A Phase 2b, Open-label, Multicenter, Randomized, Controlled, 2-Arm Study to Assess the Efficacy and Safety of Orally Administered NS-018 Versus Best Available Therapy in Subjects With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Severe Thrombocytopenia (Platelet Count <50,000/μL)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 51
- 主要终点
- Change in Spleen Volume
研究概览
简要总结
This study will enroll male and female subjects who are 18 years of age or older with Primary Myelofibrosis, post-polycythemia Vera Myelofibrosis, or post-essential Thrombocythemia Myelofibrosis with severe thrombocytopenia (platelet count <50,000/µL) including subjects with intermediate-2 or high-risk MF according to the Dynamic International Prognostic Scoring System (DIPSS).
详细描述
NS-018 will be self-administered orally at a dose of 300 mg BID. The BAT will be administered according to manufacturer's instructions and Investigator discretion. Subjects will complete study visits at Screening, Day 1 and Day 15 of Cycle 1, 2, 3, 4, 5, 6 and Day 1 of every cycle thereafter. At these visits, blood/urine sampling, spleen measurements, bone marrow assessments, patient-reported outcome (PRO) assessments, and safety assessments may be performed.
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
- Single (Outcomes Assessor)
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
- •Primary MF, post-PVMF or post-ETMF according to the DIPSS risk categories of intermediate-2 or high-risk MF
- •Average platelet count of <50,000/µL at Screening based on 2 measurements taken on different days; both measurements must be <50,000/µL.
- •ECOG performance status ≤
- •Life expectancy >6 months.
- •Spleen volume of at least 450 cm3 measured by MRI (or by CT for applicable subjects).
- •Total Symptom Score (TSS) ≥10 on the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.
- •Peripheral blast count <10%.
- •No MF-directed treatment for at least 2 weeks prior to initiation of NS-018, including JAK inhibitor, erythropoietic, thrombopoietic agent, or any use of corticosteroids for MF symptom or blood count management. Low dose corticosteroids <10 mg/day prednisone or equivalent is allowed for non-MF purposes.
排除标准
- •Active, uncontrolled systemic infection.
- •Any prior treatment with more than two JAK inhibitors.
- •Previous treatment with NS-
- •Subjects actively receiving a concurrent investigational agent.
- •Subjects with any unresolved AE greater than Grade 1 other than hematological AEs from previous anticancer therapy.
- •Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 (see Appendix 5) or taking medication known to be strong inhibitors or inducers of CYP3A4 (see Appendix 5).
- •Radiation therapy for splenomegaly within 6 months prior to study entry (screening).
- •History of splenectomy or planning to undergo splenectomy.
- •Subjects with a serious cardiac condition within the past 6 months such as uncontrolled arrhythmias, myocardial infarction, angina or heart disease
- •Subjects diagnosed with another malignancy within 2 years prior to an enrollment.
- •Subjects who have had surgery (other than placement of vascular access and bone marrow biopsy) within 4 weeks of study entry (screening), or subjects with incomplete recovery from any prior surgical procedures.
研究组 & 干预措施
NS-018
Self-administered NS-018 300 mg orally, twice daily, preferably at the same time each day in consecutive 4-week (28-day) cycles
干预措施: NS-018 (Drug)
Best Available Therapy (BAT)
Single agent per Investigator discretion or no therapy
干预措施: Best Available Therapy (Drug)
结局指标
主要结局
Change in Spleen Volume
时间窗: baseline and week 24
Proportion of subjects who achieve ≥35% reduction in spleen volume from baseline compared to Week 24 as measured by MRI (or by CT for applicable subjects)
Change in Total Symptom Score (TSS)
时间窗: baseline and week 24
Proportion of subjects who achieve ≥50% reduction in total symptom score from baseline compared to Week 24 as measured by the MF-SAF v4.0
次要结局
- Change in Spleen Volume(from baseline to anytime before or at week 24)
- Comparison of Treatment-emergent AEs Between NS-018 and BAT(from baseline to week 24)