Clinical trial NCT02833350: Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-14
Enrollment: 578
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 1)
timeFrame: Day 84
measure: Percentage of Participants With Adverse Events
timeFrame: Day 1 up to 8 weeks after last dose (up to Week 20)
Secondary outcomes:
measure: Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Adalimumab (Cohort 1)
timeFrame: Day 84
measure: Percentage of Participants Achieving ACR50 Response at Day 84, Comparison Between GDC-0853 and Placebo (Cohort 2)
timeFrame: Day 84
measure: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response
timeFrame: Days 7, 14, 28, 56, and 84
measure: Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response
timeFrame: Days 7, 14, 28, 56, and 84
measure: Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change in Disease Activity Score From Baseline Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 [CRP])
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 [ESR])
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change in Disease Activity Score From Baseline Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])
timeFrame: Days 7, 14, 28, 56, and 84
measure: Percentage of Participants With DAS Low Disease Activity
timeFrame: Days 7, 14, 28, 56, and 84
measure: Percentage of Participants With DAS Remission
timeFrame: Days 7, 14, 28, 56, and 84
measure: Percentage of Participants Meeting the Boolean-based Remission Criteria
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in Clinical Disease Activity Index (CDAI)
timeFrame: Baseline, Days 7, 14, 28, 56 and 84
measure: Percentage of Participants Meeting the CDAI-based Remission Criteria
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in Simplified Disease Activity Index (SDAI)
timeFrame: Baseline, Days 7, 14, 28, 56 and 84
measure: Percentage of Participants Meeting the SDAI-based Remission Criteria
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components
timeFrame: Day 84
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score
timeFrame: Day 84
measure: Change From Baseline in Tender/Painful Joint Count (68 Joint Count)
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in Swollen Joint Count (66 Joint Count)
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in Patient Assessment Score of Arthritis Pain
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in Patient Global Assessment Score of Arthritis Pain
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in Physician's Global Assessment Score of Arthritis
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in C-Reactive Protein (CRP) Levels
timeFrame: Days 7, 14, 28, 56, and 84
measure: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
timeFrame: Days 7, 14, 28, 56, and 84
measure: Area Under the Concentration Time Curve From Time 0 to Time 24 of GDC-0853 at Steady State (AUC0-24,ss)
timeFrame: Pre-dose (0 hours) up to 10 hours post-dose on Day 28
measure: Maximum Observed Plasma Concentration of GDC-0853 at Steady State (Cmax,ss)
timeFrame: Pre-dose (0 hours) up to 10 hours post-dose on Day 28
measure: Minimum Observed Plasma Concentration of GDC-0853 at Steady State (Cmin,ss)
timeFrame: Pre-dose (0 hours) up to 10 hours post-dose on Day 28
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Pinnacle Research Group; Llc, Central
state: Alabama
city: Glendale
country: United States
facility: Arizona Arthritis & Rheumatology Associates, P.C.
state: Arizona
city: Covina
country: United States
facility: Medvin Clinical Research
state: California
city: El Cajon
country: United States
facility: TriWest Research Associates, LLC
state: California
city: Fullerton
country: United States
facility: Saint Jude Heritage Medical Grp
state: California
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Boca Raton
country: United States
facility: RASF-Clinical Research Center
state: Florida
city: Boynton Beach
country: United States
facility: ZASA Clinical Research
state: Florida
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Miami
country: United States
facility: InVentiv Health
state: Florida
city: Orlando
country: United States
facility: Omega Research Consultants
state: Florida
city: Tampa
country: United States
facility: McIlwain Medical Group
state: Florida
city: Idaho Falls
country: United States
facility: Institute of Arthritis Research
state: Idaho
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Greensboro
country: United States
facility: Medication Management
state: North Carolina
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading
state: Pennsylvania
city: Dallas
country: United States
facility: Metroplex Clinical Research
state: Texas
city: Dallas
country: United States
facility: Baylor Research Inst.
