Dose-finding Study of GLPG0634 as add-on to Methotrexate in Active Rheumatoid Arthritis Participants (DARWIN1)

NCT ID: NCT01888874

Last Updated: 2020-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 599 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-17
• Study Completion Date: 2015-05-14

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.

Conditions

Rheumatoid Arthritis

Keywords

Methotrexate inadequate responders

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants 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.

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.

GLPG0634 25 mg BID

Participants 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.

Group Type: EXPERIMENTAL

GLPG0634

Intervention Type: DRUG

GLPG0634 capsules.

GLPG0634 50 mg BID

Participants received GLPG0634 50 mg capsules, orally, BID during Weeks 1 to 24.

Group Type: EXPERIMENTAL

GLPG0634

Intervention Type: DRUG

GLPG0634 capsules.

GLPG0634 100 mg BID

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

Group Type: EXPERIMENTAL

GLPG0634

Intervention Type: DRUG

GLPG0634 capsules.

Interventions

GLPG0634

GLPG0634 capsules.

Intervention Type: DRUG

Placebo

Placebo capsules.

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Galapagos NV

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Galapagos Study Director

Role: STUDY_DIRECTOR

Galapagos NV

Locations

Charite Mitte, Rheumatologie Neue Therapien

Berlin, , Germany

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

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

Countries

Peru; Puerto Rico; United States; Argentina; Australia; Austria; Belgium; Bulgaria; Chile; Colombia; Czechia; France; Germany; Guatemala; Hungary; Israel; Latvia; Mexico; Moldova; New Zealand; Poland; Russia; Spain; Ukraine

References

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)

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.

Reference Type: DERIVED

PMID: 27993829 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2012-003635-31

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GLPG0634-CL-203 (DARWIN1)

Identifier Type: -

Identifier Source: org_study_id