Clinical trial NCT01888874: Dose-finding Study of GLPG0634 as add-on to Methotrexate in Active Rheumatoid Arthritis Participants (DARWIN1)
Official title: Randomized, Double-blind, Placebo-controlled, Multicenter, Phase IIb Dose Finding Study of GLPG0634 Administered for 24 Weeks in Combination With Methotrexate to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Methotrexate inadequate responders
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2013-06-28
Enrollment: 599
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Participants suffering from active rheumatoid arthritis despite continued treatment with methotrexate were evaluated for improvement of disease activity (efficacy) when taking GLPG0634 (3 different doses - 50 milligram \[mg\], 100 mg and 200 mg daily -, each evaluated as once daily \[QD\] and twice daily \[BID\] regimen) or matching placebo for 24 weeks.

•During the course of the study, patients were also examined for any side effects that could occur (safety and tolerability), and the amount of GLPG0634 present in the blood (Pharmacokinetics) as well as the effects of GLPG0634 on disease- and mechanism of action-related parameters in the blood (Pharmacodynamics) were determined. Also, the effects of different doses and dose regiments of GLPG0634 administration on participants' disability, fatigue, and quality of life were evaluated.

Detailed description: * Treatment duration was 24 weeks in total.
* However, at Week 12, participants on placebo who did not achieve a 20% improvement in swollen joint count(SJC66) and tender joint count (TJC68) were re-randomized (automatically via interactive voice/web response \[IXRS\]) to treatment to receive GLPG0634 100 mg QD or 50 mg BID doses in a blinded fashion, participants on 50 mg QD who had not achieved a 20% improvement in SJC66 and TJC68 were assigned to 100 mg QD and participants on 25 mg BID. who did not achieve a 20% improvement in SJC66 and TJC68 were assigned to 50 mg BID. All continued the study until Week 24.
* Participants in the other groups maintained their randomized treatment until Week 24.

Eligibility criteria: Inclusion Criteria:

* have a diagnosis of RA since at least 6 months and meeting the 2010 ACR/EULAR criteria of RA and ACR functional class I-III,
* have ≥6 swollen joints (from a 66 joint count) and ≥8 tender joints (from a 68 joint count) at Screening and at Baseline,
* Screening serum c-reactive protein ≥0.7 x upper limit of laboratory normal range (ULN),
* have received MTX for ≥6 months and have been on a stable dose (15 to 25 mg/week) of MTX for at least 4 weeks prior to Screening and willing to continue on their current regimen for the duration of the study. Stable doses of MTX as low as 10 mg/week are allowed when there is documented evidence of intolerance or safety issues at higher doses.

Exclusion Criteria:

* current therapy with any disease-modifying anti-rheumatic drugs (DMARD) other than MTX,
* current or previous RA treatment with a biologic DMARD, with the exception of biologic DMARDs administered in a single clinical study setting more than 6 months prior to Screening (12 months for rituximab or other B cell depleting agents), where the biologic DMARD was effective, and if discontinued, this should not be due to lack of efficacy,
* previous treatment at any time with a cytotoxic agent, other than MTX, before Screening.

