Dose-finding Study of GLPG0634 as add-on to Methotrexate in Active Rheumatoid Arthritis Participants (DARWIN1)
DARWIN1
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
2 other identifiers
interventional
599
21 countries
138
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 rheumatoid-arthritis
Started Jul 2013
Typical duration for phase_2 rheumatoid-arthritis
138 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 26, 2013
CompletedFirst Posted
Study publicly available on registry
June 28, 2013
CompletedStudy Start
First participant enrolled
July 17, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 18, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
May 14, 2015
CompletedResults Posted
Study results publicly available
November 17, 2020
CompletedNovember 17, 2020
October 1, 2020
1.6 years
June 26, 2013
October 26, 2020
October 26, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
The American College of Rheumatology (ACR) response is a measurement of improvement in multiple disease assessment criteria. The ACR20 response is defined as: 1) ≥ 20% improvement from baseline in SJC66, and 2) ≥ 20% improvement from baseline in tender TJC68, and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain visual analog scale (VAS) (taken from the Health Assessment Questionnaire - Disability Index \[HAQ-DI\]), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used (ie, to impute a missing response, the participant was assumed to be a non-responder).
Week 12
Secondary Outcomes (10)
Percentage of Participants Achieving an ACR20 Response at Week 24
Week 24
Percentage of Participants Achieving an ACR50 Response at Weeks 1, 2, 4, 8, 12, and 24
Weeks 1, 2, 4, 8, 12, and 24
Percentage of Participants Achieving an ACR70 Response at Weeks 1, 2, 4, 8, 12, and 24
Weeks 1, 2, 4, 8, 12, and 24
ACR N% Improvement (ACR-N) Response at Weeks 1, 2, 4, 8, 12, and 24
Weeks 1, 2, 4, 8, 12, and 24
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
Weeks 1, 2, 4, 8, 12, and 24
- +5 more secondary outcomes
Study Arms (7)
Placebo
PLACEBO COMPARATORParticipants received GLPG0634 matching placebo capsules, orally, twice daily (BID) during Weeks 1 to 12. Participants who were responders (having at least 20 percent \[%\] improvement on TJC68 and SJC66) remained on placebo while nonresponders were re-randomized to GLPG0634 100 milligram (mg) once daily (QD) or 50 mg BID during Weeks 13 to 24.
GLPG0634 50 mg QD
EXPERIMENTALParticipants received GLPG0634 50 mg capsules, orally, QD during Weeks 1 to 12. Participants who were responders (having at least 20% improvement on TJC68 and SJC66) remained on 50 mg QD while nonresponders were re-randomized to 100 mg QD during Weeks 13 to 24.
GLPG0634 100 mg QD
EXPERIMENTALParticipants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24.
GLPG0634 200 mg QD
EXPERIMENTALParticipants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24.
GLPG0634 25 mg BID
EXPERIMENTALParticipants received GLPG0634 25 mg capsules, orally, BID during Weeks 1 to 12. Participants who were responders (having at least 20% improvement on TJC68 and SJC66) remained on 25 mg BID while nonresponders were re-randomized to 50 mg BID during Weeks 13 to 24.
GLPG0634 50 mg BID
EXPERIMENTALParticipants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24.
GLPG0634 100 mg BID
EXPERIMENTALParticipants received GLPG0634 100 mg capsules, orally, BID during Weeks 1 to 24.
Interventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Galapagos NVlead
Study Sites (142)
Rheumatology Associates of North Alabama, PC
Huntsville, Alabama, United States
Artho Care, Arthritis Care & Research P.C.
Gilbert, Arizona, United States
Arizona Arthritis & Rheumatology Research PLLC
Phoenix, Arizona, United States
C.V. Mehta MD Medical Corporation
Hemet, California, United States
Center for Innovative TherapyDivision of Rheumatology, UCSD
La Jolla, California, United States
Desert Medical Advances
Palm Desert, California, United States
Desert Valley Medical Center
Victorville, California, United States
Infosphere Clinical Research, Inc.
