Clinical trial NCT01894516: Dose-finding Study of GLPG0634 as Monotherapy in Active Rheumatoid Arthritis (RA) Participants (DARWIN2)
Official title: Randomized, Double-blind, Placebo-controlled, Multicenter, Phase IIb Dose Finding Study of GLPG0634 Administered for 24 Weeks as Monotherapy to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (MTX) Alone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Galapagos NV
Sponsor class: INDUSTRY
First posted: 2013-07-10
Enrollment: 287
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 who had an inadequate response to methotrexate were evaluated for improvement of disease activity (efficacy) when taking GLPG0634 as monotherapy (3 different doses - 50 milligram (mg), 100 mg and 200 mg once daily) 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 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, all participants on placebo and the participants on the 50 mg dose who had not achieved 20% improvement in swollen joint count (SJC66) and tender joint count (TJC68) were assigned (automatically via interactive web response system (IWRS)) to 100 mg once daily (QD) in a blinded fashion and continued treatment until Week 24.
* Participants in the other groups maintained their randomized treatment until Week 24.

Eligibility criteria: Inclusion Criteria:

* male or female subjects who are ≥18 years of age on the day of signing informed consent,
* 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 shown an inadequate response in terms of either lack of efficacy or toxicity to MTX,
* have agreed to be washed out from MTX for a period of at least 4 weeks before or during the Screening period.

Exclusion Criteria:

