A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo on Stable Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) in Subjects With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response or Intolerance to Biologic DMARDs (bDMARDs)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 499
- 试验地点
- 188
- 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 objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and symptoms of participants with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and had an inadequate response to or intolerance to at least 1 bDMARD.
The study objective of Period 2 (Week 24 to Week 260) is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg QD and 30 mg QD in participants with RA who completed Period 1.
详细描述
This study includes a 35-day screening period; a 24-week randomized, double-blind, parallel-group, placebo controlled treatment period (Period 1); a 236-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit).
Period 1 consists of a 12-week double-blind, placebo-controlled treatment phase plus a 12-week double-blind phase where all participants were to receive upadacitinib; at Week 12 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.
Participants who meet eligibility criteria will be randomized in a 2:2:1:1 ratio to one of four treatment groups:
- Group 1: Upadacitinib 30 mg QD (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter)
- Group 2: Upadacitinib 15 mg QD (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter)
- Group 3: Placebo (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter)
- Group 4: Placebo (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter)
Participants will continue stable dose of csDMARD therapy for the first 24 weeks of the study.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of rheumatoid arthritis (RA) for≥ 3 months.
- •Treated for ≥ 3 months with ≥ 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration prior to the first dose of study drug.
- •Participant has been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.
- •Meets both of the following criteria:
- •≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
- •hsCRP ≥ 3mg/L at Screening Visit.
排除标准
- •Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- •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
Upadacitinib 15 mg
Period 1: Participants receive upadacitinib 15 mg once daily for 24 weeks.
Period 2: Participants will continue on upadacitinib 15 mg once daily from Week 24 to Week 260.
干预措施: Upadacitinib (Drug)
Upadacitinib 30 mg
Period 1: Participants receive upadacitinib 30 mg once daily for 24 weeks.
Period 2: Participants continue on upadacitinib 30 mg once daily until implementation of Protocol Amendment 4, then participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Upadacitinib (Drug)
Placebo / Upadacitnib 15 mg
Period 1: Participants receive placebo once daily for 12 weeks followed by upadacitinib 15 mg once daily for 12 weeks.
Period 2: Participants will continue on upadacitinib 15 mg once daily from Week 24 to Week 260.
干预措施: Placebo (Drug)
Placebo / Upadacitnib 15 mg
Period 1: Participants receive placebo once daily for 12 weeks followed by upadacitinib 15 mg once daily for 12 weeks.
Period 2: Participants will continue on upadacitinib 15 mg once daily from Week 24 to Week 260.
干预措施: Upadacitinib (Drug)
Placebo / Upadacitnib 30 mg
Period 1: Participants receive placebo once daily for 12 weeks followed by upadacitinib 30 mg once daily for 12 weeks.
Period 2: Participants continue on upadacitinib 30 mg once daily until implementation of Protocol Amendment 4, then participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Placebo (Drug)
Placebo / Upadacitnib 30 mg
Period 1: Participants receive placebo once daily for 12 weeks followed by upadacitinib 30 mg once daily for 12 weeks.
Period 2: Participants continue on upadacitinib 30 mg once daily until implementation of Protocol Amendment 4, then participants begin to receive upadacitinib 15 mg once daily up to Week 260.
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
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at 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).
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
时间窗: Week 12
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at Week 12. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity.
次要结局
- Change From Baseline in in Disease Activity Score 28 (CRP) 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)
- 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 50% (ACR50) Response 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)