West Hills, California, United States
RASF Clinical Research Center
Boca Raton, Florida, United States
Millennium Research
Ormond Beach, Florida, United States
Lovelace Scientific Resources
Venice, Florida, United States
Arthritis Center of North GA
Gainesville, Georgia, United States
Idaho Arthritis Center
Meridian, Idaho, United States
The Arthritis Center
Springfield, Illinois, United States
Professional Research Network of Kansas
Wichita, Kansas, United States
Arthritis Treatment Center
Frederick, Maryland, United States
Klein and Associates MD
Hagerstown, Maryland, United States
Private practice
Lansing, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Physicians East
Greenville, North Carolina, United States
Health Research of Oklahoma
Oklahoma City, Oklahoma, United States
Altoona Center Clinical Research
Duncansville, Pennsylvania, United States
Austin Rheumatology Research PA
Austin, Texas, United States
Arthritis Centers of Texas
Dallas, Texas, United States
Pioneer Research Solutions Inc
Houston, Texas, United States
Crossroads Clinical Research, LLC
Victoria, Texas, United States
Seattle Rheumatology Associates, PLLC
Seattle, Washington, United States
Mountain State Clinical Research
Clarksburg, West Virginia, United States
Atencion Integral en Reumatologa
Buenos Aires, Argentina
Rheumatology OMI
Buenos Aires, Argentina
Instituto Reumatologico
Córdoba, Argentina
Instituto Medico CER
Quilmes, Argentina
Instituto de Asistencia Reumatologia Integral
San Fernando, Argentina
Centro Médico Privado de Reumatología
San Miguel de Tucumán, Argentina
Royal Prince Alfred Hospital
Camperdown, Australia
Monash Medical Centre
Clayton, Australia
Repatriation General Hospital
Daw Park, Australia
Princess Alexandra Hospital
Woolloongabba, Australia
Medical University/ AKH Vienna/ Dep.of Rheumatology 6J
Vienna, Austria
Cliniques Universitaires St-Luc
Brussels, Belgium
Hospital Brugmann
Brussels, Belgium
Rheuma Instituut
Hasselt, Belgium
AZ Groeninge
Kortrijk, Belgium
UZ Leuven
Leuven, Belgium
CHU de Liège
Liège, Belgium
"Multiprofile Hospital for Active Treatment - Kaspela" LTD
Plovdiv, Bulgaria
MHAT Ruse AD
Rousse, Bulgaria
Clinic of Rheumatology MHAT
Sofia, Bulgaria
Diagnostic Consultative Center "Sveta Anna" LTD
Sofia, Bulgaria
National Transport Hospital "Tsar Boris" III
Sofia, Bulgaria
Rheumatology Clinic
Sofia, Bulgaria
Hospital Regional "Guillermo Grant Benavente"
Concepción, Chile
Instituto Terapias Oncologicas Providencia
Santiago, Chile
Prosalud
Santiago, Chile
Someal SA
Santiago, Chile
Centro de Investigacion Clínica del Sur Freire
Temuco, Chile
Private Office
Temuco, Chile
Centro Integral de Reumatologia de Caribe
Barranquilla, Colombia
Fundación del caribe para la investigación medica Fundación BIOS
Barranquilla, Colombia
Centro Integral de Reumatologia e Inmunologia SAS
Bogotá, Colombia
Cirei Sas
Bogotá, Colombia
Idearg S.A.S.
Bogotá, Colombia
Medicity S.A.S.
Bucaramanga, Colombia
Clinica de Arthritis Temprana S.A.S.
Cali, Colombia
Preventive Care SAS
Cundinamarca, Colombia
Hospital Pablo Tobon Uribe
Medellín, Colombia
Revmatologie S.R.O
Brno, Czechia
Ambulance Revmatologie a Interniho Lekarstvi
Kladno, Czechia
Revmatologicka ambulance
Praha-Nusle, Czechia
Medical Plus, s.r.o.
Uherské Hradiště, Czechia
PV-Medical
Zlín, Czechia
Hopitaux universitaires de Strasbourg
Strasbourg, France
Charite Mitte, Rheumatologie Neue Therapien
Berlin, Germany
Schlossparkklinik - Akad. Lehrkrankenhaus Charite
Berlin, Germany
Klinikum Goethe-Universität
Frankfurt, Germany
Schwerpunktpraxis fuer Rheumatologie
Hamburg, Germany
Rheumazentrum Ruhrgebiet
Herne, Germany
Centro Medico
Guatemala City, Guatemala
Clinica de Especialidades Medicas
Guatemala City, Guatemala
Clinica Medica Especializada en Reumatologia
Guatemala City, Guatemala
Clinica Medica
Guatemala City, Guatemala
Reuma S.A.
Guatemala City, Guatemala
Reuma-Centro
Guatemala City, Guatemala
DRC
Balatonfüred, Hungary
Budai Irgalmasrendi Korhaz
Budapest, Hungary
Qualiclinic Ltd
Budapest, Hungary
Revita Clinic
Budapest, Hungary
Markhot Ferenc Korhaz
Eger, Hungary
Bekes Megyei Pandy Kalman Korhaz, Reumatologiai Osztaly
Gyula, Hungary
Csolnoky Ferenc County Hospital
Veszprém, Hungary
Carmel Medical Center
Haifa, Israel
Rambam Medical Center
Haifa, Israel
Sheba Medical Center
Ramat Gan, Israel
M&M Centre Ltd.
