Randomized, Double-blind, Placebo-controlled, Multicenter, Phase IIb Dose Finding Study of GLPG0634 Administered for 24 Weeks in Combination With Methotrexate to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate Alone

Galapagos NV142 sites in 6 countries599 target enrollmentStarted: July 17, 2013Last updated: November 17, 2020

Conditions

Interventions

Drugs

Trial Snapshot

Phase: Phase 2
Status: Completed
Sponsor: Galapagos NV
Enrollment: 599
Locations: 142
Primary Endpoint: Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12

Study Overview Study Design Eligibility Criteria Arms & Interventions Outcomes Investigators Sites Records & Identifiers Similar Trials

Study Overview

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.

Study Design

Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel
Primary Purpose: Treatment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Eligibility Criteria

Ages: 18 Years to — (Adult, Older Adult)
Sex: All
Accepts Healthy Volunteers: No

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.

Arms & Interventions

Placebo

Placebo Comparator

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.

Intervention: Placebo (Drug)

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.