A Phase 2, Open-label, Randomized Study to Evaluate the Safety and Efficacy of Momelotinib in Subjects With Polycythemia Vera or Essential Thrombocythemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 39
- 主要终点
- Overall response rate
研究概览
简要总结
This open-label study is to determine the safety and efficacy of momelotinib in participants with either polycythemia vera (PV) or essential thrombocythemia (ET) who have not yet received treatment with a Janus kinase (JAK) inhibitor.
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
- •Diagnosis of either PV or ET as defined by the 2008 World Health Organization (WHO) Diagnostic Criteria
- •Requires treatment for PV or ET, in the opinion of the study investigator
- •Intolerant of, resistant to, or refuses current or available treatment for PV or ET
- •Direct bilirubin ≤ 2.0 x upper limit of the normal range (ULN)
- •Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x ULN
- •Calculated creatinine clearance (CrCl) of ≥ 45 mL/min
- •Life expectancy > 24 weeks
- •Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
- •Females who are nursing must agree to discontinue nursing before the first dose of study drug
- •Able to comprehend and willing to sign informed consent form
排除标准
- •Prior splenectomy
- •Uncontrolled intercurrent illness, per protocol
- •Known positive status for human immunodeficiency virus (HIV)
- •Chronic active or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier
- •Myeloproliferative neoplasm-directed therapy, other than aspirin, hydroxyurea, anagrelide, and/or phlebotomy, within 21 days prior to the first dose of study drug
- •Anagrelide within 7 days prior to the first dose of study drug
- •Presence of peripheral neuropathy ≥ Grade 2
- •Unwilling or unable to take oral medication
- •Prior use of a JAK1 or JAK2 inhibitor
- •Use of strong CYP3A4 inducers within 1 week prior to the first dose of study drug
- •QTc interval > 450 msec, unless attributed to bundle branch block
研究组 & 干预措施
Momelotinib 100 mg PV
Participants with polycythemia vera will receive 100 mg of momelotinib.
干预措施: Momelotinib (Drug)
Momelotinib 200 mg PV
Participants with polycythemia vera will receive 200 mg of momelotinib.
干预措施: Momelotinib (Drug)
Momelotinib 100 mg ET
Participants with essential thrombocythemia will receive 100 mg of momelotinib.
干预措施: Momelotinib (Drug)
Momelotinib 200 mg ET
Participants with essential thrombocythemia will receive 200 mg of momelotinib.
干预措施: Momelotinib (Drug)
结局指标
主要结局
Overall response rate
时间窗: Up to 24 weeks
For the PV Cohort, overall response rate (ORR) is defined as the proportion of participants with all of the following at some point during the treatment period: * Hematocrit \< 45% in the absence of phlebotomy that lasts at least 4 weeks * White blood cell (WBC) count \< 10 x 10\^9/L that lasts at least 4 weeks * Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks * Resolution of palpable splenomegaly that lasts at least 4 weeks For the ET Cohort, overall response rate is defined as the proportion of participants with all of the following at some point during the treatment period: * WBC count \< 10 x 10\^9/L that lasts at least 4 weeks * Platelet count ≤ 400 x 10\^9/L that lasts at least 4 weeks * Resolution of palpable splenomegaly that lasts at least 4 weeks
次要结局
- Proportion of participants with ≥ 10 point decrease in modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) compared to baseline that lasts at least 12 weeks(Up to 24 weeks)
- Confirmed overall response rate(Up to 24 weeks)
- Proportion of participants with WBC < 10 x 10^9/L that lasts at least 4 weeks(Up to 24 weeks)
- Proportion of participants with resolution of palpable splenomegaly that lasts at least 4 weeks(Up to 24 weeks)
- Proportion of participants with hematocrit < 45% in the absence of phlebotomy that lasts at least 4 weeks(Up to 24 weeks)
- Proportion of participants with platelet count ≤ 400 x 10^9/L that lasts at least 4 weeks(Up to 24 weeks)