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

Galapagos

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: GLPG0634; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT01888874

GLPG0634-CL-203 (DARWIN1)

2012-003635-31 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 599 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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599 participants in 7 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

GLPG0634 50 mg QD

Experimental group

Description:

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.

Treatment:

Drug: GLPG0634

GLPG0634 100 mg QD

Experimental group

Description:

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

Treatment:

Drug: GLPG0634

GLPG0634 200 mg QD

Experimental group

Description:

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

Treatment:

Drug: GLPG0634

GLPG0634 25 mg BID

Experimental group

Description:

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.

Treatment:

Drug: GLPG0634

GLPG0634 50 mg BID

Experimental group

Description:

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

Treatment:

Drug: GLPG0634

GLPG0634 100 mg BID

Experimental group

Description:

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

Treatment:

Drug: GLPG0634