Efficacy and Safety of Selective JAK 1 Inhibitor Filgotinib in Active Rheumatoid Arthritis Patients With Inadequate Response to Methotrexate: Comparative Study With Filgotinib and Tocilizumab Examined by Clinical Index as Well as Musculoskeletal Ultrasound Assessment
试验速览
- 阶段
- 3 期
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
研究概览
简要总结
The administration of Janus kinase (JAK) inhibitors as well as biological disease-modifying anti-rheumatic drugs has dramatically improved even the clinical outcomes in rheumatoid arthritis (RA) patients with inadequate response to methotrexate (MTX). The dysregulation of JAK-signal transducer and activator of transcription (STAT) pathways via overproduction of cytokines, such as interleukin-6 (IL-6) is involved in the pathogenesis of RA. Filgotinib is a selective JAK1 inhibitor to be approved for use in RA. Filgotinib is effective in suppressing disease activity and preventing the progression of joint destruction due to inhibition of the JAK-STAT pathway. IL-6 inhibitors such as tocilizumab also inhibit the JAK-STAT pathways due to inhibition of IL-6 signaling. We will evaluate whether the effectiveness and safety of filgotinib monotherapy is non-inferior to those of tocilizumab monotherapy in RA patients with inadequate response to MTX.
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
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must meet all of the following requirements to be considered for entry into the study:
- •≥20 years old
- •with the diagnosis of RA based on the ACR/EULAR 2010 RA Classification Criteria
- •with at least moderate disease activity defined as a DAS28-ESR ≥3.2 at the eligibility evaluation
- •treated with MTX for ≥8 weeks prior to the providing consent, including 4 weeks or more at the same doses of 8 to 16 mg per week (stable doses of <8 mg per week are allowed only in the presence of intolerance to higher doses)
- •ability and willingness to provide written informed consent and comply with the requirements of the study protocol
排除标准
- •The exclusion criteria are as follows:
- •concurrent use of a corticosteroid equivalent to >5 mg/day of prednisolone
- •applicable an item for the contraindication of filgotinib or tocilizumab
- •a previous use of a JAK inhibitor or IL-6 inhibitor
- •treatment with a corticosteroid and csDMARD and change of dose within 4 weeks prior to the providing consent
- •treatment with a biologic DMARD or a biosimilar DMARD (ie, infliximab, biosimilar of infliximab, adalimumab, biosimilar of adalimumab, golimumab, certolizumab pegol or abatacept) within 8 weeks prior to the providing consent
- •treatment with a TNF inhibitor (ie, etanercept or biosimilar of etanercept) within 4 weeks prior to the providing consent
- •use of a prohibited drug or therapy, other than the agents noted above, within 4 weeks prior to the providing consent
- •a complication causing musculoskeletal disorders other than RA (ie, ankylosing spondyloarthritis, reactive arthritis, psoriatic arthritis, crystal-induced arthritis, systemic lupus erythematosus, systemic scleroderma, inflammatory myopathy, or mixed connective tissue disease)
- •current pregnancy, breastfeeding, or noncompliant with a medically approved contraceptive regimen during and 12 months after the study period
- •inappropriateness for inclusion in this study as determined by the investigator
研究组 & 干预措施
Filgotinib monotherapy
The administration of filgotinib 200mg/day switched from MTX ± other csDMARDs throughout the study period.
干预措施: filgotinib 200mg/day (Drug)
Tocilizumab monotherapy
The administration of subcutaneous tocilizumab 162mg/biweekly switched from MTX ± other csDMARDs throughout the study period.
干预措施: subcutaneous tocilizumab 162mg/biweekly (Drug)
结局指标
主要结局
the proportion of patients who achieve an American College of Rheumatology (ACR) 50 response
时间窗: at week 12
次要结局
- changes in the simplified disease activity index (SDAI) value(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- changes in the serum levels of biomarkers(from baseline to weeks 2, 4, 12, 24, 36, and 52)
- the proportion of patients who achieve an ACR20 response(at weeks 2, 4, 8, 12, 24, 36 and 52)
- changes in the DAS28-CRP value(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- change in van der Heijde-modified total Sharp score (vdH-mTSS)(from baseline to weeks 24 and 52)
- changes in the morning stiffness duration(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- changes in the Disease Activity Score (DAS)28-ESR value(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- the proportion of patients who achieve an ACR50 response(at weeks 2, 4, 8, 24, 36 and 52)
- the proportion of patients who achieve an ACR70 response(at weeks 2, 4, 8, 12, 24, 36 and 52)
- changes in the clinical disease activity index (CDAI) value(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- changes in the total grayscale (GS) score(from baseline to weeks 4, 12, 24, 36, and 52)
- change in the EuroQol 5 Dimensions 5-Level (EQ-5D-5L) data(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- change in the Functional Assessment of Chronic Illness-Fatigue (FACIT-F) data(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- changes in the combined PD score(from baseline to weeks 4, 12, 24, 36, and 52)
- change in the Health Assessment Questionnaire-Disability Index (HAQ-DI) data(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
- changes in the total power Doppler (PD) score(from baseline to weeks 4, 12, 24, 36, and 52)
- changes in the morning stiffness activity(from baseline to weeks 2, 4, 8, 12, 24, 36, and 52)
研究者
Atsushi Kawakami
Professor
Nagasaki University