Efficacy and Safety of Iguratimod Combined With Tofacitinib in the Treatment of csDMARD-IR Patients With Active Moderate-to-severe Rheumatoid Arthritis： a Prospective, Randomized, Controlled, Multicenter Study
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 138
- 主要终点
- The percentage of patients who achieve clinical remission at week 24 using European League Against Rheumatism (EULAR) response criteria DAS28
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of Iguratimod combined with Tofacitinib in the treatment of csDMARD-IR patients with active moderate-to-severe rheumatoid arthritis
详细描述
After being informed about the study and potential risks, all patients giving written informed consent will undergo a 1-week screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a double-blind manner (participant and investigator) in a 1:1 ratio to Iguratimod (25mg, twice daily) combined with Tofacitinib (5mg, twice daily) or placebo (25mg, twice daily) combined with Tofacitinib (5mg, twice daily).
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who meet the following inclusion criteria will be eligible to participate in the study:
- •Male or female aged 18-65 years old;
- •Weight not less than 40kg;
- •Since the diagnosis of RA, the course of disease was ≥6 months;
- •Patients who meet RA standards in 1987 and 2010 ;
- •RA patients with moderate to high disease activity (DAS28 > 3.2) at the time of screening;
- •Active RA (≥6 joints swelling [66 joints count]; ≥Tenderness of 6 joints [68 joint counts]; ESR>28 mm/h or C-reactive protein (CRP) >1.0 mg/dL);
- •Poor response or intolerance to at least one DMARD, including csDMARDs, bDMARDs, but not tsDMARDs;
- •Previous use of any JAK inhibitor was discontinued for six months before enrollment;
- •For patients who have used DMARDs, the washout criteria must be met;
- •Written informed consent;
排除标准
- •Patients who meet any of the following criteria will be excluded from the study:
- •Pregnant or lactating women;
- •Platelet count < 10^9/L, or white blood cell < 3*10^9/L, or absolute neutrophil count < 1.2*10^9/L, or Hemoglobin < 9 g/dL or hematocrit <30%;
- •According to Cockcroft-Gault, the glomerular filtration rate was ≤40 ml/min.
- •ALT>1.5×ULN, AST>1.5×ULN, Cr>135umol/L;
- •Subjects with serious cardiovascular, renal, hematologic or endocrine diseases;
- •A history of autoimmune rheumatic diseases other than Sjogren's syndrome;
- •Subjects with uncontrolled infection;
- •Subjects receiving live vaccines within 6 weeks prior to study entry;
- •history of alcohol or drug abuse and abstinence for less than 6 months prior to the first use of the study drug;
- •Subjects participating in other clinical study within 3 months prior to study entry;
- •Have a history of malignant tumor;
- •History of recurrent herpes zoster, diffuse herpes zoster;
- •People who are allergic to any of the study drugs;
- •Other conditions in which the investigator deemed the patient inappropriate for trial entry;
研究组 & 干预措施
Double-Blind Placebo
Placebo (25mg twice daily) combined with Tofacitinib (5mg twice daily) for 24 weeks (6 months)
干预措施: Iguratimod combined with Tofacitinib; (Drug)
Double-Blind Iguratimod
Iguratimod (25mg twice daily) combined with Tofacitinib (5mg twice daily) for 24 weeks (6 months)
干预措施: Iguratimod combined with Tofacitinib; (Drug)
结局指标
主要结局
The percentage of patients who achieve clinical remission at week 24 using European League Against Rheumatism (EULAR) response criteria DAS28
时间窗: week 24
The proportion of patients with DAS28-CRP\<2.6 at the end of 24 weeks was compared between the two groups. The DAS28 is a composite score derived from 4 of these measures，that is the count of tender joint count（TJC, 0-28）and swollen joint count（SJC, 0-28）, measure C reactive protein (CRP, mg/L) and to make a patient assessment of disease activity.
次要结局
- Percentage of American College of Rheumatology [ACR] 20 Criteria Responders at the end of 24 weeks was compared between the two groups.(week 24)
- Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at the end of 24 weeks was compared between the two groups.(week 24)
- Percentage of American College of Rheumatology [ACR] 70 Criteria Responders at the end of 24 weeks was compared between the two groups.(week 24)
- The change of DAS28 score between the two groups at the end of 24 weeks was compared with the baseline value (week 0)(up to week 24)
- The change of Clinical Disease Activity Index (CDAI) score between the two groups at the end of 24 weeks was compared with the baseline value (week 0)(up to week 24)
- The proportion of patients with SDAI≤3.3 at the end of 24 weeks was compared between the two groups.(week 24)
- The change of Simplified Disease Activity Index (SDAI) score between the two groups at the end of 24 weeks was compared with the baseline value (week 0)(up to week 24)
- The percentage of patients who achieve clinical remission at week 12 using European League Against Rheumatism (EULAR) response criteria DAS28(week 12)
- The proportion of patients with CDAI≤2.8 at the end of 24 weeks was compared between the two groups.(week 24)
- The changes of ACPA, RF, serum immunoglobulin (IgG, IgA, IgM) levels between the two groups at the end of 24 weeks were compared with the baseline values (week 0).(up to week 24)
- The drug retention rate was compared between the two groups at the end of 12 and 24 weeks.(week 12 and 24)
- The proportion of patients with minimal clinically important difference (MCID) of 0.22 on the Health Assessment Questionnaire Disability Index (HAQ-DI) was compared between the two groups at the end of 24 weeks.(week 24)