A Phase 2 Open-Label, Dose-Ranging Study of the Efficacy and Safety of Orally Administered SAR302503 in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8
- 试验地点
- 7
- 主要终点
- Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction as measured by MRI (or CT scan in subjects with contraindications for MRI). - Time Frame:
研究概览
简要总结
Primary Objective:
- To evaluate the efficacy of daily oral doses of 300 mg, 400 mg, and 500 mg SAR302503 and combined for the response rate defined with the ≥35% reduction of spleen volume as determined by magnetic resonance imaging (MRI or computed tomography scan [CT] in patients with contraindications for MRI).
Secondary Objectives:
- To evaluate the safety of SAR302503 for both pooled (300, 400, and 500mg) and individual doses population.
- To evaluate the pharmacokinetics (PK) of SAR302503 after single and repeat-dose.
- To evaluate the effect on Myelofibrosis (MF)-associated symptoms (Key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF).
- To evaluate the durability of splenic response.
- To evaluate the effect of SAR302503 on bone marrow with regard to changes on reticulin fibrosis.
详细描述
The duration of the study for an individual patient will include a period to assess eligibility (screening period 28 days), followed by a treatment period of at least 1 cycle (28 days) of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue if patients are deriving benefit and do not have unacceptable toxicity or meet study withdrawal criteria.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
SAR302503 300mg
SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 300mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
干预措施: SAR302503 (Drug)
SAR302503 400 mg
SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 400 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
干预措施: SAR302503 (Drug)
SAR302503 500 mg
SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 500 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
干预措施: SAR302503 (Drug)
结局指标
主要结局
Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction as measured by MRI (or CT scan in subjects with contraindications for MRI). - Time Frame:
时间窗: 24 weeks
次要结局
- Percent change from baseline in spleen volume measured by MRI(24 weeks)
- Duration of maintenance of ≥35% reduction in spleen volume(From baseline to the 30 days after last drug administration)
- Number of patients with Serious Adverse events using NCI CTCAE v4.03, clinical parameters and vital signs(From baseline to the 30 days after last drug administration)
- Measurements of SAR302503 pharmacokinetic endpoints including Cmax, Tmax, and AUC0-24(SAR302503, pre-dose and post-dose plasma collections will be obtained on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 2, and Cycle 3 Day 1)
- Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction in the total symptom score using the modified MFSAF(24 weeks)
- Percent change from baseline in spleen size measured by palpation(24 weeks)
- Proportion of patients with any grade reduction in reticulin fibrosis(24 weeks)