A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 Given With Methotrexate (MTX) in Subjects With Moderately to Severely Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response or Intolerance to Anti-TNF Biologic Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 276
- 主要终点
- Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
研究概览
简要总结
The primary objective is to compare the safety and efficacy of multiple doses of ABT-494 versus placebo in moderately to severely active RA subjects on stable background MTX therapy with inadequate response or intolerance to anti-TNF biologic therapy.
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
- •Diagnosed with rheumatoid arthritis (RA) based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria for ≥ 3 months.
- •Subjects must have been receiving oral or parenteral methotrexate (MTX) therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to initiating the study drug. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to initiating the study drug. Subjects should continue with their stable doses of MTX and folic acid throughout the study
- •Subjects have been treated with 1 or more anti-tumor necrosis factor (TNF) biologics (no maximum cap) for ≥ 3 months but continue to exhibit active RA, or had to discontinue due to intolerability or toxicity. In addition, subjects with prior exposure to non-anti-TNF biologic(s) (no maximum cap) (e.g., abatacept, rituximab, anakinra, or tocilizumab) are allowed.
- •Have active RA as defined by the following minimum disease activity criteria: ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline, ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline, high sensitivity C reactive protein (hs-CRP) > Upper Limit of Normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibody.
排除标准
- •Prior exposure to Janus Activated Kinase (JAK) inhibitor (e.g. tofacitinib, baricitinib)
- •Pregnant or breastfeeding female
- •Ongoing or active infection.
研究组 & 干预措施
Placebo BID
Placebo twice daily (BID) for 12 weeks.
干预措施: Placebo (Drug)
ABT-494 3 mg BID
ABT-494 3 mg twice daily (BID) for 12 weeks.
干预措施: ABT-494 (Drug)
ABT-494 6 mg BID
ABT-494 6 mg twice daily (BID) for 12 weeks.
干预措施: ABT-494 (Drug)
ABT-494 12 mg BID
ABT-494 12 mg twice daily (BID) for 12 weeks.
干预措施: ABT-494 (Drug)
ABT-494 18 mg BID
ABT-494 18 mg twice daily (BID) for 12 weeks.
干预措施: ABT-494 (Drug)
结局指标
主要结局
Number of Subjects Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
时间窗: Baseline (Week 0) and Week 12
Response defined as at least 20% reduction (improvement) compared with baseline in tender joint count (TJC68), swollen joint count (SJC66), and at least 3 of the 5 remaining ACR core set measures: patient's assessment of pain, patient's global assessment of disease activity (PtGA); physician's global assessment of disease activity (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), and high-sensitivity C-reactive protein (hs CRP). Last observation carried forward (LOCF) was used for missing data.
次要结局
- Number of Subjects Achieving American College of Rheumatology 50% (ACR50) Response at Week 12(Baseline (Week 0) and Week 12)
- Number of Subjects Achieving American College of Rheumatology 70% (ACR70) Response at Week 12(Baseline (Week 0) and Week 12)
- Number of Subjects Achieving CR Based on DAS28 at Week 12(Baseline (Week 0) and Week 12)
- Number of Subjects Achieving Low Disease Activity (LDA) Based on Disease Activity Score (DAS28) or Clinical Remission (CR) Based on (DAS28) at Week 12(Baseline (Week 0) and Week 12)