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

NCT01894516 | Completed Phase 2 Results DMC

• 1 other identifier: GLPG0634-CL-204 (DARWIN2)
• Study Type: interventional
• Target: 287
• Locations: 18 countries
• Sites: 81

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.

Conditions

Rheumatoid Arthritis

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

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

GLPG0634 50 mg QD

EXPERIMENTAL

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.

Drug: GLPG0634

GLPG0634 100 mg QD

EXPERIMENTAL

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

Drug: GLPG0634

GLPG0634 200 mg QD

EXPERIMENTAL

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

Drug: GLPG0634

Interventions

GLPG0634 DRUG

GLPG0634 capsules.

GLPG0634 100 mg QD; GLPG0634 200 mg QD; GLPG0634 50 mg QD

Placebo DRUG

Placebo capsules.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Galapagos NV: lead

Study Sites (82)

Artho Care, Arthritis Care & Research P.C.

Gilbert, Arizona, United States

Location

Arizona Arthritis & Rheumatology Research PLLC

Mesa, Arizona, United States

Location

Arizona Arthritis Rheum Res

Phoenix, Arizona, United States

Location

Little Rock Diagnostic Clinic

Little Rock, Arkansas, United States

Location

C.V. Mehta MD Medical Corp.

Hemet, California, United States

Location

Center for Innovative Therapy Division of Rheumatology, UCSD

La Jolla, California, United States

Location

Desert Medical Advances

Palm Desert, California, United States

Location

Infosphere Clinical Research, Inc.

West Hills, California, United States

Location

Lovelace Scientific Resources

Venice, Florida, United States

Location

Arthritis Center of North GA

Gainesville, Georgia, United States

Location

The Arthritis Center

Springfield, Illinois, United States

Location

Klein and Associates MD

Hagerstown, Maryland, United States

Location

Private practice

Lansing, Michigan, United States

Location

Arthritis Center of Reno

Reno, Nevada, United States

Location

New Jersey Physicians, LLC

Clifton, New Jersey, United States

Location

Health research of Oklahoma

Oklahoma City, Oklahoma, United States

Location

Altoona Center Clin Research

Duncansville, Pennsylvania, United States

Location

Low Country Rheumatology, PA

Charleston, South Carolina, United States

Location

Arthritis Clinic

Jackson, Tennessee, United States

Location

Austin Rheumatology Research PA

Austin, Texas, United States

Location

Pioneer Research Solutions Inc

Houston, Texas, United States

Location

Centro de Investigaciones Medicas Lanus

Lanús, Argentina

Location

Instituto Centralizado de Asistencia e investigacion Clinica Integral

Rosario, Argentina

Location

Centro Médico Privado de Reumatología

San Miguel de Tucumán, Argentina

Location

Royal Prince Alfred Hospital

Camperdown, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Australia

Location

Rheumazentrum Favoriten

Vienna, Austria

Location

"Multiprofile Hospital for Active Treatment - Kaspela" LTD

Plovdiv, Bulgaria

Location

Clinic of Rheumatology MHAT

Sofia, Bulgaria

Location

Hospital Regional "Guillermo Grant Benavente"

Concepción, Chile

Location

Private Office

Temuco, Chile

Location

Fundación del Caribe para la Investigación Biomédica BIOS

Barranquilla, Colombia

Location

Centro Integral de Reumatologia SAS

Bogotá, Colombia

Location

Cirei Sas

Bogotá, Colombia

Location

Idearg S.A.S.

Bogotá, Colombia

Location

Medicity S.A.S.

Bucaramanga, Colombia

Location

Preventive Care Ltda

Chía, Colombia

Location

Schlossparkklinik - Akad. Lehrkrankenhaus Charite

Berlin, Germany

Location

Schwerpunktpraxis fuer Rheumatologie

Hamburg, Germany

Location

Clinica Médica Especializada en Medicina Interna

Guatemala City, Guatemala

Location

Reuma S.A.

Guatemala City, Guatemala

Location

Reuma-Centro

Guatemala City, Guatemala

Location

DRC

Balatonfüred, Hungary

Location

Qualiclinic Ltd

Budapest, Hungary

Location

Revita Clinic

Budapest, Hungary

Location

Csolnoky Ferenc County Hospital

Veszprém, Hungary

Location

L. Atikes doktorats

Liepāja, Latvia

Location

"Bruninieku" Polyclinic

Riga, Latvia

Location

Arké Estudios Clínicos S.A. de C.V.

México, Mexico

Location

Centro Medico Dalinde

México, Mexico

Location

Clinstile, S.A. de C.V.

México, Mexico

Location

Mexico Centre for Clinical Research

México, Mexico

Location

Hospital Universitario

Monterrey, Mexico

Location

Hospital de Especialidades

Oaxaca City, Mexico

Location

IMSP Institutul de Cardiologie

Chisinau, Moldova

Location

North Shore hospital

Auckland, New Zealand

Location

Timaru Rheumatology Studies

Timaru, New Zealand

Location

Silesiana Centrum Medyczne

Bytom, Poland

Location

Centrum Kliniczno

Elblag, Poland

Location

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

Katowice, Poland

Location

Nowomed

Krakow, Poland

Location

Nzoz "Dobry Lekarz"

Krakow, Poland

Location

NZOZ Przychodnia Lekarska "Eskulap"

Skierniewice, Poland

Location

NZOZ Medicus Bonus

Środa Wielkopolska, Poland

Location

AMED Medical Center

Warsaw, Poland

Location

Ars Rheumatica Sp. Z.o.o.

Warsaw, Poland

Location

Wojewodzki Szpital Specjalistyczny we Wroclawiu

Wroclaw, Poland

Location

Ianuli Med Consult SRL

Bucharest, Romania

Location

Sana Medical Center

Bucharest, Romania

Location

Spitalul Clinic Sfanta Maria

Bucharest, Romania

Location

Emergency County Hospital

Galati, Romania

Location

Orenburg State Medical Academy

Orenburg, Russia

Location

GUZ "Regional Clinical Hospital"

Saratov, Russia

Location

Vladimir Reg Clin Hosp

Vladimir, Russia

Location

Hospital General Elche

Elche, Spain

Location

Consorci Sanitari Parc Tauli

Sabadell, Spain

Location

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

Santiago de Compostela, Spain

Location

V. Gusak Institute of Urgent and Recovery Surgery

Donetsk, Ukraine

Location

City Hospital #8

Kharkiv, Ukraine

Location

Municipal Hospital

Kherson, Ukraine

Location

Central Outpatient Hospital of Deanyanskyy Distric

Kiev, Ukraine

Location

Regional Clinical Hospital

Vinnytsia, Ukraine

Location

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: 37747626 DERIVED

• 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.

  PMID: 36205910 DERIVED

• 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.

  PMID: 31912462 DERIVED

• 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.

  PMID: 27993828 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

GLPG0634

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: Galapagos N.V.

rd@glpg.com

+32 (0)15 342 900

Study Officials

• Galapagos Study Director

  Galapagos NV

  STUDY DIRECTOR

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: July 4, 2013
• First Posted: July 10, 2013
• Study Start: October 8, 2013
• Primary Completion: March 5, 2015
• Study Completion: May 29, 2015
• Last Updated: December 16, 2020
• Results First Posted: November 19, 2020

Record last verified: 2020-11

Locations

CO (6); GU (3); AR (3); HU (4); US (21); LA (2); AU (2); PL (10); RU (3); DE (2); CL (2); ME (6); UA (5); BU (2); ES (3); MO (1); RO (4); NZ (2)