A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects with Moderately to Severely Active Rheumatoid Arthritis Who are on a Stable Background of Methotrexate (MTX) and Who Have an Inadequate Response to MTX (MTX-IR)
概览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 489
- 试验地点
- 67
- 主要终点
- The primary endpoint is the proportion of subjects achieving ACR20 response at Week 12 or the proportion of subjects achieving clinical remission (CR) based on DAS28 (CRP) at Week 12
概览
简要总结
Period 1 • To compare the efficacy of upadacitinib QD versus placebo, and versus adalimumab (ADA) for the treatment of signs and symptoms of rheumatoid arthritis (RA) in subjects with moderately to severely active RA who are on a on a stable background of methotrexate (MTX) and who have an inadequate response to MTX (MTX-IR). • To compare the efficacy of upadacitinib QD versus placebo for the prevention of structural progression in RA subjects with moderately to severely active RA who are on a on a stable background of MTX and who have an inadequate response to MTX (MTX-IR). • To compare the safety and tolerability of upadacitinib QD versus placebo, and versus ADA in subjects with moderately to severely active RA subjects who are on a stable background of MTX and who have an inadequate response to MTX (MTX-IR).
Period 2 • To evaluate the long-term safety, tolerability, and efficacy of upadacitinib in subjects with RA who have completed Period 1.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Period 2
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Adult male or female, at least 18 years old.
- •Diagnosis of RA for ≥ 3 months
- •Subjects must have been on oral or parenteral MTX therapy ≥ 3 months and on a stable prescription of 15 to 25 mg/week (or ≥ 10 mg/week in subjects intolerant of MTX at doses ≥ 12.5 mg/week) for ≥ 4 weeks prior to the first dose of study drug. In addition, all subjects should take a dietary supplement of folic acid or folinic acid throughout the study participation.
- •Subjects meeting both: ≥ 6 swollen joints and ≥ 6 tender joints at screening and baseline, and hsCRP ≥ 5 mg/L at screening
- •At least one of the following at Screening: ≥ 3 bone erosions on x-ray OR ≥ 1 bone erosion and a positive rheumatoid factor OR ≥ 1 bone erosion and a positive anti-cyclic citrullinated peptide autoantibodies.
- •Subjects with prior exposure to at most one bDMARD (except ADA) may be enrolled (up to 20% of total study population)
- •Except for MTX, subject must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
排除标准
- •Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- •Subjects who have had any exposure to adalimumab or subjects who have been treated with other bDMARD therapy for ≥ 3 months who are considered inadequate responders (lack of efficacy) to bDMARD therapy as determined by the Investigator.
- •History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.
研究组 & 干预措施
-
Participants receiving -
干预措施: - (Drug)
结局指标
主要结局
The primary endpoint is the proportion of subjects achieving ACR20 response at Week 12 or the proportion of subjects achieving clinical remission (CR) based on DAS28 (CRP) at Week 12
The primary endpoint is the proportion of subjects achieving ACR20 response at Week 12 or the proportion of subjects achieving clinical remission (CR) based on DAS28 (CRP) at Week 12
次要结局
- Change from baseline in Disease Activity Score (DAS)28 (C-reactive protein [CRP]) at Week 12
- Change from baseline in mTSS at Week 26
- Change from baseline in HAQ-DI at Week 12
- ACR50 response rate at Week 12 (non-inferiority of upadacitinib versus ADA)
- Change from baseline in Short Form 36 (SF-36) Physical Component Score (PCS) at Week 12
- Proportion of subjects achieving low disease activity (LDA) based on DAS28 [CRP] ≤ 3.2 at Week 12
- Proportion of subjects achieving clinical remission (CR) based on DAS28 (CRP) at Week 12
- Proportion of subjects achieving LDA based on Clinical Disease Activity Index (CDAI) at Week 12
- Change from baseline in morning stiffness at Week 12
- Change from baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) at Week 12
- ACR50 response rate at Week 12 (superiority of upadacitinib vs. ADA)
- Change from baseline in Patient's Assessment of Pain at Week 12 (superiority of upadacitinib vs. ADA)
- Change from baseline in HAQ-DI at Week 12 (superiority of upadacitinib vs. ADA)
- Other key secondary endpoints (upadacitinib versus placebo): 1) ACR50 response rate at Week 12, 2) ACR70 response rate at Week 12, 3) Proportion of subjects with no radiographic progression (defined as change from baseline mTSS ≤ 0) at Week 26
研究者
Global Clinical Trials Helpdesk
Scientific
Abbvie Deutschland GmbH & Co. KG