A Randomized, Double-blind, Placebo- and Active-controlled, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Filgotinib Administered for 52 Weeks Alone and in Combination With Methotrexate (MTX) to Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are Naïve to MTX Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,252
- 主要终点
- Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20% Improvement (ACR20) Response at Week 24
研究概览
简要总结
The primary objective of this study is to evaluate the effects of filgotinib in combination with methotrexate (MTX) versus MTX alone in adults with active rheumatoid arthritis (RA).
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
- Double (Participant, Investigator)
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
- •Have a diagnosis of RA (2010 American College of Rheumatology [ACR]/European League Against Rheumatism [EULAR] criteria) and are ACR functional class I-III.
- •Have ≥ 6 swollen joints (from a swollen joint count based on 66 joints (SJC66)) and ≥ 6 tender joints (from a tender joint count based on 68 joints (TJC68)) at both screening and Day
- •Limited or no prior treatment with MTX
排除标准
- •Previous treatment with any janus kinase (JAK) inhibitor
- •Previous therapy for longer than 3 months with conventional synthetic disease modifying antirheumatic drugs (csDMARDs) other than MTX or hydroxychloroquine
- •Use of any licensed or investigational biologic disease-modifying antirheumatic drugs (DMARDs)
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
MTX Monotherapy
Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg + MTX up to 20 mg
干预措施: MTX (Drug)
MTX Monotherapy
Placebo to match filgotinib 200 mg + placebo to match filgotinib 100 mg + MTX up to 20 mg
干预措施: Placebo to match filgotinib (Drug)
Filgotinib 200 mg + MTX
Filgotinib 200 mg + placebo to match filgotinib 100 mg + MTX up to 20 mg
干预措施: Filgotinib (Drug)
Filgotinib 200 mg + MTX
Filgotinib 200 mg + placebo to match filgotinib 100 mg + MTX up to 20 mg
干预措施: Placebo to match filgotinib (Drug)
Filgotinib 200 mg + MTX
Filgotinib 200 mg + placebo to match filgotinib 100 mg + MTX up to 20 mg
干预措施: MTX (Drug)
Filgotinib 100 mg + MTX
Filgotinib 100 mg + placebo to match filgotinib 200 mg + MTX up to 20 mg
干预措施: Filgotinib (Drug)
Filgotinib 100 mg + MTX
Filgotinib 100 mg + placebo to match filgotinib 200 mg + MTX up to 20 mg
干预措施: Placebo to match filgotinib (Drug)
Filgotinib 100 mg + MTX
Filgotinib 100 mg + placebo to match filgotinib 200 mg + MTX up to 20 mg
干预措施: MTX (Drug)
Filgotinib 200 mg Monotherapy
Filgotinib 200 mg + placebo to match filgotinib 100 mg + placebo to match MTX
干预措施: Filgotinib (Drug)
Filgotinib 200 mg Monotherapy
Filgotinib 200 mg + placebo to match filgotinib 100 mg + placebo to match MTX
干预措施: Placebo to match filgotinib (Drug)
Filgotinib 200 mg Monotherapy
Filgotinib 200 mg + placebo to match filgotinib 100 mg + placebo to match MTX
干预措施: Placebo to match MTX (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved an American College of Rheumatology (ACR) 20% Improvement (ACR20) Response at Week 24
时间窗: Week 24
ACR20 response is achieved when the participant has: ≥ 20% improvement (reduction) from baseline in tender joint count based on 68 joints (TJC68), swollen joint count based on 66 joints (SJC66) and in at least 3 of the following 5 items: physician's global assessment of disease activity (PGA) and subject's global assessment of disease activity (SGA) assessed using visual analog scale (VAS) on a scale of 0-100 (0 and 100 indicating no disease activity and maximum disease activity); subject's pain assessment using VAS on a scale of 0-100 (0 and 100 indicating no pain and unbearable pain); health assessment questionnaire-disability index (HAQ-DI) score contains 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities and scored on a scale of 0-3 (0 and 3 indicating without difficulty and unable to do); high-sensitivity C-reactive protein (hsCRP). Participants with missing outcomes were set as non-responders.