Primary outcomes:
measure: Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Achieving an ACR20 Response at Week 24
timeFrame: Week 24
measure: Percentage of Participants Achieving an ACR50 Response at Weeks 1, 2, 4, 8, 12, and 24
timeFrame: Weeks 1, 2, 4, 8, 12, and 24
measure: Percentage of Participants Achieving an ACR70 Response at Weeks 1, 2, 4, 8, 12, and 24
timeFrame: Weeks 1, 2, 4, 8, 12, and 24
measure: ACR N% Improvement (ACR-N) Response at Weeks 1, 2, 4, 8, 12, and 24
timeFrame: Weeks 1, 2, 4, 8, 12, and 24
measure: Percentage of Participants With Disease Activity Score 28 Joints Corrected for CRP (DAS28 (CRP)) European League Against Rheumatism (EULAR) Response at Weeks 1, 2, 4, 8, 12, and 24
timeFrame: Weeks 1, 2, 4, 8, 12, and 24
measure: Percentage of Participants Achieving ACR/EULAR Remission at Weeks 2, 4, 8, 12, and 24
timeFrame: Weeks 2, 4, 8, 12, and 24
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 1, 2, 4, 8, 12, and 24
timeFrame: Baseline and Weeks 1, 2, 4, 8, 12, and 24
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 1, 2, 4, 8, 12, and 24
timeFrame: Baseline and Weeks 1, 2, 4, 8, 12, and 24
measure: Change From Baseline in Quality of Life Using the Functional Assessment of Chronic Illness Therapy (FACIT) at Weeks 4, 12, and 24
timeFrame: Baseline and Weeks 4, 12, and 24
measure: Change From Baseline in Quality of Life Using the Short Form-36 (SF-36) Scores at Weeks 4, 12, and 24
timeFrame: Baseline and Weeks 4, 12, and 24
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Rheumatology Associates of North Alabama, PC
state: Alabama
city: Gilbert
country: United States
facility: Artho Care, Arthritis Care & Research P.C.
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis & Rheumatology Research PLLC
state: Arizona
city: Hemet
country: United States
facility: C.V. Mehta MD Medical Corporation
state: California
city: La Jolla
country: United States
facility: Center for Innovative TherapyDivision of Rheumatology, UCSD
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Victorville
country: United States
facility: Desert Valley Medical Center
state: California
city: West Hills
country: United States
facility: Infosphere Clinical Research, Inc.
state: California
city: Boca Raton
country: United States
facility: RASF Clinical Research Center
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Venice
country: United States
facility: Lovelace Scientific Resources
state: Florida
city: Gainesville
country: United States
facility: Arthritis Center of North GA
state: Georgia
city: Meridian
country: United States
facility: Idaho Arthritis Center
state: Idaho
city: Springfield
country: United States
facility: The Arthritis Center
state: Illinois
city: Wichita
country: United States
facility: Professional Research Network of Kansas
state: Kansas
city: Frederick
country: United States
facility: Arthritis Treatment Center
state: Maryland
city: Hagerstown
country: United States
facility: Klein and Associates MD
state: Maryland
city: Lansing
country: United States
facility: Private practice
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Greenville
country: United States
facility: Physicians East
state: North Carolina
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center Clinical Research
state: Pennsylvania
city: Austin
country: United States
facility: Austin Rheumatology Research PA
state: Texas
city: Dallas
country: United States
facility: Arthritis Centers of Texas
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions Inc
state: Texas
city: Victoria
country: United States
facility: Crossroads Clinical Research, LLC
state: Texas
city: Seattle
country: United States
facility: Seattle Rheumatology Associates, PLLC
state: Washington
city: Clarksburg
country: United States
facility: Mountain State Clinical Research
state: West Virginia
city: Buenos Aires
country: Argentina
facility: Atencion Integral en Reumatologa
city: Buenos Aires
country: Argentina
facility: Rheumatology OMI
city: Cordoba
country: Argentina
facility: Instituto Reumatologico
city: Quilmes
country: Argentina
facility: Instituto Medico CER
city: San Fernando
country: Argentina
facility: Instituto de Asistencia Reumatologia Integral
