A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)
研究概览
简要总结
Patients with severe thalassemia (thalassemia major) present with severe anemia that required life-long transfusion therapy, spleen enlargement that led to increased transfusion requirement, and other serious complications as early death, growth retardation, bone deformations and iron overload due to blood transfusions. Splenectomy can significantly reduce transfusion requirement in thalassemia patients, but it is associated with an increased risk of serious complications such as sepsis and thrombosis. Preliminary preclinical and clinical data suggested that JAK2 inhibition, by reducing spleen size, could improve hemoglobin levels, thereby eliminating the need for splenectomy and reducing transfusion requirement and related iron overload.
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
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 with thalassemia on a regular and stable transfusion regimen (at least 2 RBC units within every 4-week interval for 24 weeks prior to Screening) and anticipated to receive the same transfusion regimen during the study.
- •Patients with spleen enlargement at Screening, defined as spleen palpable below the costal margin and spleen volume of ≥ 450 cm3 as confirmed by MRI (or CT scan in applicable patients).
- •Patients need to be on iron chelation treatment (deferoxamine or deferasirox) for at least four weeks prior to Screening
排除标准
- •Splenectomy prior to or planned during the study
- •Active serious bacterial, mycobacterial, fungal, parasitic or viral infection which requires therapy (e.g., pneumonia, tuberculosis, systemic mycosis, herpes zoster)
- •Hemoglobin <65 g/L (<4.0 mmol/L) at Screening
- •Platelet count <75×109/L, absolute neutrophils count < 1.5×109/L at Screening.
- •Estimated MDRD < 30 mL/min/1.73 m2 at Screening.
- •ALT (SGPT) levels >5 times ULN at Screening.
- •Hepatocellular disease such as hepatitis B (presence of HBs antigen), hepatitis C (presence of HCV RNA), liver cirrhosis.
- •HIV positivity
研究组 & 干预措施
INC424 (ruxolitinib) - Study Treatment
Regularly transfused adult patients with thalassemia and spleen enlargement.
干预措施: ruxolitinib (Drug)
结局指标
主要结局
Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)
时间窗: week 6 to week 30 interval
Change of RBC transfusion requirement measured as percent change of the hematocrit-adjusted volume of transfused RBC and observed during within on-treatment interval (any time-points of RBC transfusion between week 6 and week 30 driven by the individual patient's need) compared to baseline (defined by pre-treatment interval between Week - 24 to start of treatment).
次要结局
- Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals(baseline, weeks 0 - 30)
- Percentage Change in Spleen Length (cm) Below the Left Coastal Margin(baseline, weeks 1,2,3,4,6,12,18,24,30)
- Pharmacokinetics (PK) Parameter of Cmin(week 2, week 12)
- Percentage Change in Spleen Volume (cm3)(baseline, week 12, week 30)
- Pharmacokinetics (PK) Parameter of Cmax(Day 1, Week 2 (Day 15), Week 12 (Day 85))