDC-0853 Placebo + Adalimumab; 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.	Drug: 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.; Drug: 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).; Drug: 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.; Drug: Adalimumab; Participants will receive adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks.
Placebo Comparator: Cohort 1: GDC-0853 Placebo + Adalimumab Placebo; 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.	Drug: 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.; Drug: 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).; Drug: 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.
Experimental: Cohort 2: GDC-0853 High Dose; 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.	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.; Other Names: RO7010939; Drug: 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.; Drug: 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 Comparator: Cohort 2: GDC-0853 Placebo; 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.	Drug: 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.; Drug: 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).; Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2016
• Primary Completion (Actual): July 2, 2018
• Study Completion (Actual): July 2, 2018

Study Registration Dates

• First Submitted: July 12, 2016
• First Submitted That Met QC Criteria: July 12, 2016
• First Posted (Estimate): July 14, 2016

Study Record Updates

• Last Update Posted (Actual): June 12, 2020
• Last Update Submitted That Met QC Criteria: June 1, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Micronutrients; Vitamins; Vitamin B Complex; Hematinics; Adalimumab; Folic Acid
• Other Study ID Numbers: GA29350; 2016-000335-40 (EudraCT Number)