Low-dose Baricitinib Plus High-dose Dexamethasone as First-line Treatment for Patients With Newly Diagnosed Immune Thrombocytopenia: a Multicenter, Open-label, Randomized, Controlled, Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 132
- 试验地点
- 10
- 主要终点
- Durable response
研究概览
简要总结
A randomized, open-label, multicenter, phase 2 trial to compare the efficacy and safety of baricitinib plus high-dose dexamethasone compared to high-dose dexamethasone monotherapy for the first-line treatment of adults with primary immune thrombocytopenia (ITP).
详细描述
This is a parallel group, multicenter, randomized, controlled trial of patients with ITP in China. Patients were randomly assigned to receive baricitinib plus high-dose dexamethasone or high-dose dexamethasone monotherapy. Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request. The primary endpoint is durable response, defined as the maintenance of platelet count ≥30,000/μL and at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed newly-diagnosed, treatment-naive ITP;
- •A platelet count <30,000/μL, or a platelet count <50,000/μL with clinically significant bleeding symptoms (WHO bleeding scale 2 or above) at the enrollment;
- •Willing and able to sign written informed consent.
排除标准
- •Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
- •Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test;
- •Active or a history of malignancy;
- •Pregnancy or lactation;
- •Received first-line and second-line ITP-modifying therapy;
- •Previously received corticosteroids or immunosuppressive agents for non-ITP diseases within 6 months before enrollment;
- •A history of clinically significant adverse reactions to previous corticosteroid therapy;
- •Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia);
- •Current or recent (<4 weeks prior to screening) clinically serious viral, bacterial, fungal, or parasitic infection;
- •A history of symptomatic herpes zoster infection within 12 weeks prior to screening;
- •Active or chronic viral infection from hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV);
- •Have evidence of active tuberculosis (TB), or have previously had evidence of active TB and did not receive appropriate and documented treatment, or have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB;
- •Have experienced a clinically significant thrombotic event within 24 weeks of screening or are on anticoagulants and in the opinion of the investigator are not well controlled;
- •Myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage IV heart failure;
- •A history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute an unacceptable risk when taking investigational product or interfere with the interpretation of data;
- •Any of the following specific abnormalities on screening laboratory tests:
- •ALT or AST >2 x ULN, or total bilirubin ≥1.5 x ULN 2) hemoglobin <9 g/dL, or total white blood cell (WBC) count <2,500/µL, or neutropenia (absolute neutrophil count <1,200/µL), or lymphopenia (lymphocyte count <750/µL) 3) eGFR <50 mL/min/1.73 m^2.
研究组 & 干预措施
Low-dose baricitinib plus high-dose dexamethasone
Oral baricitinib is given at a dose of 2 mg daily for 6 consecutive months. Dexamethasone is administrated at 40 mg per day for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10). Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request.
干预措施: Baricitinib 2 MG (Drug)
Low-dose baricitinib plus high-dose dexamethasone
Oral baricitinib is given at a dose of 2 mg daily for 6 consecutive months. Dexamethasone is administrated at 40 mg per day for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10). Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request.
干预措施: Dexamethasone (Drug)
High-dose dexamethasone
Dexamethasone is administrated at 40 mg per day for 4 consecutive days (the 4-day course of dexamethasone will be repeated in the case of lack of response by day 10). Treatment will be discontinued if very severe or life-threatening adverse events developed or at the patients' request.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Durable response
时间窗: 6 months
The maintenance of a platelet count ≥30,000/μL, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up.
次要结局
- Response (R)(1 month)
- Complete response (CR)(1 month)
- Time to response(6 months)
- Duration of response(6 months)
- Early response(7 days)
- Initial response(28 days)
- Bleeding events(From the start of study treatment (Day 1) to the end of week 26)
- Health-related quality of life (HRQoL)(From the start of study treatment (Day 1) to the end of week 26)
- Adverse events(From the start of study treatment (Day 1) to the end of week 26)
研究者
Xiao Hui Zhang
Vice president of Peking Univeristy Institute of Hematology
Peking University People's Hospital