A Two-Part, Randomized, Open-label, Multicenter, Phase 2a/2b Study of the Efficacy, Safety, and Pharmacokinetics of KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera
试验速览
- 阶段
- 2 期
- 入组人数
- 20
- 试验地点
- 16
- 主要终点
- Proportion of patients with splenomegaly achieving a response at Week 32
研究概览
简要总结
This study evaluates KRT-232, a novel oral small molecule inhibitor of MDM2, for the treatment of patients with phlebotomy-dependent polycythemia vera (PV). Inhibition of MDM2 in PV is a new mechanism of action in PV. In Part A, patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon. In Part B, patients must be resistant or intolerant to hydroxyurea.
This study is a global, open-label Phase 2a/2b study to determine the efficacy and safety of KRT-232. In Part A of the study, patients will be randomly assigned to 5 arms with 2 different doses and 3 different dosing schedules of KRT 232. In Part B of the study, patients will be randomized either to treatment with KRT-232 administered at the recommended dose and schedule from Part A or to treatment with ruxolitinib.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of PV (WHO 2016)
- •Part A: patients with and without splenomegaly are eligible
- •Part A: patients must be resistant or intolerant to hydroxyurea or have undergone treatment with interferon
- •Part B: only patients with splenomegaly are eligible
- •Part B: patients must be resistant or intolerant to hydroxyurea
排除标准
- •Diagnosis of post-PV myelofibrosis (IWG-MRT)
- •Prior treatment with MDM2 inhibitors, p53-directed therapies, HDAC, BCL 2 inhibitors
- •Splenic irradiation within 3 months prior to the first dose of study treatment
- •Clinically significant thrombosis within 3 months of screening
- •Grade 2 or higher QTc prolongation
- •Part B: prior treatment with a JAK inhibitor
研究组 & 干预措施
Part B KRT-232 Arm
Recommended KRT-232 dose and schedule from Part A
干预措施: KRT-232 (Drug)
Part B Ruxolitinib Arm
Ruxolitinib per approved prescribing label
干预措施: Ruxolitinib (Drug)
Part A Arm 3
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
干预措施: KRT-232 (Drug)
Part A Arm 1
KRT-232 120mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
干预措施: KRT-232 (Drug)
Part A Arm 2
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-21 (21-day cycles)
干预措施: KRT-232 (Drug)
Part A Arm 4b
KRT-232 240mg by mouth once daily for Days 1-5, off treatment for Days 6-28 (28-day cycles)
干预措施: KRT-232 (Drug)
Part A Arm 2b
KRT-232 240mg by mouth once daily for Days 1-7, off treatment for Days 8-28 (28-day cycles)
干预措施: KRT-232 (Drug)
结局指标
主要结局
Proportion of patients with splenomegaly achieving a response at Week 32
时间窗: 32 weeks
Response defined as having achieved both of the following: * The absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32, with no more than one phlebotomy eligibility occurring post-randomization and prior to the Week 8 visit * A reduction in spleen volume as assessed by MRI (or CT) ≥ 35% from baseline at Week 32
次要结局
- Duration of response after achieving both the absence of phlebotomy eligibility and reduction in spleen volume (for patients with splenomegaly)(4 years)
- Duration of response after achieving phlebotomy independence(4 years)
- Change from baseline of MPN-SAF TSS v2.0 patient-reported outcome(32 weeks)
- Change from baseline of EORTC-QLQ-C30 patient-reported outcome(32 weeks)