A Phase 3, Randomized, Double-blind Active-controlled Study Evaluating Momelotinib vs. Ruxolitinib in Subjects With Primary Myelofibrosis (PMF) or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 432
- 主要终点
- Splenic Response Rate at Week 24
研究概览
简要总结
This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib (RUX) in participants with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF) who have not yet received treatment with a Janus kinase inhibitor (JAK inhibitor).
Participants will be randomized to receive either MMB or ruxolitinib for 24 weeks during a double-blind treatment phase, after which they will be eligible to receive open-label MMB for up to an additional 216 weeks. After discontinuation of study medication, assessments will continue for 12 additional weeks, after which participants will be contacted for survival follow-up approximately every 6 months for up to 5 years from the date of enrollment or until study termination. For those participants planning to continue treatment with MMB following the end of the study, the Early Study Drug Discontinuation (ESDD), 30-day, 12-Week, and survival follow-up visits are not required.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Palpable splenomegaly at least 5 cm below the left costal margin
- •Confirmed diagnosis of PMF or post-PV/ET MF
- •Requires myelofibrosis therapy, in the opinion of the investigator
- •Classified as high risk OR intermediate-2 risk as defined by the International Prognostic Scoring System (IPSS) for PMF, or intermediate-1 risk (IPSS) associated with symptomatic splenomegaly, hepatomegaly, anemia (hemoglobin < 10.0 g/dL), and/or unresponsive to available therapy
- •Acceptable laboratory assessment obtained within 14 days prior to the first dose of study drug:
- •Absolute neutrophil count (ANC) ≥ 0.75 x 10^9/L in the absence of growth factor in the prior 7 days
- •Platelet Count ≥ 50 x 10^9/L (≥ 100 x 10^9/L if aspartate aminotransferase [AST] or alanine aminotransferase [ALT] is ≥ 2 x the upper limit of the normal range [ULN]) in the absence of platelet transfusion(s) or thrombopoietin mimetics in the prior 7 days
- •Peripheral blood blast count < 10%
- •AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
- •Calculated creatinine clearance (CrCL) of ≥ 45 mL/min
- •Direct bilirubin ≤ 2.0 x ULN
- •Life expectancy of > 24 weeks
- •Males and females of childbearing potential 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 understand and willing to sign the informed consent form
排除标准
- •Prior splenectomy
- •Splenic irradiation within 3 months prior to the first dose of study drug
- •Eligible for allogeneic bone marrow or stem cell transplantation
- •Uncontrolled inter-current illness, per protocol.
- •Known positive status for human immunodeficiency virus (HIV)
- •Chronic active or acute viral hepatitis A, B, or C infection, or a hepatitis B or C carrier
- •Prior use of a JAK1 or JAK2 inhibitor
- •Use of chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or investigational therapy within 4 weeks of the first dose of study drug
- •Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
- •Unwilling or unable to undergo a magnetic resonance imaging (MRI) or computed tomography (CT) scan
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Momelotinib
Participants will receive momelotinib plus placebo to match ruxolitinib.
干预措施: Momelotinib (Drug)
Momelotinib
Participants will receive momelotinib plus placebo to match ruxolitinib.
干预措施: Placebo to match ruxolitinib (Drug)
Ruxolitinib
Participants will receive ruxolitinib plus placebo to match momelotinib.
干预措施: Ruxolitinib (Drug)
Ruxolitinib
Participants will receive ruxolitinib plus placebo to match momelotinib.
干预措施: Placebo to match momelotinib (Drug)
结局指标
主要结局
Splenic Response Rate at Week 24
时间窗: Week 24
Splenic response rate at Week 24 is defined as the percentage of participants who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT.
次要结局
- Rate of Red Blood Cell (RBC) Transfusions in the Double-blind Phase, (the Average Number of RBC Units Transfused Per Month Not Associated With Overt Bleeding)(Baseline to Week 24)
- Total Symptom Score (TSS) Response Rate at Week 24(Week 24)
- RBC Transfusion Independence Rate at Week 24, (Defined as Absence of RBC Transfusions and no Hemoglobin Level Below 8 g/dL in the 12 Weeks Prior to Week 24, Excluding Cases Associated With Clinically Overt Bleeding)(Week 24)
- RBC Transfusion Dependence Rate at Week 24. (Defined as Having Had at Least 4 Units of RBC Transfusions, or a Hemoglobin Level Below 8 g/dL in 8 Weeks Prior to Week 24 (Excluding Cases Associated With Clinically Overt Bleeding)).(Week 24)