Safety and Tolerability of Tofacitinib in the Treatment of Rheumatoid Arthritis-related Interstitial Lung Disease (RAILDTo Trial).
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Incidence and severity of adverse events
研究概览
简要总结
Nowadays, no single drug is approved to treat rheumatoid arthritis-related interstitial lung disease (RA-ILD). The medical management of this clinical condition is empirical and controversial. There is preliminary data that tofacitinib may have a beneficial effect in treating RA-ILD. Tofacitinib may have a double role in treating RA-ILD: treat RA disease activity and an anti-fibrotic possible impact. Moreover, tofacitinib may be used as monotherapy for the treatment of rheumatoid arthritis (RA) This is a phase IIa clinical trial to evaluate the safety and tolerability of tofacitinib in RA-ILD patients.
详细描述
This is a phase 2 open-label study designed to evaluate the safety and tolerability of tofacitinib in RA-ILD patients. Patients who met the inclusion criteria of the study protocol will receive tofacitinib 5 mg BID for 12 months.
Objectives
Primary objectives:
- To evaluate the safety and tolerability of tofacitinib 5 mg PO BID as monotherapy for managing RA-ILD in RA-ILD patients.
- To evaluate the pulmonary function of patients treated with tofacitinib PO BID as monotherapy to manage RA-ILD in RA-ILD patients, at baseline, at three months of follow-up, at six months of follow-up, and one year of follow-up.
- To estimate the efficacy of tofacitinib 5 mg PO BID as monotherapy for the management of RA-ILD, in RA-ILD patients, at three months of follow-up, at six months of follow-up, and at one year of follow-up, according to the ACR 20, 50, 70 response criteria, and the following disease activity scores index: DAS 28, CDAI and SDAI.
All the included patients will receive Tofacitinib in doses of 5 mg BID until the end of the protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study
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
- •Patients must fulfill ACR/EULAR 2010 RA classification criteria.
- •Patients must have an interstitial lung disease confirmed by a high-resolution computed tomography scan or a surgical lung biopsy. Nonspecific interstitial pneumonia, usual interstitial pneumonia, lymphocytic pneumonia, and organized pneumonia, either by HRCT or surgical biopsy, will be included.
- •Patients must be 18 years of age or older.
- •There is no evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB).
- •Patients must discontinue using the non-permitted medications: leflunomide, azathioprine, cyclosporine, tacrolimus, cyclophosphamide, and any biologic disease-modifying drug (bDMDARDs) such as anti-TNF therapy, rituximab, tocilizumab, etc. Patients must have a stable prednisone dose of ≤ 10 mg/ PO/day for at least three months.
- •All patients must have stable doses of prednisone during the last three months of follow-up, and the prednisone dose must be ≤ 10 mg/day. Patients without a prednisone history in the previous three months may also be included in the protocol.
排除标准
- •Seropositivity for the following infections: HIV, HBV, and HCV.
- •Absolute neutrophil count ≤ 1,200/L
- •Absolute platelet count ≤ 100,000 /L
- •Severe renal damage with GFR < 30 ml/min based on CKD-EPI formula.
- •AST or ALT greater than 1.5 times the upper limit of normal AST and ALT levels
- •Severe hepatic, hematologic, gastrointestinal, cardiac, and neurological disease may put the patient´s life at risk regardless of ILD severity.
- •Severe active infections at baseline evaluation, such as pneumonia, urinary tract infections, meningitis.
- •8 History of drug abuse or alcoholism.
- •History of any malignancy
- •Patients with an FVC < 40% of what is expected will be excluded from the study.
研究组 & 干预措施
Tofacitinib Arm
Tofacitinib in doses of 5 mg BID, in RA-ILD patients at stable doses of prednisone ≤ 10 mg/day during the last three months.
干预措施: Tofacitinib (Drug)
结局指标
主要结局
Incidence and severity of adverse events
时间窗: 52 weeks
Adverse event: Any untoward medical occurrence in a subject being included in the trial, in which the event may not necessarily have a causal relationship with the treatment. Examples of adverse events are as follows: abnormal test findings, clinically significant symptoms and signs, hypersensitivity reactions, and progression or worsening of RA or RA-ILD.
次要结局
- 6 minutes walk test(52 weeks)
- Rheumatoid arthritis disease activity according to the simplified disease activity (SDAI) index.(52 weeks)
- Rheumatoid arthritis disease activity according to the Disease Activity Score Index (DAS28)(52 weeks)
- Forced Vital Capacity (liters)(52 weeks)
- Carbon monoxide diffusing capacity (DLCO) (mil/min/mmHg)(52 weeks)