Dose-ranging Study With GLPG0634 in Methotrexate-refractory Active Rheumatoid Arthritis Patients

Randomized, Double-blind, Placebo-controlled, Multicenter, Phase II Study to Compare Four Dose Regimens of GLPG0634 Versus Placebo, in Combination With Methotrexate, Administered for 4 Weeks in the Treatment of Subjects With Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Alone

• Ninety patients suffering from active rheumatoid arthritis despite continued treatment with methotrexate will be evaluated for improvement of disease activity when taking GLPG0634 (4 different doses will be evaluated) or matching placebo for 4 weeks.
• During the course of the study, patients will also be examined for any side effects that may occur, and the amount of GLPG0634 present in the blood as well as the effects of GLPG0634 on disease- and mechanism of action-related parameters in the blood will be determined.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Placebo; Drug: GLPG0634

• Study Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • Budai Irgalamsrendi Korhaz, II. Reumatologia Osztaly
  • Budapest, Hungary
    • Orszagos Reumatologiai es Fizioterapias Intezet, I. Reumatologia Osztaly
  • Eger, Hungary
    • Markhot Ferenc Korhaz, Reumatologiai Osztaly
  • Kistarcsa, Hungary
    • Pest Megyei Flor Ferenc Korhaz, Reumatologiai es Fizioterapias Osztaly
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • IMSP Institutel de Cardiologie
• Russian Federation
  • Moscow, Russian Federation
    • State Healthcare Institution of city Moscow 'City Clinical Hospital #7'
  • Ryazan, Russian Federation
    • State Healthcare Institution 'Ryazan Regional Cardiology Dispensary'
  • Saint-Petersburg, Russian Federation
    • Saint-Petersburg State Healthcare Institution 'City Hospital #26'
  • Saint-Petersburg, Russian Federation
    • Saint-Petersburg State Healthcare Institution 'City Mariinskiy Hospital'
  • Yaroslavl, Russian Federation
    • Municipal Clinical Healthcare Institution 'Medical-Sanitary Unit of Novoyaroslavskiy Oil Refinery'
• Ukraine
  • Chernivtsi, Ukraine
    • Chernivtsi Regional Clinical Hospital
  • Donetsk, Ukraine
    • State Institution 'Institute of Urgent and Recovery Surgery n.a. V.K. Gusaka' of AMS of Ukraine
  • Kharkiv, Ukraine
    • Communal Institution of Healthcare
  • Kharkiv, Ukraine
    • Institution of Therapy of AMS of Ukraine
  • Kharkiv, Ukraine
    • State Institution 'Institute of Microbiology and Immunology of AMS of Ukraine'
  • Kiev, Ukraine
    • State Institution 'Republican Clinical Hospital of MoH of Ukraine'
  • Lutsk, Ukraine
    • Lutsk City Clinical Hospital
  • Vinnytsa, Ukraine
    • Vinnytsa Regional Clinical Hospital
  • Zaporizhzhia, Ukraine
    • Zaporizhzhia Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have active RA as shown by five or more swollen joints (from the 66-joint count), five or more tender joints (from 68-joint count), and a serum CRP ≥1.0 mg/dL;
• Have received methotrexate for 12 weeks or longer and at a stable dose of 7.5 to 25 mg/week for at least 4 weeks prior to screening and willing to continue on this regimen for the duration of the study;
• If taking oral steroids, these should be at a dose ≤10 mg/day of prednisone or prednisone equivalent and stable for at least 4 weeks prior to screening;
• If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least 2 weeks prior to screening;
• Female subjects must have a negative pregnancy test unless they are surgically sterile or have been post-menopausal for at least one year;
• Women of childbearing potential must use a medically acceptable means of birth control and agree to continue its use during the study and for at least 12 weeks after the last dose of study drug.
• Sexually active men must agree to use a medically acceptable form of contraception during the study and continue its use for at least 3 months after the last dose of study drug; and
• Able and willing to sign the informed consent prior to screening evaluations and agree to schedule of assessments.