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Management - VO
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: Victoria
country: United States
facility: Crossroads Clinical Research, LLC
state: Texas
city: Danville
country: United States
facility: Danville Orthopedic Clinic, Inc.; Research Department
state: Virginia
city: Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Clinicas-Mar del Plata
city: Buenos Aires
country: Argentina
facility: Organizacion Medica de Investigacion
city: Buenos Aires
country: Argentina
facility: Hospital Italiano
city: Buenos Aires
country: Argentina
facility: APRILLUS
city: Buenos Aires
country: Argentina
facility: Instituto centenario
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Centro de Investigacion en Enfermedades Reumaticas CIER
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Expertia S.A- Mautalen Salud e Investigación
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: CCBR - Buenos Aires - AR; AxisMed SRL
city: Cordoba
country: Argentina
facility: ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas
city: La Plata
country: Argentina
facility: Hospital Italiano de La Plata
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Medicas Mar Del Plata
city: Quilmes
country: Argentina
facility: Instituto de Investigaciones Clínicas Quilmes
city: San Juan
country: Argentina
facility: CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica
city: San Miguel
country: Argentina
facility: Centro Medico Privado de Reumatologia; Reumathology
city: Goiânia
country: Brazil
facility: CIP - Centro Internacional de Pesquisa; Pesquisa Clinica
state: GO
city: Juiz de Fora
country: Brazil
facility: Centro Mineiro de Pesquisa - CMIP
state: MG
city: Curitiba
country: Brazil
facility: Edumed - Educação e Saúde SA
state: PR
city: Curtiba
country: Brazil
facility: Centro de Estudos em Terapias Inovadoras - CETI
state: PR
city: Rio de Janeiro
country: Brazil
facility: CCBR - Synarc Centro de Pesquisa Clinica - RJ
state: RJ
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo
state: RS
city: Porto Alegre
country: Brazil
facility: LMK Serviços Médicos S/S
state: RS
city: Campinas
country: Brazil
facility: CAEP - Centro Avancado de Estudos e Pesquisas Ltda.
state: SP
city: Santo Andre
country: Brazil
facility: Faculdade de Medicina do ABC - FMABC
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Pesquisa Clínica e Medicina Avançada Ltda
state: SP
city: São José do Rio Preto
country: Brazil
facility: Fundação Faculdade Regional de Medicina de São José do Rio Preto
state: SP
city: São Paulo
country: Brazil
facility: CPCLIN - Centro de Pesquisas Clínicas Ltda.; Pesquisa Clinica
state: SP
city: Dobrich
country: Bulgaria
facility: MHAT - Dobrich, AD
city: Plovdiv
country: Bulgaria
facility: MHAT "Eurohospital" - Plovdiv, OOD
city: Plovdiv
country: Bulgaria
facility: MHAT Kaspela; EOOD
city: Ruse
country: Bulgaria
facility: MHAT - Ruse, AD
city: Sevlievo
country: Bulgaria
facility: Medizinski Zentrar-1-Sevlievo EOOD
city: Sliven
country: Bulgaria
facility: MHAT "Hadzhi Dimitar", OOD
city: Sofia
country: Bulgaria
facility: Medical Center Excelsior OOD
city: Sofia
country: Bulgaria
facility: NMTH "Tsar Boris III"
city: Sofia
country: Bulgaria
facility: MHAT "Lyulin", EAD
city: Sofia
country: Bulgaria
facility: DCC "Alexandrovska", EOOD; Clinic of Neurology
city: Sofia
country: Bulgaria
facility: UMHAT "SofiaMed", OOD
city: Sofia
country: Bulgaria
facility: MC "Synexus - Sofia", EOOD
city: Stara Zagora
country: Bulgaria
facility: MHAT Dr. St. Kirkovich, AD
city: Vratsa
country: Bulgaria
facility: 'New Medical Center' , EOOD
city: Barranquilla
country: Colombia
facility: Centro de Reumatologia y Ortopedia
city: Bogota
country: Colombia
facility: Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM
city: Bogota
country: Colombia
facility: Riesgo de Fractura S.A.
city: Bogota
country: Colombia
facility: Fundación Instituto de Reumatología Fernando Chalem
city: Cali
country: Colombia
facility: Clinica de Artritis Temprana S.A.
