Dose-finding Study of GLPG0634 as Monotherapy in Active Rheumatoid Arthritis (RA) Participants (DARWIN2)

NCT ID: NCT01894516

Last Updated: 2020-12-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

287 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-08

Study Completion Date

2015-05-29

Brief Summary

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* 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

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* 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.

Conditions

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Rheumatoid Arthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Participants received GLPG0634 matching placebo capsules, orally, once daily (QD) during Weeks 1 to 12 and GLPG0634 100 milligram (mg) QD during Weeks 13 to 24.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo capsules.

GLPG0634 50 mg QD

Participants 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.

Group Type EXPERIMENTAL

GLPG0634

Intervention Type DRUG

GLPG0634 capsules.

GLPG0634 100 mg QD

Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24.

Group Type EXPERIMENTAL

GLPG0634

Intervention Type DRUG

GLPG0634 capsules.

GLPG0634 200 mg QD

Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24.

Group Type EXPERIMENTAL

GLPG0634

Intervention Type DRUG

GLPG0634 capsules.

Interventions

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GLPG0634

GLPG0634 capsules.

Intervention Type DRUG

Placebo

Placebo capsules.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Galapagos NV

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Galapagos Study Director

Role: STUDY_DIRECTOR

Galapagos NV

Locations

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Artho Care, Arthritis Care & Research P.C.

Gilbert, Arizona, United States

Site Status

Arizona Arthritis & Rheumatology Research PLLC

Mesa, Arizona, United States

Site Status

Arizona Arthritis Rheum Res

Phoenix, Arizona, United States

Site Status

Little Rock Diagnostic Clinic

Little Rock, Arkansas, United States

Site Status

C.V. Mehta MD Medical Corp.

Hemet, California, United States

Site Status

Center for Innovative Therapy Division of Rheumatology, UCSD

La Jolla, California, United States

Site Status

Desert Medical Advances

Palm Desert, California, United States

Site Status

Infosphere Clinical Research, Inc.

West Hills, California, United States

Site Status

Lovelace Scientific Resources

Venice, Florida, United States

Site Status

Arthritis Center of North GA

Gainesville, Georgia, United States

Site Status

The Arthritis Center

Springfield, Illinois, United States

Site Status

Klein and Associates MD

Hagerstown, Maryland, United States

Site Status

Private practice

Lansing, Michigan, United States

Site Status

Arthritis Center of Reno

Reno, Nevada, United States

Site Status

New Jersey Physicians, LLC

Clifton, New Jersey, United States

Site Status

Health research of Oklahoma

Oklahoma City, Oklahoma, United States

Site Status

Altoona Center Clin Research

Duncansville, Pennsylvania, United States

Site Status

Low Country Rheumatology, PA

Charleston, South Carolina, United States

Site Status

Arthritis Clinic

Jackson, Tennessee, United States

Site Status

Austin Rheumatology Research PA

Austin, Texas, United States

Site Status

Pioneer Research Solutions Inc

Houston, Texas, United States

Site Status

Centro de Investigaciones Medicas Lanus

Lanús, , Argentina

Site Status

Instituto Centralizado de Asistencia e investigacion Clinica Integral

Rosario, , Argentina

Site Status

Centro Médico Privado de Reumatología

San Miguel de Tucumán, , Argentina

Site Status

Royal Prince Alfred Hospital

Camperdown, , Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, , Australia

Site Status

Rheumazentrum Favoriten

Vienna, , Austria

Site Status

"Multiprofile Hospital for Active Treatment - Kaspela" LTD

Plovdiv, , Bulgaria

Site Status

Clinic of Rheumatology MHAT

Sofia, , Bulgaria

Site Status

Hospital Regional "Guillermo Grant Benavente"

Concepción, , Chile

Site Status

Private Office

Temuco, , Chile

Site Status

Fundación del Caribe para la Investigación Biomédica BIOS

Barranquilla, , Colombia

Site Status

Centro Integral de Reumatologia SAS

Bogotá, , Colombia

Site Status

Cirei Sas

Bogotá, , Colombia

Site Status

Idearg S.A.S.

Bogotá, , Colombia

Site Status

Medicity S.A.S.

