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

Galapagos

Status and phase: Completed; Phase 2

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Drug: GLPG0634

Study type: Interventional

Funder types: Industry

Identifiers

NCT01894516

GLPG0634-CL-204 (DARWIN2)

Details and patient eligibility

About

• 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.

Full description

• Treatment duration was 24 weeks in total.
• However, at Week 12, all participants on placebo and the participants on the 50 mg dose who had not achieved 20% improvement in swollen joint count (SJC66) and tender joint count (TJC68) were assigned (automatically via interactive web response system (IWRS)) to 100 mg once daily (QD) in a blinded fashion and continued treatment until Week 24.
• Participants in the other groups maintained their randomized treatment until Week 24.

Enrollment: 287 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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287 participants in 4 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

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