Exclusion Criteria:

• Treatment with disease-modifying antirheumatic drugs (DMARDs), other than background methotrexate;
• Current or previous RA treatment with a biological agent, with the exception of biologics administered in a clinical study setting more than six months prior to screening (12 months for rituximab or other B cell depleting agents);
• Previous treatment at any time with a cytotoxic agent, other than methotrexate, before screening;
• Previous use of the study drug GLPG0634;
• Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks prior to screening;
• Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the Investigator;
• Positive serology for HIV1 or 2 or hepatitis B or C, or any history of hepatitis from any cause with the exception of hepatitis A;
• History of any inflammatory rheumatological disorders other than RA;
• History of tuberculosis (TB) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: capsule, 30mg GLPG0634 once a day; 3 capsules of 10 mg once a day	Drug: GLPG0634
Experimental: capsules, 75mg GLPG0634 once a day; 3 capsules of 25mg once a day	Drug: GLPG0634
Experimental: capsules, 150mg GLPG0634 once a day; 3 capsules of 50mg once a day	Drug: GLPG0634
Experimental: capsules, 300mg GLPG0634 once a day; 3 capsules of 100mg once a day	Drug: GLPG0634
Placebo Comparator: capsules, placebo once a day; 3 capsules placebo once a day	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients with an ACR20 score at Week 4 as a measure of efficacy	To preliminary evaluate the efficacy of GLPG0634 compared to placebo in terms of the proportion of subjects achieving an ACR20 response at Week 4	Week 4 (end of treatment visit)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of patients with ACR20/50/70 response, time to response and DAS28 score at every visit as a measure of efficacy	To evaluate the efficacy of GLPG0634 compared to placebo in terms of ACR response criteria at every visit (ACR20, ACR50, ACR70), time to response, and disease status (DAS28[C-reactive protein, CRP]	From Day -1 up to end of treatment visit (week 4)
The number of patients with adverse events, abnormal lab tests, vital signs and ECG as a measure of safety and tolerability	To evaluate the safety and tolerability of GLPG0634 in comparison with placebo in terms of adverse events (AEs), laboratory test abnormalities, vital signs and electrocardiogram (ECG)	From screening up to 10 days after last dose
The plasma levels of GLPG0634 as a measure of PK	To characterize the pharmacokinetics (PK) of GLPG0634 by measuring the amount of GLPG0634 in the plasma	Week 1, week 2 and week 4 visits
The plasma levels of GLPG0634 and MTX as a measure of PK	To explore the potential interaction of GLPG0634 on MTX by assessing steady state PK in an 8-hour sampling at Day -1 and at Week 2 or Week 4 visit in a subset of patients	Day -1 and Week 2 or 4 visit (8 hour-sampling)
The levels of immune- and inflammation-related parameters in plasma as a measure of PD	To characterize the pharmacodynamics (PD) of GLPG0634 by measuring the levels of immune- and inflammation-related parameters in plasma	Day -1, Week 1, week 2 and week 4 visits

Collaborators and Investigators

• Sponsor: Galapagos NV

Publications and helpful links

General Publications

• Vanhoutte F, Mazur M, Voloshyn O, Stanislavchuk M, Van der Aa A, Namour F, Galien R, Meuleners L, van 't Klooster G. Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Filgotinib, a Selective JAK-1 Inhibitor, After Short-Term Treatment of Rheumatoid Arthritis: Results of Two Randomized Phase IIa Trials. Arthritis Rheumatol. 2017 Oct;69(10):1949-1959. doi: 10.1002/art.40186. Epub 2017 Aug 31.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: August 14, 2012
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (Estimate): August 20, 2012

Study Record Updates

• Last Update Posted (Estimate): June 27, 2013
• Last Update Submitted That Met QC Criteria: June 26, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Methotrexate insufficient responders
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: GLPG0634-CL-202