* current therapy with any non-biological disease modifying anti-rheumatic drug (DMARD), with the exception of antimalarials, which must be at a stable dose for at least 12 weeks prior to Screening,
* current or previous RA treatment with a biologic DMARD, with the exception of biologic DMARDs: administered in a single clinical study setting, and; more than 6 months prior to Screening (12 months for rituximab or other B cell depleting agents), and; 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 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: Gilbert
country: United States
facility: Artho Care, Arthritis Care & Research P.C.
state: Arizona
city: Mesa
country: United States
facility: Arizona Arthritis & Rheumatology Research PLLC
state: Arizona
city: Phoenix
country: United States
facility: Arizona Arthritis Rheum Res
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Diagnostic Clinic
state: Arkansas
city: Hemet
country: United States
facility: C.V. Mehta MD Medical Corp.
state: California
city: La Jolla
country: United States
facility: Center for Innovative Therapy Division of Rheumatology, UCSD
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: West Hills
country: United States
facility: Infosphere Clinical Research, Inc.
state: California
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: Springfield
country: United States
facility: The Arthritis Center
state: Illinois
city: Hagerstown
country: United States
facility: Klein and Associates MD
state: Maryland
city: Lansing
country: United States
facility: Private practice
state: Michigan
city: Reno
country: United States
facility: Arthritis Center of Reno
state: Nevada
city: Clifton
country: United States
facility: New Jersey Physicians, LLC
state: New Jersey
city: Oklahoma City
country: United States
facility: Health research of Oklahoma
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center Clin Research
state: Pennsylvania
city: Charleston
country: United States
facility: Low Country Rheumatology, PA
state: South Carolina
city: Jackson
country: United States
facility: Arthritis Clinic
state: Tennessee
city: Austin
country: United States
facility: Austin Rheumatology Research PA
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions Inc
state: Texas
city: Lanus
country: Argentina
facility: Centro de Investigaciones Medicas Lanus
city: Rosario
country: Argentina
facility: Instituto Centralizado de Asistencia e investigacion Clinica Integral
city: Tucuman
country: Argentina
facility: Centro Médico Privado de Reumatología
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Wien
country: Austria
facility: Rheumazentrum Favoriten
city: Plovdiv
country: Bulgaria
facility: "Multiprofile Hospital for Active Treatment - Kaspela" LTD
city: Sofia
country: Bulgaria
facility: Clinic of Rheumatology MHAT
city: Concepcion
country: Chile
facility: Hospital Regional "Guillermo Grant Benavente"
city: Temuco
country: Chile
facility: Private Office
city: Barranquilla
country: Colombia
facility: Fundación del Caribe para la Investigación Biomédica BIOS
city: Bogota
country: Colombia
facility: Centro Integral de Reumatologia 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: Chia
country: Colombia
facility: Preventive Care Ltda
city: Berlin
country: Germany
facility: Schlossparkklinik - Akad. Lehrkrankenhaus Charite
city: Hamburg
country: Germany
facility: Schwerpunktpraxis fuer Rheumatologie
city: Guatemala City
country: Guatemala
facility: Clinica Médica Especializada en Medicina Interna
city: Guatemala City
country: Guatemala
facility: Reuma S.A.
city: Guatemala City
country: Guatemala
facility: Reuma-Centro
city: Balatonfüred
country: Hungary
facility: DRC
city: Budapest
country: Hungary
facility: Qualiclinic Ltd
city: Budapest
country: Hungary
facility: Revita Clinic
city: Veszprem
country: Hungary
facility: Csolnoky Ferenc County Hospital
city: Liepaja
country: Latvia
facility: L. Atikes doktorats
city: Riga
country: Latvia
facility: "Bruninieku" Polyclinic
city: Mexico
country: Mexico
facility: Arké Estudios Clínicos S.A. de C.V.
city: Mexico
country: Mexico
facility: Centro Medico Dalinde
city: Mexico
country: Mexico
facility: Clinstile, S.A. de C.V.
city: Mexico
country: Mexico
facility: Mexico Centre for Clinical Research
city: Monterrey
country: Mexico
facility: Hospital Universitario
city: Oaxaca
country: Mexico
facility: Hospital de Especialidades
city: Chisinau
country: Moldova, Republic of
facility: IMSP Institutul de Cardiologie
city: Auckland
country: New Zealand
facility: North Shore hospital
city: Timaru
country: New Zealand
facility: Timaru Rheumatology Studies
city: Bytom
country: Poland
facility: Silesiana Centrum Medyczne
city: Elblag
country: Poland
facility: Centrum Kliniczno
city: Katowice
country: Poland
facility: Medica Pro Familia Sp. z o.o. S.K.A.
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: NZOZ Medicus Bonus
city: Warsaw
country: Poland
facility: AMED Medical Center
city: Warszawa
country: Poland
facility: Ars Rheumatica Sp. Z.o.o.
city: Wroclaw
country: Poland
facility: Wojewodzki Szpital Specjalistyczny we Wroclawiu
city: Bucharest
country: Romania
facility: Ianuli Med Consult SRL
city: Bucuresti
country: Romania
facility: Sana Medical Center
city: Bucuresti
country: Romania
facility: Spitalul Clinic Sfanta Maria
city: Galati
country: Romania
facility: Emergency County Hospital
city: Orenburg
country: Russian Federation
facility: Orenburg State Medical Academy
city: Saratov
country: Russian Federation
facility: GUZ "Regional Clinical Hospital"
city: Vladimir
country: Russian Federation
facility: Vladimir Reg Clin Hosp
city: Elche
country: Spain
facility: Hospital General Elche
city: Sabadell
country: Spain
facility: Consorci Sanitari Parc Tauli
city: Santiago De Compostella
country: Spain
facility: CICEC S.L.P Hospital Ntra.Sra.de la Esperanza
city: Donetsk
country: Ukraine
facility: V. Gusak Institute of Urgent and Recovery Surgery
city: Kharkiv
country: Ukraine
facility: City Hospital #8
city: Kherson
country: Ukraine
facility: Municipal Hospital
city: Kiev
country: Ukraine
facility: Central Outpatient Hospital of Deanyanskyy Distric
city: Vinnytsya
country: Ukraine
facility: Regional 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: Kavanaugh A, Kremer J, Ponce L, Cseuz R, Reshetko OV, Stanislavchuk M, Greenwald M, Van der Aa A, Vanhoutte F, Tasset C, Harrison P. Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2). Ann Rheum Dis. 2017 Jun;76(6):1009-1019. doi: 10.1136/annrheumdis-2016-210105. Epub 2016 Dec 19.