A Multi-center, Prospective, Open-label, Randomized Study to Explore Efficacy and Safety of Baricitinib in Refractory Intestinal Behçet's Syndrome Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 56
- 试验地点
- 2
- 主要终点
- Proportion of patients with marked improvement (MI) at week 24 of follow-up
研究概览
简要总结
This study aims to conduct a randomized controlled trial to compare the efficacy and safety of Baricitinib and Adalimumab (ADA) in the treatment of refractory intestinal Behçet's Syndrome (BS). The objective is to demonstrate if Baricitinib is non-inferior to ADA in controlling BS inflammation, reducing BS recurrence， alleviating gastrointestinal symptoms and promoting intestinal mucosal healing.
详细描述
The non-inferiority will be established by comparing the lower bound of the two-sided 95% confidence interval with the non-inferiority margin. If the lower bound was larger than the margin, Baricitinib would be regarded as non-inferiror to ADA. Superority will be further assessed in case that the non-inferiority is established. Both ITT and PP analysis will be conducted for the primary outcome given the non-inferiority design. Trial result will be primarily interpreted based on ITT analysis.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Refer to the consensus on the diagnosis and treatment of intestinal Behçet's syndrome in China: Patients who meet the 2013 International Criteria for Behçet's Disease (ICBD) and have typical Behçet's syndrome-related intestinal ulcers confirmed by colonoscopy, or patients diagnosed according to the criteria for Behçet's syndrome established by the Korean Behçet's Disease Collaborative Group in 2009;
- •Patients have a DAIBD score ≥ 40 points or intestinal symptom score ≥ 3 points at baseline;
- •Endoscopic examination conducted within 60 days before inclusion suggests active intestinal ulcers;
- •Patients who have been treated with medium to high-dose steroids (prednisolone equivalent of 0.5-1 mg/kg/day) for more than 1 month continuously, or any immunomodulator/Immunosuppressants for more than 3 months regularly or biologics for more than 2 months, as judged by the doctor to be treatment failure or intolerance;
- •Currently steroid dose ≤ 30 mg prednisolone equivalent, stabilized for ≥ 2 weeks, and/or stabilized immunomodulator dose for ≥ 4 weeks;
- •Understanding the research process, voluntary participation, and signing of informed consent.
排除标准
- •Diagnosis of other diseases such as Crohn's disease, ulcerative colitis, lymphoma, etc.;
- •Other active organ damage related to BS requires intensified immunosuppressive therapy, including aneurysms, uveitis, and substantial involvement of the central nervous system; skin lesions and joint involvement can be included;
- •Severe organ dysfunction including ALT, AST, TBIL levels exceeding twice the upper limit of normal, creatinine levels exceeding 1.5 times the upper limit of normal, white blood cell count < 3×10^9/L, ANC < 2×10^9/L, hemoglobin < 80g/L, platelets < 100×10^9/L;
- •Active infections such as active tuberculosis, active hepatitis B or C, syphilis, chronic Epstein-Barr virus infection, HIV infection, sustained or severe bacterial or viral infections, and history of severe herpes zoster;
- •Patients with latent tuberculosis must undergo ≥3 weeks of prophylactic anti-tuberculosis treatment before inclusion;
- •Primary immunodeficiency disease;
- •History of cancer, or endoscopic intestinal histopathology indicating intraepithelial neoplasia or malignancy, or presence of other malignancies;
- •Patients who did not respond to infliximab treatment for primary refractory BS (patients with secondary failure, intolerance, or allergy to infliximab should be included);
- •Patients treated with biologics/small molecule targeting therapies within 5 half-lives (including use of tofacitinib within 10 days, etanercept within 4 weeks, infliximab within 8 weeks, golimumab, certolizumab, abatacept, and tocilizumab within 10 weeks, ustekinumab within 6 months);
- •Patients with prior use of baricitinib or ADA;
- •Complications of intestinal BS such as symptomatic stenosis, short bowel syndrome, intestinal fistula, or suspected intra-abdominal abscess; potential need for surgery or situations not conducive to DAIBD and efficacy assessment; any form of intestinal resection or other abdominal surgery within 6 months before baseline; presence of a functioning (i.e., patent) stoma or ostomy;
- •Patients requiring parenteral nutrition due to disease severity;
- •Pregnant, lactating, or planning pregnancy soon;
- •Patients unwilling or unable to comply with regular visits;
- •History of severe thrombotic events or chronic cardiovascular events.
研究组 & 干预措施
Baricitinib for IBS
干预措施: Baricitinib (Drug)
Adalimumab for IBS
干预措施: Adalimumab (Drug)
结局指标
主要结局
Proportion of patients with marked improvement (MI) at week 24 of follow-up
时间窗: Baseline to week 24
Based on the combined assessment of gastrointestinal symptoms and endoscopy scores\[1\], gastrointestinal symptom scoring is defined as follows: 0 points, asymptomatic; 1 point, does not affect daily life; 2 points, mildly affects daily life; 3 points, moderately affects daily life; 4 points, severely affects daily life. Endoscopy scoring is defined as follows: 0 points, mucosal healing; 1 point, maximum ulcer ≤ original 1/4; 2 points, maximum ulcer between original 1/4 and 1/2; 3 points, maximum ulcer ≥ original 1/2 or enlargement. Marked improvement is defined as gastrointestinal symptom and endoscopy scores both ≤ 1. \[1\]Sugimura, N. et al. Real-world efficacy of adalimumab and infliximab for refractory intestinal Behçet's disease. Dig. Liver Dis. 51, 967-971 (2019).
次要结局
- Changes in SF-36 of life questionnaires compared to baseline(Baseline to week 24)
- Proportion of patients with CR (complete response) at week 24 of follow-up(Baseline to week 24)
- Proportion of patients with improvement of ≥1 point in gastrointestinal symptom scores compared to baseline at week 24 of follow-up(Baseline to week 24)
- Changes in C-reactive protein (CRP) compared to baseline(Baseline to week 24)
- Changes in erythrocyte sedimentation rate (ESR) compared to baseline(Baseline to week 24)
- Changes in DAIBD scores compared to baseline(Baseline to week 24)
- Changes in BDCAF scores compared to baseline(Baseline to week 24)
- Changes in IBDQ quality of life questionnaires compared to baseline(Baseline to week 24)
- Incidence of Treatment-Emergent Adverse Events(Baseline to week 24)