A Phase 3b/4 Randomized, Double-Blind, Double Dummy, Active Comparator-Controlled Study, Comparing the Efficacy and Safety of Upadacitinib Versus Adalimumab in Subjects With Moderate to Severe Rheumatoid Arthritis on a Stable Background of MTX and Who Had an Inadequate Response or Intolerance to a Single TNF Inhibitor (SELECT- SWITCH)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 487
- 试验地点
- 225
- 主要终点
- Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) <= 3.2
研究概览
简要总结
Rheumatoid Arthritis (RA) is a chronic inflammatory disease causing pain, stiffness, swelling and loss of joint function. This study will assess how safe and effective upadacitinib is in treating RA when compared to adalimumab in adult participants with inadequate response or intolerance to one TNF-inhibitor who are on a stable dose of methotrexate (MTX). Adverse events and change in disease activity will be assessed.
Upadacitinib is an approved drug for the treatment of RA. This study is double-blinded means that neither the participants nor the study doctors will know who will be given upadacitinib and who will be given adalimumab. Study doctors put the participants in 1 of the 2 groups, called treatment arms randomly, to receive either upadacitinib or adalimumab. There is 1 in 2 chance that participants will receive adalimumab. Each group consists of 2 periods. Approximately 480 participants diagnosed with RA will be enrolled in approximately 250 sites across the world.
Participants will receive the oral upadacitinib once daily and matching adalimumab placebo every other week, or the subcutaneous adalimumab every other week and matching upadacitinib placebo once daily during Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1 and will be followed for 30 days and 70 days.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 四盲 (受试者、医护人员、研究者、结局评估者)
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 Rheumatoid Arthritis (RA) for >= 3 months based on the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria for RA.
- Treated for >= 3 consecutive months prior to screening with 1 tumor necrosis factor inhibitor (TNFi) (only 1 of originator or biosimilar certolizumab pegol, etanercept, golimumab or infliximab) for RA, but continue to exhibit active RA, or had to discontinue due to intolerability or toxicity, irrespective of treatment duration. Up to 15% of participants who were intolerant to 1 TNFi will be allowed to enroll. Prior administration of different biosimilar versions for the same originator TNFi or switching between originator and biosimilar version of the same originator TNFi are acceptable. Cycling between biosimilars of different originator TNF inhibitors is not acceptable.
- On oral or parenteral methotrexate (MTX) therapy >= 3 consecutive months and on a stable prescription of 15 to 25 mg/week (or >= 10 mg/week in participants intolerant of MTX at doses >= 15 mg/week) for >= 4 weeks prior to the first dose of study drug. In addition, all participants should take a dietary supplement of folic acid or folinic acid throughout the study participation.
- For a Chinese, Japanese, Korean, or Taiwanese participant, a stable dose of MTX >= 7.5 mg/week is acceptable.
- Additional local requirements for MTX may apply.
- Meets both of the following disease activity criteria:
- >= 6 swollen joint (based on 66 joint counts) and >= 6 tender joints (based on 68 joint counts) at screening and baseline;
- High-sensitivity C-reactive protein (hsCRP) >= 3 mg/L (central lab, upper limit of normal [ULN] 2.87 mg/L) at screening.
排除标准
- History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than Rheumatoid Arthritis (RA).
- Prior exposure to any janus kinase (JAK) inhibitor.
- Prior exposure to adalimumab (original or biosimilar) or to any approved or investigational TNF inhibitor other than infliximab, etanercept, certolizumab pegol and golimumab.
- Prior exposure to an approved or investigational non-TNFi biologic disease modifying anti-rheumatic drug (bDMARD) or targeted synthetic disease modifying antirheumatic drug (tsDMARD).
研究组 & 干预措施
Upadacitinib+ Adalimumab matching Placebo
Participants will receive upadacitinib once a day along with matching placebo for adalimumab at eow (every other week) in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.
干预措施: Upadacitinib (Drug)
Adalimumab + Upadacitinib matching Placebo
Participants will receive adalimumab at eow (every other week) along with matching placebo for upadacitinib once a day in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.
干预措施: Adalimumab (Drug)
Upadacitinib+ Adalimumab matching Placebo
Participants will receive upadacitinib once a day along with matching placebo for adalimumab at eow (every other week) in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.
干预措施: Adalimumab Matching Placebo (Drug)
Adalimumab + Upadacitinib matching Placebo
Participants will receive adalimumab at eow (every other week) along with matching placebo for upadacitinib once a day in Period 1. Eligible participants will continue to receive same study treatment in Period 2 as assigned in Period 1.
干预措施: Upadacitinib Matching Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) <= 3.2
时间窗: Week 12
The DAS28-CRP 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 (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.
Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) <= 3.2
时间窗: Week 12
The DAS28-CRP 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 (NRS), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.
Number of Participants with Adverse Events
时间窗: From first dose of study drug until 70 days following last dose of study drug (up to approximately 58 weeks)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not the event is considered causally related to the use of the product.
次要结局
- Percentage of Participants Achieving American College of Rheumatology 50 % (ACR50) Response(Week 12)
- Percentage of Participants Achieving Disease Activity Score 28 C-reactive Protein [DAS28-CRP]) < 2.6(Week 12)
- Change from Baseline in Disease Activity Score 28 C-reactive Protein [DAS28-CRP])(Week 12)
- Change from Baseline in Participants Assessment of Pain(Week 12)
- Change from Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Score(Week 12)
研究者
研究点 (225)
标识符
- NCT 编号
- NCT05814627
- 其他研究编号
- M23-700, 2022-502578-18-00
日期
- 首次提交
- (3年前)
- 首次发布
- (3年前)
- 主要完成日期
- (2个月前)
- 研究完成日期
- (2个月前)
- 最近核实
- (2个月前)
- 最近更新
- (上个月)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 否
AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.