次要结局
- Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24(Baseline; Week 24)
- Percentage of Participants Who Achieved Disease Activity Score for 28 Joint Count Using C-Reactive Protein [DAS28 (CRP)] < 2.6 at Week 24(Week 24)
- Change From Baseline in the Modified Total Sharp Score (mTSS) at Week 24(Baseline; Week 24)
- FACIT-Fatigue Score at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in 36-Item Short Form Survey (SF-36) Physical Component Summary (PCS) Score at Week 24(Baseline; Week 24)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 24(Baseline; Week 24)
- Change From Baseline in the mTSS at Week 52(Baseline; Week 52)
- Percentage of Participants Who Achieved ACR20 Response at Weeks 2, 4, 12, 36, and 52(Weeks 2, 4, 12, 36, and 52)
- Percentage of Participants Who Achieved ACR 50% Improvement (ACR50) at Weeks 2, 4, 12, 24, 36, and 52(Weeks 2, 4, 12, 24, 36, and 52)
- Percentage of Participants Who Achieved ACR 70% Improvement (ACR70) at Weeks 2, 4, 12, 24, 36, and 52(Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Individual ACR Component: HAQ-DI at Weeks 2, 4, 12, 36, and 52(Baseline; Weeks 2, 4, 12, 36, and 52)
- Change From Baseline in Individual ACR Component: Tender Joint Count Based on 68 Joints (TJC68) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Individual ACR Component: Swollen Joint Count Based on 66 Joints (SJC66) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Individual ACR Component: Subject's Global Assessment of Disease Activity (SGA) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Individual ACR Component: Physician's Global Assessment of Disease Activity (PGA) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Individual ACR Component: Subject's Pain Assessment at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Individual ACR Component: High-Sensitivity C-Reactive Protein (hsCRP) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Percentage of Participants Who Achieved an Improvement (Decrease) in the HAQ-DI Score ≥ 0.22 at Weeks 2, 4, 12, 24, 36, and 52(Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Change From Baseline in DAS28 (CRP) at Weeks 2, 4, 12, 24, 36, and 52(Baseline; Weeks 2, 4, 12, 24, 36, and 52)
- Percentage of Participants Who Achieved DAS28 (CRP) ≤ 3.2 at Weeks 4, 12, 24, and 52(Weeks 4, 12, 24, and 52)
- Percentage of Participants Who Achieved DAS28 (CRP) < 2.6 at Weeks 2, 4, 12, 36, and 52(Weeks 2, 4, 12, 36, and 52)
- WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- ACR N Percent Improvement (ACR-N) Response at Weeks 2, 4, 12, 24, 36, and 52(Weeks 2, 4, 12, 24, 36, and 52)
- Number of Participants With European League Against Rheumatism (EULAR) Response at Weeks 2, 4, 12, 24, 36, and 52(Weeks 2, 4, 12, 24, 36, and 52)
- Percentage of Participants With no Radiographic Progression From Baseline at Weeks 24, and 52(Baseline; Weeks 24, and 52)
- SF-36 PCS Score at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in SF-36 PCS Score at Weeks 4, 12, 36, and 52(Baseline; Weeks 4, 12, 36, and 52)
- SF-36 Mental Component Summary (MCS) Score at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in SF-36 MCS Score at Weeks 4, 12, 24, 36, and 52(Baseline; Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in FACIT-Fatigue Score at Weeks 4, 12, 36, and 52(Baseline; Weeks 4, 12, 36, and 52)
- Number of Participants by European Quality of Life 5 Dimensions (EQ-5D) Health Profile Categories at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- EQ-5D Current Health VAS at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in EQ-5D Current Health VAS at Weeks 4, 12, 24, 36, and 52(Baseline; Weeks 4, 12, 24, 36, and 52)
- Work Productivity and Activity Impairment-Rheumatoid Arthritis (WPAI-RA): Mean Percentage of Work Time Missed (Absenteeism) at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 4, 12, 24, 36, and 52(Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in WPAI-RA: Mean Percentage of Work Time Missed (Absenteeism) at Weeks 4, 12, 24, 36, and 52(Baseline; Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in WPAI-RA: Mean Percentage of Impairment While Working Due to RA (Presenteeism) at Weeks 4, 12, 24, 36, and 52(Baseline; Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in WPAI-RA: Mean Percentage of Overall Work Productivity Impairment Due to RA at Weeks 4, 12, 24, 36, and 52(Baseline; Weeks 4, 12, 24, 36, and 52)
- Change From Baseline in WPAI-RA: Mean Percentage of Activity Impairment Due to RA at Weeks 4, 12, 24, 36, and 52(Baseline; Weeks 4, 12, 24, 36, and 52)