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital; Department of Internal Medicine (Rheumatology)
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Suwon City
country: Korea, Republic of
facility: Ajou University Hospital
city: Cuernavaca
country: Mexico
facility: Consultorio Medico en Fundacion el Hospitalito de morelos A.C.
state: Morelos
city: Culiacán Rosales
country: Mexico
facility: Centro de Investigación de Tratamientos Innovadores de Sinaloa (CITI)
state: Sinaloa
city: Merida
country: Mexico
facility: Centro de Investigacion en Reumatologia
state: Yucatan
city: Cuernavaca
country: Mexico
facility: Consultorio Particular del Dr. Miguel Cortes Hernandez
city: Mexicali
country: Mexico
facility: Centro de Investigacion en Enfermedades Reumaticas y Osteoporosis
city: Mexico
country: Mexico
facility: Centro de Investigacion Clínica GRAMEL S.C
city: Queretaro
country: Mexico
facility: Policilinica Medica de Queretaro; Rheumatology
city: Tlalnepantla
country: Mexico
facility: Clinical Research Institute
city: Torreon
country: Mexico
facility: Unidad de Enfermedades Reumaticas y Cronicodegenerativas
city: Bialystok
country: Poland
facility: NZOZ OSTEO-MEDIC S.C. Artur Racewicz, Jerzy Supronik
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki; nr 2 im. Dr J. Biziela
city: Katowice
country: Poland
facility: Medica Pro Familia Spolka Akcyjna Oddzial w Katowicach
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Lodz
country: Poland
facility: CCBR - Lodz - PL
city: Olsztyn
country: Poland
facility: ETYKA Osrodek Badan Kliniczynch
city: Poznan
country: Poland
facility: Ai Centrum Medyczne Sp. Z O.O Sp.K.
city: Staszow
country: Poland
facility: KO-MED Centra Kliniczne Staszow
city: Warszawa
country: Poland
facility: Medycyna Kliniczna
city: Warszawa
country: Poland
facility: Centrum Medyczne AMED
city: Wrocław
country: Poland
facility: Wojewódzki Szpital Specjalistyczny we Wrocławiu
city: Zamosc
country: Poland
facility: KO-MED Centra Kliniczne Zamosc
city: Krasnoyarsk
country: Russian Federation
facility: TSBIH "Krasnoyarsk Interdistrict Clinical Hospital of Emergency Medical Care n.a. N.S. Karpovich
state: Krasnojarsk
city: Moscow
country: Russian Federation
facility: Federal State Budgetary Scientific Institution Research Institute of Rheumatology V.A. Nasonova
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: SBIH of Moscow "City Clinical Hospital # 1 n. a. N. I. Pirogov"
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: SBEI HPE " First Moscow State Medical University n.a. I.M. Sechenov" of the MoH of the RF
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: Technologii zdorovia LLC
state: Sankt Petersburg
city: Sankt-peterburg
country: Russian Federation
facility: Sanavita LLC
state: Sankt Petersburg
city: Sankt-peterburg
country: Russian Federation
facility: LLC Medical Sanitary Unit
state: Sankt Petersburg
city: Yekaterinburg
country: Russian Federation
facility: Center of Family Medicine LC
state: Sankt Petersburg
city: Yaroslavl
country: Russian Federation
facility: SBHI of Yaroslavl Region Clinical Hospital #3
state: Volgograd
city: Chelyabinsk
country: Russian Federation
facility: SMMIH "Chelyabinsk Regional Clinical Hospital"
state: Voronez
city: Kemerovo
country: Russian Federation
facility: SAHI of Kem. "Regional Clinical Hospital for War Veterans"
city: Korolev, Moscow Region
country: Russian Federation
facility: OOO Family Polyclinic
city: Moscow
country: Russian Federation
facility: Practical Medicine
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "Centre of Medical Common Practice"
city: Omsk
country: Russian Federation
facility: Ultramed
city: Saratov
