Randomized, Double-blind, Placebo-controlled, Multicenter, Phase IIb Dose Finding Study of GLPG0634 Administered for 24 Weeks as Monotherapy to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (MTX) Alone
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Galapagos NV
- 入组人数
- 287
- 试验地点
- 82
- 主要终点
- Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
研究概览
简要总结
- 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.
详细描述
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Placebo
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.
干预措施: Placebo (Drug)
GLPG0634 50 mg QD
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.
干预措施: GLPG0634 (Drug)
GLPG0634 100 mg QD
Participants received GLPG0634 100 mg capsules, orally, QD during Weeks 1 to 24.
干预措施: GLPG0634 (Drug)
GLPG0634 200 mg QD
Participants received GLPG0634 200 mg capsules, orally, QD during Weeks 1 to 24.
干预措施: GLPG0634 (Drug)
结局指标
主要结局
Percentage of Participants Achieving an American College of Rheumatology (ACR) 20 Response at Week 12
时间窗: Week 12
The American College of Rheumatology (ACR) response is a measurement of improvement in multiple disease assessment criteria. The ACR20 response is defined as: 1) ≥ 20% improvement from baseline in SJC66, and 2) ≥ 20% improvement from baseline in tender TJC68, and 3) ≥ 20% improvement from baseline in at least 3 of the following 5 items: 1. Pain visual analog scale (VAS) (taken from the Health Assessment Questionnaire - Disability Index \[HAQ-DI\]), 2. Patient's Global Assessment of Disease Activity VAS, 3. Physician's Global Assessment of Disease Activity VAS, 4. Total HAQ-DI score, and 5. CRP. Non-responder imputation was used (ie, to impute a missing response, the participant was assumed to be a non-responder).
次要结局
- Percentage of Participants Achieving an ACR70 Response at Weeks 1, 2, 4, 8, 12, and 24(Weeks 1, 2, 4, 8, 12, and 24)
- Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 1, 2, 4, 8, 12, and 24(Baseline and Weeks 1, 2, 4, 8, 12, and 24)
- Percentage of Participants With Disease Activity Score 28 Joints Corrected for CRP (DAS28 (CRP)) European League Against Rheumatism (EULAR) Response at Weeks 1, 2, 4, 8, 12, and 24(Weeks 1, 2, 4, 8, 12, and 24)
- Percentage of Participants Achieving ACR/EULAR Remission at Weeks 2, 4, 8, 12, and 24(Weeks 4, 8, 12, and 24)
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 1, 2, 4, 8, 12, and 24(Baseline and Weeks 1, 2, 4, 8, 12, and 24)
- Percentage of Participants Achieving an ACR20 Response at Week 24(Week 24)
- Percentage of Participants Achieving an ACR50 Response at Weeks 1, 2, 4, 8, 12, and 24(Weeks 1, 2, 4, 8, 12, and 24)
- ACR N% Improvement (ACR-N) Response at Weeks 1, 2, 4, 8, 12, and 24(Weeks 1, 2, 4, 8, 12, and 24)
- Change From Baseline in Quality of Life Using the Short Form-36 (SF-36) Scores at Weeks 4, 12, and 24(Baseline and Weeks 4, 12, and 24)
- Change From Baseline in Quality of Life Using the Functional Assessment of Chronic Illness Therapy (FACIT) at Weeks 4, 12, and 24(Baseline and Weeks 4, 12, and 24)