A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study With Upadacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 338
- 试验地点
- 43
- 主要终点
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
研究概览
简要总结
The study objectives of Period 1 of this study were to compare the efficacy, safety, and tolerability of upadacitinib versus placebo for the treatment of signs and symptoms of subjects from China and selected countries including Brazil and South Korea with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs.
The study objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in subjects with RA who have completed Period 1.
详细描述
This is a Phase 3 multicenter study that includes two periods. Period 1 is a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo for the treatment of signs and symptoms of participants with moderately to severely active RA who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs. Period 2 is an open label 52 week extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in participants with RA who have completed Period 1.
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
- •Diagnosis of RA for ≥ 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA.
- •Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug.
- •Participants must have failed (lack of efficacy) at least one of the following: methotrexate (MTX), sulfasalazine, or leflunomide.
- •The following csDMARDs are allowed: oral or parenteral MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.
- •A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.
- •Participant meets both of the following disease activity criteria:
- •≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits; and
- •High-sensitivity C-Reactive Protein (hsCRP) ≥ 3 mg/L at Screening
- •Participants with prior exposure to at most one biological disease-modifying anti-rheumatic drugs (bDMARD) may be enrolled (up to 20% of total number of subjects). Specifically, prior to enrollment:
- •Participants with limited exposure to bDMARD (< 3 months) OR
- •Participants who are responding to a bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).
- •Participants must have discontinued bDMARD therapy prior to the first dose of study drug.
排除标准
- •Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- •Participants who are considered inadequate responders (lack of efficacy) to bDMARD therapy as defined by the Investigator.
- •History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]. Current diagnosis of secondary Sjogren's Syndrome is permitted.
研究组 & 干预措施
Placebo / Upadacitinib 15 mg
Participants randomized to receive placebo once daily for 12 weeks in Period 1 followed by upadacitinib 15 mg once daily for up to 52 weeks in Period 2.
干预措施: Upadacitinib (Drug)
Placebo / Upadacitinib 15 mg
Participants randomized to receive placebo once daily for 12 weeks in Period 1 followed by upadacitinib 15 mg once daily for up to 52 weeks in Period 2.
干预措施: Placebo (Drug)
Upadacitinib 15 mg
Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1 and up to an additional 52 weeks in Period 2.
干预措施: Upadacitinib (Drug)
结局指标
主要结局
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
时间窗: Baseline and Week 12
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
次要结局
- Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12(Week 12)
- Percentage of Participants Achieving Low Disease Activity Based on Clinical Disease Activity Index (CDAI) at Week 12(Week 12)
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12(Baseline and Week 12)
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12(Baseline and Week 12)
- Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28 (CRP) at Week 12(Week 12)
- Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) at Week 12(Baseline and Week 12)
- Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12(Baseline and Week 12)
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12(Baseline and Week 12)
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1(Baseline and Week 1)