country: Russian Federation
facility: SBEI HPE "Saratov State Medical University n.a. V. I. Razumovskiy" of the MoH of the RF
city: Smolensk
country: Russian Federation
facility: SBEI HPE "Smolensk State Medical University" of the MoH of the RF
city: St. Petersburg
country: Russian Federation
facility: City Hospital 25; Rheumatology
city: St. Petersburg
country: Russian Federation
facility: Pavlov First Saint Petersburg State Medical University
city: Tomsk
country: Russian Federation
facility: Siberian State Medical University
city: Ulyanovsk
country: Russian Federation
facility: SHI Ulyanovsk Reg Clinical Hospital
city: Vladivostok
country: Russian Federation
facility: Territorial Clinical Hospital #2
city: Yaroslavl
country: Russian Federation
facility: SHI Yaroslavl Regional Clinical Hospital
city: Belgrade
country: Serbia
facility: Institute of Rheumatology
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Niska Banja
country: Serbia
facility: Institute of Treatment and Rehabilitation "Niska Banja"
city: Novi Sad
country: Serbia
facility: Special hospital for rheumatic diseases Novi Sad
city: Sabac
country: Serbia
facility: General Hospital Sabac; Department of Urology and Hemodialysis
city: Ternopil
country: Ukraine
facility: CI of TRC
state: Kherson Governorate
city: Ivano-Frankivsk
country: Ukraine
facility: Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Medical Center Medical Clinic Blagomed LLC.
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Medical Center OK!Clinic+
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: SI NSС M.D. Strazhesko Institute of Cardiology of NAMSU
state: KIEV Governorate
city: Kyiv
country: Ukraine
facility: Clinic of Modern Rheumatology Revmotsentr LLC
state: KIEV Governorate
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital Dept of Rehmuaatology D. Halytskyi Lviv NMU
state: KIEV Governorate
city: Lviv
country: Ukraine
facility: CH of State Border Service of Ukraine (Military Base 2522); Dept of Therapy, D.Halytskyi Lviv NMU
state: KIEV Governorate
city: Uzhgorod
country: Ukraine
facility: A.Novak Transcarpathian Regional Clinical Hospital
state: KIEV Governorate
city: Dnipro
country: Ukraine
facility: Railway Transp DCH of HealthCenter Branch of PJSC Ukr Railway Dept of Rheumatology
state: Tavria Okruha
city: Kharkiv
country: Ukraine
facility: GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine
city: Kharkiv
country: Ukraine
facility: Kharkiv MA of PGE of MOHU Ch of Cardiology and Functional Diagnostics
city: Kyiv
country: Ukraine
facility: CNI Consultative and Diagnostic Center of Desnianskyi District of Kyiv
city: Kyiv
country: Ukraine
facility: MI of Helathcare Kyiv RCH P.L. Shupy NMA of PGE
city: Kyiv
country: Ukraine
facility: Gerontology Institute of the Ukrainian AMS
city: Kyiv
country: Ukraine
facility: Oleksandrivska Clinical Hospital
city: Lutsk
country: Ukraine
facility: Volyn Regional Center of Cardiovascular Pathology and Thrombolysis
city: Mykolaiv
country: Ukraine
facility: City Hospital #1
city: Poltava
country: Ukraine
facility: M.V. Sklifosovsky Poltava RCH Dept of Rheumatology HSEIU UMSA
city: Vinnytsia
country: Ukraine
facility: Private Small Enterprise Medical Center Pulse
city: Vinnytsia
country: Ukraine
facility: M.I. Pyrogov VRCH Dept of Gastroenterology M.I. Pyrogov VNMU
city: Zaporizhzhia
country: Ukraine
facility: City Clinical Hospital #9 Dept of Gastrosurgery SI Zaporizhzhia MA of PGE of MoHU
city: Zaporizhzhia
country: Ukraine
facility: CI City Hospital #7
city: Zaporizhzhia
country: Ukraine
facility: CI Zaporizhzhia Regional Clinical Hospital of ZRC
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: