Safety and Preliminary Efficacy of GLPG0634 in Methotrexate-refractory Active Rheumatoid Arthritis Patients

• Thirty six patients suffering from active rheumatoid arthritis despite continued treatment with methotrexate will be evaluated for improvement of disease activity when taking GLPG0634 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: GLPG0634

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chisinau, Moldova, Republic of, MD-2025
    • Innophar MO S.R.L.

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 six months or longer and at a stable dose of 7.5 to 25 mg/week (extremes included) for at least four 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 four weeks prior to screening;
• If taking non-steroidal anti-inflammatory drugs (NSAIDs), these must be at a stable dose for at least two 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 (12 consecutive months without menses);
• 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 four 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;
• Receipt of an intra-articular or parenteral corticosteroid injection within four weeks prior to screening;
• Known hypersensitivity to study drug ingredients or a significant allergic reaction to any drug as determined by the Investigator, such as anaphylaxis, requiring hospitalization;
• Positive serology for human immunodeficiency virus (HIV)1 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;
• Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo oral capsules	Drug: GLPG0634
Experimental: GLPG0634 100 mg bid oral capsules	Drug: GLPG0634
Experimental: GLPG0634 200 mg qd oral capsules	Drug: GLPG0634

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 preliminarily evaluate the efficacy of GLPG0634 compared to placebo in terms of the proportion of subjects achieving an ACR20 response at Week 4	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description
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]
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)
The plasma levels of GLPG0634 as a measure of PK and the levels of immune- and inflammation-related parameters in blood as a measure of PD	To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of GLPG0634 in subjects with rheumatoid arthritis (RA)

Collaborators and Investigators

• Sponsor: Galapagos NV

Publications and helpful links

General Publications

• Namour F, Diderichsen PM, Cox E, Vayssiere B, Van der Aa A, Tasset C, Van't Klooster G. Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection. Clin Pharmacokinet. 2015 Aug;54(8):859-74. doi: 10.1007/s40262-015-0240-z.
• 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: June 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: June 27, 2011
• First Submitted That Met QC Criteria: June 28, 2011
• First Posted (Estimate): June 29, 2011

Study Record Updates

• Last Update Posted (Estimate): August 15, 2012
• Last Update Submitted That Met QC Criteria: August 14, 2012
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: methotrexate-refractory
• 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-201