Ādaži, Latvia
Meda D
Daugavplis, Latvia
L. Atikes doktorats
Liepāja, Latvia
"Bruninieku" polyclinic
Riga, Latvia
Arija's Ancane's Family Doctor
Riga, Latvia
Centro de Estudios de Investigacion Basica y Clinica, SC
Guadalajara, Mexico
Arké Estudios Clínicos
México, Mexico
Clinstile, S.A. de C.V.
México, Mexico
Hospital General de México
México, Mexico
Accelerium Clinical Research
Monterrey, Mexico
Hospital Universitario José E. González
Monterrey, Mexico
Centro de Alta Especialidad en Reumatología e Investigación del Potosí, S.C.
San Luis Potosí City, Mexico
IMSP Institutul de Cardiologie
Chisinau, Moldova
North Shore hospital
Auckland, New Zealand
Waikato Hospital
Hamilton, New Zealand
Timaru Rheumatology Studies
Timaru, New Zealand
NZOZ Osteo-Medic s.c.
Bialystok, Poland
Silesiana Centrum Medyczne
Bytom, Poland
Medica Pro Familia Sp. z o.o. S.K.A.
Katowice, Poland
Centrum Medyczne Plejady
Krakow, Poland
Nowomed
Krakow, Poland
Nzoz "Dobry Lekarz"
Krakow, Poland
NZOZ Przychodnia Lekarska "Eskulap"
Skierniewice, Poland
Powiatowy Zakrad Opieki Zdrowotnej w Starachowicach
Starachowice, Poland
NS ZOZ Medicus Bonus
Środa Wielkopolska, Poland
NZOZ Nasz Lekarz
Torun, Poland
AMED Medical Center
Warsaw, Poland
Wojewodzki Szpital Specjalistyczny we Wroclawiu
Wroclaw, Poland
I.M. Sechenov First Moscow State Medical University
Moscow, Russia
Research Institute of Rheumatology RAMS
Moscow, Russia
State University of Medicine and Dentistry
Moscow, Russia
City Clinical Hospital 5
Nizhny Novgorod, Russia
Ryazan State Medical University
Ryazan, Russia
City Hospital # 26
Saint Petersburg, Russia
Vladimir Reg Clin Hosp
Vladimir, Russia
Complejo Hospitalario Universitario A Coruña
A Coruña, Spain
Hospital Reina Sofa
Córdoba, Spain
Hospital General Universitario de Elche
Elche, Spain
Hospital Universitario de Mostoles
Móstoles, Spain
Consorci Sanitari Parc Tauli
Sabadell, Spain
Hospital Infanta Luisa
Seville, Spain
City Hospital #5
Donetsk, Ukraine
V. Gusak Institute of Urgent and Recovery Surgery
Donetsk, Ukraine
City Hospital #13
Kharkiv, Ukraine
City Hospital #8
Kharkiv, Ukraine
Government Institution
Kharkiv, Ukraine
Central Outpatient Hospital of Deanyanskyy Distric
Kiev, Ukraine
Central regional polyclinic of Pechersk District
Kyiv, Ukraine
Municipal Institution Lutsk City Clinical Hospital
Lutsk, Ukraine
Related Publications (4)
Balsa A, Wassenberg S, Tanaka Y, Tournadre A, Orzechowski HD, Rajendran V, Lendl U, Stiers PJ, Watson C, Caporali R, Galloway J, Verschueren P. Effect of Filgotinib on Body Mass Index (BMI) and Effect of Baseline BMI on the Efficacy and Safety of Filgotinib in Rheumatoid Arthritis. Rheumatol Ther. 2023 Dec;10(6):1555-1574. doi: 10.1007/s40744-023-00599-1. Epub 2023 Sep 25.
PMID: 37747626DERIVEDCombe 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.
PMID: 36205910DERIVEDTarrant 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.
PMID: 31912462DERIVEDWesthovens 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.
PMID: 27993829DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Clinical Trial Information Desk
- Organization
- Galapagos N.V.
Study Officials
- STUDY DIRECTOR
Galapagos Study Director
Galapagos NV
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 26, 2013
First Posted
June 28, 2013
Study Start
July 17, 2013
Primary Completion
February 18, 2015
Study Completion
May 14, 2015
Last Updated
November 17, 2020
Results First Posted
November 17, 2020
Record last verified: 2020-10