city: Tucuman
country: Argentina
facility: Centro Médico Privado de Reumatología
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Daw Park
country: Australia
facility: Repatriation General Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Wien
country: Austria
facility: Medical University/ AKH Vienna/ Dep.of Rheumatology 6J
city: Brussels
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Brussels
country: Belgium
facility: Hospital Brugmann
city: Hasselt
country: Belgium
facility: Rheuma Instituut
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Liege
country: Belgium
facility: CHU de Liège
city: Plovdiv
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment - Kaspela" LTD
city: Ruse
country: Bulgaria
facility: MHAT Ruse AD
city: Sofia
country: Bulgaria
facility: Clinic of Rheumatology MHAT
city: Sofia
country: Bulgaria
facility: Diagnostic Consultative Center "Sveta Anna" LTD
city: Sofia
country: Bulgaria
facility: National Transport Hospital "Tsar Boris" III
city: Sofia
country: Bulgaria
facility: Rheumatology Clinic
city: Concepcion
country: Chile
facility: Hospital Regional "Guillermo Grant Benavente"
city: Santiago
country: Chile
facility: Instituto Terapias Oncologicas Providencia
city: Santiago
country: Chile
facility: Prosalud
city: Santiago
country: Chile
facility: Someal SA
city: Temuco
country: Chile
facility: Centro de Investigacion Clínica del Sur Freire
city: Temuco
country: Chile
facility: Private Office
city: Barranquilla
country: Colombia
facility: Centro Integral de Reumatologia de Caribe
city: Barranquilla
country: Colombia
facility: Fundación del caribe para la investigación medica Fundación BIOS
city: Bogota
country: Colombia
facility: Centro Integral de Reumatologia e Inmunologia SAS
city: Bogota
country: Colombia
facility: Cirei Sas
city: Bogota
country: Colombia
facility: Idearg S.A.S.
city: Bucaramanga
country: Colombia
facility: Medicity S.A.S.
city: Cali
country: Colombia
facility: Clinica de Arthritis Temprana S.A.S.
city: Cundinamarca
country: Colombia
facility: Preventive Care SAS
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
city: Brno
country: Czechia
facility: Revmatologie S.R.O
city: Kladno
country: Czechia
facility: Ambulance Revmatologie a Interniho Lekarstvi
city: Praha-Nusle
country: Czechia
facility: Revmatologicka ambulance
city: Uherske Hradiste
country: Czechia
facility: Medical Plus, s.r.o.
city: Zlin
country: Czechia
facility: PV-Medical
city: Strasbourg
country: France
facility: Hopitaux universitaires de Strasbourg
city: Berlin
country: Germany
facility: Charite Mitte, Rheumatologie Neue Therapien
city: Berlin
country: Germany
facility: Schlossparkklinik - Akad. Lehrkrankenhaus Charite
city: Frankfurt
country: Germany
facility: Klinikum Goethe-Universität
city: Hamburg
country: Germany
facility: Schwerpunktpraxis fuer Rheumatologie
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Guatemala City
country: Guatemala
facility: Centro Medico
city: Guatemala City
country: Guatemala
facility: Clinica de Especialidades Medicas
city: Guatemala City
country: Guatemala
facility: Clinica Medica Especializada en Reumatologia
city: Guatemala City
country: Guatemala
facility: Clinica Medica
city: Guatemala City
country: Guatemala
facility: Reuma S.A.
city: Guatemala
country: Guatemala
facility: Reuma-Centro
city: Balatonfured
country: Hungary
facility: DRC
city: Budapest
country: Hungary
facility: Budai Irgalmasrendi Korhaz
city: Budapest
country: Hungary
facility: Qualiclinic Ltd
city: Budapest
country: Hungary
facility: Revita Clinic
city: Eger
country: Hungary
facility: Markhot Ferenc Korhaz
city: Gyula
country: Hungary
facility: Bekes Megyei Pandy Kalman Korhaz, Reumatologiai Osztaly
city: Veszprem
country: Hungary
facility: Csolnoky Ferenc County Hospital
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Adazi
country: Latvia
facility: M&M Centre Ltd.
city: Daugavplis
country: Latvia
facility: Meda D
city: Liepaja
country: Latvia
facility: L. Atikes doktorats
city: Riga
country: Latvia
facility: "Bruninieku" polyclinic
city: Riga
country: Latvia
facility: Arija's Ancane's Family Doctor
city: Guadalajara
country: Mexico