Bucaramanga, , Colombia

Site Status

Preventive Care Ltda

Chía, , Colombia

Site Status

Schlossparkklinik - Akad. Lehrkrankenhaus Charite

Berlin, , Germany

Site Status

Schwerpunktpraxis fuer Rheumatologie

Hamburg, , Germany

Site Status

Clinica Médica Especializada en Medicina Interna

Guatemala City, , Guatemala

Site Status

Reuma S.A.

Guatemala City, , Guatemala

Site Status

Reuma-Centro

Guatemala City, , Guatemala

Site Status

DRC

Balatonfüred, , Hungary

Site Status

Qualiclinic Ltd

Budapest, , Hungary

Site Status

Revita Clinic

Budapest, , Hungary

Site Status

Csolnoky Ferenc County Hospital

Veszprém, , Hungary

Site Status

L. Atikes doktorats

Liepāja, , Latvia

Site Status

"Bruninieku" Polyclinic

Riga, , Latvia

Site Status

Arké Estudios Clínicos S.A. de C.V.

México, , Mexico

Site Status

Centro Medico Dalinde

México, , Mexico

Site Status

Clinstile, S.A. de C.V.

México, , Mexico

Site Status

Mexico Centre for Clinical Research

México, , Mexico

Site Status

Hospital Universitario

Monterrey, , Mexico

Site Status

Hospital de Especialidades

Oaxaca City, , Mexico

Site Status

IMSP Institutul de Cardiologie

Chisinau, , Moldova

Site Status

North Shore hospital

Auckland, , New Zealand

Site Status

Timaru Rheumatology Studies

Timaru, , New Zealand

Site Status

Silesiana Centrum Medyczne

Bytom, , Poland

Site Status

Centrum Kliniczno

Elblag, , Poland

Site Status

Medica Pro Familia Sp. z o.o. S.K.A.

Katowice, , Poland

Site Status

Nowomed

Krakow, , Poland

Site Status

Nzoz "Dobry Lekarz"

Krakow, , Poland

Site Status

NZOZ Przychodnia Lekarska "Eskulap"

Skierniewice, , Poland

Site Status

NZOZ Medicus Bonus

Środa Wielkopolska, , Poland

Site Status

AMED Medical Center

Warsaw, , Poland

Site Status

Ars Rheumatica Sp. Z.o.o.

Warsaw, , Poland

Site Status

Wojewodzki Szpital Specjalistyczny we Wroclawiu

Wroclaw, , Poland

Site Status

Ianuli Med Consult SRL

Bucharest, , Romania

Site Status

Sana Medical Center

Bucharest, , Romania

Site Status

Spitalul Clinic Sfanta Maria

Bucharest, , Romania

Site Status

Emergency County Hospital

Galati, , Romania

Site Status

Orenburg State Medical Academy

Orenburg, , Russia

Site Status

GUZ "Regional Clinical Hospital"

Saratov, , Russia

Site Status

Vladimir Reg Clin Hosp

Vladimir, , Russia

Site Status

Hospital General Elche

Elche, , Spain

Site Status

Consorci Sanitari Parc Tauli

Sabadell, , Spain

Site Status

CICEC S.L.P Hospital Ntra.Sra.de la Esperanza

Santiago de Compostela, , Spain

Site Status

V. Gusak Institute of Urgent and Recovery Surgery

Donetsk, , Ukraine

Site Status

City Hospital #8

Kharkiv, , Ukraine

Site Status

Municipal Hospital

Kherson, , Ukraine

Site Status

Central Outpatient Hospital of Deanyanskyy Distric

Kiev, , Ukraine

Site Status

Regional Clinical Hospital

Vinnytsia, , Ukraine

Site Status

Countries

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United States Argentina Australia Austria Bulgaria Chile Colombia Germany Guatemala Hungary Latvia Mexico Moldova New Zealand Poland Romania Russia Spain Ukraine

References

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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.

Reference Type DERIVED
PMID: 37747626 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36205910 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31912462 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27993828 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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GLPG0634-CL-204 (DARWIN2)

Identifier Type: -

Identifier Source: org_study_id