A Phase 3, Randomized, Open-label, Active-Comparator-Controlled Clinical Study to Evaluate the Safety and Efficacy of Bomedemstat (MK-3543/IMG-7289) Versus Best Available Therapy (BAT) in Participants With Essential Thrombocythemia Who Have an Inadequate Response to or Are Intolerant of Hydroxyurea
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 340
- 试验地点
- 324
- 主要终点
- Durable Clinicohematologic Response (DCHR) Rate
研究概览
简要总结
This is a study evaluating the safety and efficacy of bomedemstat (MK-3543) compared with the best available therapy (BAT) in participants with essential thrombocythemia (ET) who have an inadequate response to or are intolerant of hydroxyurea. The primary study hypothesis is that bomedemstat is superior to the best available therapy with respect to durable clinicohematologic response (DCHR).
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
- •Has a diagnosis of ET per WHO 2016 diagnostic criteria for myeloproliferative neoplasms (confirmed by a central pathologist)
- •Has a centrally assessed bone marrow fibrosis score of Grade 0 or Grade 1, as per a modified version of the European Consensus Criteria for Grading Myelofibrosis
- •Has a history of inadequate response to or intolerance of hydroxyurea based on modified European LeukemiaNet (ELN) criteria for hydroxyurea resistance or intolerance
- •Has an inadequate or loss of response to their most recent prior ET therapy, requiring a change of cytoreductive therapy
- •Has a platelet count > 450 × 10^9/L (450k /μL) assessed up to 72 hours before first dose of study intervention
- •Has an absolute neutrophil count (ANC) ≥0.75 × 10^9/L assessed up to 72 hours before first dose of study intervention
- •Participants may have received up to 3 prior ET-directed cytoreductive agents including hydroxyurea
排除标准
- •Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or lysine demethylase or monoamine oxidase inhibitor (LSDi or MAOi) or the chosen best available therapy (including anagrelide, interferon alfa/pegylated interferon, ruxolitinib, or busulfan) that contraindicates participation
- •History of any illness/impairment of GI function that might interfere with drug absorption (eg, chronic diarrhea or history of gastric bypass surgical procedure), confound the study results or pose an additional risk to the individual by participation in the study
- •Evidence at the time of Screening of increased risk of bleeding
- •History of a malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder
- •Human immunodeficiency virus (HIV)-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
研究组 & 干预措施
Bomedemstat
Participants will begin treatment at a dose of 50 mg of bomedemstat daily. Dosage will be adjusted either up or down within specified time parameters for each participant to the dose that provides sufficient exposure to safely inhibit thrombopoiesis to decrease platelet counts to the target range. All participants will be treated daily for up to 52 weeks and are eligible for an extended treatment phase up to an additional 156 weeks.
干预措施: Bomedemstat (Drug)
Best Available Therapy
Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b, or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to 52 weeks. Participants receiving BAT for 52 weeks who stop responding to BAT are eligible to switch to bomedemstat and receive this for up to 156 weeks at the investigator's discretion.
干预措施: Interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b (Drug)
Best Available Therapy
Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b, or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to 52 weeks. Participants receiving BAT for 52 weeks who stop responding to BAT are eligible to switch to bomedemstat and receive this for up to 156 weeks at the investigator's discretion.
干预措施: Anagrelide (Drug)
Best Available Therapy
Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b, or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to 52 weeks. Participants receiving BAT for 52 weeks who stop responding to BAT are eligible to switch to bomedemstat and receive this for up to 156 weeks at the investigator's discretion.
干预措施: Busulfan (Drug)
Best Available Therapy
Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b, or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to 52 weeks. Participants receiving BAT for 52 weeks who stop responding to BAT are eligible to switch to bomedemstat and receive this for up to 156 weeks at the investigator's discretion.
干预措施: Ruxolitinib (Drug)
结局指标
主要结局
Durable Clinicohematologic Response (DCHR) Rate
时间窗: Up to approximately 52 weeks
DCHR rate is the percentage of participants with DCHR, defined as a confirmed reduction of platelet count to ≤400 × 10\^9/L and absence of white blood cell (WBC) count elevation to \>10 × 10\^9/L locally assessed to be due to ET, starting by Week 24 and maintained for at least 24 weeks, and the absence of any thrombotic or major hemorrhagic events or disease progression to myelofibrosis (MF), myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) by Week 52.
次要结局
- Change From Baseline in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Individual Fatigue Symptom Item Score(Baseline and pre-specified timepoints through Week 156)
- Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score(Baseline and pre-specified timepoints through Week 156)
- Change From Baseline in Total Symptom Score as Measured on the MFSAF v4.0(Baseline and pre-specified timepoints through Week 156)
- Duration of Hematologic Remission (DOHR)(Up to approximately 52 weeks)
- Percentage of Participants with Thrombotic Events(Up to 156 weeks)
- Percentage of Participants with Major Hemorrhagic Events(Up to 156 weeks)
- Disease Progression Rate(Up to approximately 52 weeks)
- Number of Participants with An Adverse Event (AE)(Up to 180 weeks)
- Number of Participants Discontinuing From Study Therapy Due to an AE(Up to 152 weeks)
- Duration of Clinicohematologic Response (DOCHR)(Up to approximately 52 weeks)
- Clinicohematologic Response (CHR) Rate(Up to approximately 52 weeks)
- Hematologic Response (HR) Rate(Up to approximately 52 weeks)
- Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score(Baseline and pre-specified timepoints through Week 52)
- Change From Baseline in Total Symptom Score as Measured on the MFSAF v4.0(Baseline and pre-specified timepoints through Week 52)
- Duration of Durable Clinicohematologic Response (DODCHR)(Up to approximately 52 weeks)
- Duration of Hematologic Response (DOHR)(Up to approximately 52 weeks)
- Percentage of Participants with Thrombotic Events(Up to approximately 52 weeks)
- Percentage of Participants with Major Hemorrhagic Events(Up to approximately 52 weeks)
- Percentage of Participants with Disease Progression to Post-ET MF or MDS/AML(Up to approximately 52 weeks)
- Number of Participants with An Adverse Event (AE)(Up to approximately 52 weeks)
- Number of Participants Discontinuing From Study Therapy Due to an AE(Up to approximately 52 weeks)