A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) Monotherapy to Methotrexate (MTX) in Adults With Moderately to Severely Active Rheumatoid Arthritis With Inadequate Response to MTX
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 648
- 试验地点
- 153
- 主要终点
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14
研究概览
简要总结
The study objective of Period 1 of this study is to compare the safety and efficacy (signs and symptoms) of upadacitinib 30 mg once daily (QD) alone and upadacitinib 15 mg QD alone versus continuing MTX alone adults with moderately to severely active rheumatoid arthritis (RA) with an inadequate response to MTX.
The study objective of Period 2 is to evaluate the long term safety, tolerability, and efficacy of upadacitinib 30 mg QD and 15 mg QD in adults with RA who had completed Period 1.
详细描述
The study includes a 35-day screening period; a 14-week randomized, double-blind, parallel-group, controlled treatment period (Period 1); a 246-week blinded extension period (Period 2); and a 30-day follow-up visit.
Participants who met eligibility criteria were to be randomized in a 2:2:1:1 ratio to one of four treatment groups:
- Group 1: upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2)
- Group 2: upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2)
- Group 3: MTX (Period 1) → upadacitinib 30 mg QD (Period 2)
- Group 4: MTX (Period 1) → upadacitinib 15 mg QD (Period 2)
Starting with implementation of Protocol Amendment 5, all participants in the extension period will receive open-label upadacitinib 15 mg QD, including those currently on upadacitinib 30 mg QD.
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 RA for >= 3 months.
- •Subjects must have been on oral or parenteral MTX therapy >= 3 months and on a stable dose for >= 4 weeks prior to first dose of study drug.
- •Must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) (other than MTX) >= 4 weeks prior to first dose of study drug.
- •Meets the following minimum 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.
排除标准
- •Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
- •Prior exposure to any biological disease-modifying anti-rheumatic drugs (bDMARDs).
- •Current diagnosis of inflammatory joint disease other than RA. Current diagnosis of secondary Sjogren's Syndrome is permitted.
研究组 & 干预措施
Upadacitinib 30 mg
Period 1: Participants receive upadacitnib 30 mg once daily and placebo to methotrexate once weekly for 14 weeks.
Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Upadacitinib (Drug)
Upadacitinib 30 mg
Period 1: Participants receive upadacitnib 30 mg once daily and placebo to methotrexate once weekly for 14 weeks.
Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Placebo Methotrexate (Drug)
Upadacitinib 15 mg
Period 1: Participants receive upadacitnib 15 mg once daily and placebo to methotrexate once weekly for 14 weeks.
Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Upadacitinib (Drug)
Upadacitinib 15 mg
Period 1: Participants receive upadacitnib 15 mg once daily and placebo to methotrexate once weekly for 14 weeks.
Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Placebo Methotrexate (Drug)
Methotrexate / Upadacitinib 30 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib once daily for 14 weeks.
Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Methotrexate (Drug)
Methotrexate / Upadacitinib 30 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib once daily for 14 weeks.
Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Upadacitinib (Drug)
Methotrexate / Upadacitinib 30 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib once daily for 14 weeks.
Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Placebo Upadacitinib (Drug)
Methotrexate / Upadacitinib 30 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib once daily for 14 weeks.
Period 2: Participants receive upadacitinib 30 mg once daily until implementation of Protocol Amendment 5 when participants begin to receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Placebo Methotrexate (Drug)
Methotrexate / Upadacitinib 15 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib for 14 weeks.
Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Methotrexate (Drug)
Methotrexate / Upadacitinib 15 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib for 14 weeks.
Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Upadacitinib (Drug)
Methotrexate / Upadacitinib 15 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib for 14 weeks.
Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Placebo Upadacitinib (Drug)
Methotrexate / Upadacitinib 15 mg
Period 1: Participants receive methotrexate once weekly and placebo to upadacitinib for 14 weeks.
Period 2: Participants receive upadacitinib 15 mg once daily up to Week 260.
干预措施: Placebo Methotrexate (Drug)
结局指标
主要结局
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 14
时间窗: Baseline and week 14
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 14. 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 14
时间窗: Week 14
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 14. 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 14(Baseline to week 14)
- Change From Baseline in Heath Assessment Questionnaire and Disability Index (HAQ-DI) at Week 14(Baseline to week 14)
- Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 14(Baseline to week 14)
- Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 14(Week 14)
- Change From Baseline in Duration of Morning Stiffness at Week 14(Baseline to week 14)
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 14(Baseline and week 14)
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 14(Baseline and week 14)