facility: Centro de Estudios de Investigacion Basica y Clinica, SC
city: Mexico
country: Mexico
facility: Arké Estudios Clínicos
city: Mexico
country: Mexico
facility: Clinstile, S.A. de C.V.
city: Mexico
country: Mexico
facility: Hospital General de México
city: Monterrey
country: Mexico
facility: Accelerium Clinical Research
city: Monterrey
country: Mexico
facility: Hospital Universitario José E. González
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institutul de Cardiologie
city: Auckland
country: New Zealand
facility: North Shore hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Timaru
country: New Zealand
facility: Timaru Rheumatology Studies
city: Bialystok
country: Poland
facility: NZOZ Osteo-Medic s.c.
city: Bytom
country: Poland
facility: Silesiana Centrum Medyczne
city: Katowice
country: Poland
facility: Medica Pro Familia Sp. z o.o. S.K.A.
city: Krakow
country: Poland
facility: Centrum Medyczne Plejady
city: Krakow
country: Poland
facility: Nowomed
city: Krakow
country: Poland
facility: Nzoz "Dobry Lekarz"
city: Skierniewice
country: Poland
facility: NZOZ Przychodnia Lekarska "Eskulap"
city: Sroda Wielkopolska
country: Poland
facility: NS ZOZ Medicus Bonus
city: Starachowice
country: Poland
facility: Powiatowy Zakrad Opieki Zdrowotnej w Starachowicach
city: Torun
country: Poland
facility: NZOZ Nasz Lekarz
city: Warsaw
country: Poland
facility: AMED Medical Center
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny we Wroclawiu
city: Moscow
country: Russian Federation
facility: I.M. Sechenov First Moscow State Medical University
city: Moscow
country: Russian Federation
facility: Research Institute of Rheumatology RAMS
city: Moscow
country: Russian Federation
facility: State University of Medicine and Dentistry
city: Nizhniy Novgorod
country: Russian Federation
facility: City Clinical Hospital 5
city: Ryazan
country: Russian Federation
facility: Ryazan State Medical University
city: St Petersburg
country: Russian Federation
facility: City Hospital # 26
city: Vladimir
country: Russian Federation
facility: Vladimir Reg Clin Hosp
city: Cordoba
country: Spain
facility: Hospital Reina Sofa
city: Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Mostoles
country: Spain
facility: Hospital Universitario de Mostoles
city: Sabadell
country: Spain
facility: Consorci Sanitari Parc Tauli
city: Sevilla
country: Spain
facility: Hospital Infanta Luisa
city: Donetsk
country: Ukraine
facility: City Hospital #5
city: Donetsk
country: Ukraine
facility: V. Gusak Institute of Urgent and Recovery Surgery
city: Kharkiv
country: Ukraine
facility: City Hospital #13
city: Kharkiv
country: Ukraine
facility: City Hospital #8
city: Kharkiv
country: Ukraine
facility: Government Institution
city: Kiev
country: Ukraine
facility: Central Outpatient Hospital of Deanyanskyy Distric
city: Kyiv
country: Ukraine
facility: Central regional polyclinic of Pechersk District
city: Lutsk
country: Ukraine
facility: Municipal Institution Lutsk City Clinical Hospital
Study officials:
affiliation: Galapagos NV
name: Galapagos Study Director
role: STUDY_DIRECTOR
References:
citation: Combe B, Besuyen R, Gomez-Centeno A, Matsubara T, Sancho Jimenez JJ, Yin Z, Buch MH. Geographic Analysis of the Safety and Efficacy of Filgotinib in Rheumatoid Arthritis. Rheumatol Ther. 2023 Feb;10(1):35-51. doi: 10.1007/s40744-022-00494-1. Epub 2022 Oct 7.
citation: Tarrant JM, Galien R, Li W, Goyal L, Pan Y, Hawtin R, Zhang W, Van der Aa A, Taylor PC. Filgotinib, a JAK1 Inhibitor, Modulates Disease-Related Biomarkers in Rheumatoid Arthritis: Results from Two Randomized, Controlled Phase 2b Trials. Rheumatol Ther. 2020 Mar;7(1):173-190. doi: 10.1007/s40744-019-00192-5. Epub 2020 Jan 7.
citation: Westhovens R, Taylor PC, Alten R, Pavlova D, Enriquez-Sosa F, Mazur M, Greenwald M, Van der Aa A, Vanhoutte F, Tasset C, Harrison P. Filgotinib (GLPG0634/GS-6034), an oral JAK1 selective inhibitor, is effective in combination with methotrexate (MTX) in patients with active rheumatoid arthritis and insufficient response to MTX: results from a randomised, dose-finding study (DARWIN 1). Ann Rheum Dis. 2017 Jun;76(6):998-1008. doi: 10.1136/annrheumdis-2016-210104. Epub 2016 Dec 19.