A Phase 2/3, Randomized, Open-label, Active-comparator-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Bomedemstat (MK-3543) Versus Best Available Therapy in Participants With Polycythemia Vera Who Have an Inadequate Response to or Are Intolerant to Hydroxyurea
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 380
- 主要终点
- Clinicohematologic Response (CHR) Rate
研究概览
简要总结
Researchers are looking for new ways to treat polycythemia vera (PV). People with PV may receive treatment to lower the number of red blood cells in the blood, but the usual treatments may not work for everyone. Researchers want to learn if a trial medicine called bomedemstat, also called MK-3543, can treat PV. In this study, researchers will compare bomedemstat to 2 usual treatments for PV.
The goal of this study is to learn if more participants who take bomedemstat reach healthy blood cell counts and avoid major health problems from PV, compared to those who receive a usual treatment.
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
- •The main inclusion criteria include but are not limited to the following:
- •Has confirmed local diagnosis of polycythemia vera (PV) per World Health Organization (WHO) diagnostic criteria for PV
- •Must have discontinued prior cytoreductive therapy for condition under study for protocol specified duration
- •Has failed at least one prior line of cytoreductive therapy to lower hematocrit
- •Has a history of inadequate response, resistance to, or intolerant to hydroxyurea (HU) per protocol specified criteria
- •Has no evidence of splenomegaly and no symptoms attributable to splenomegaly, including early satiety, left upper quadrant discomfort, or splenic pain
- •Has locally assessed bone marrow (BM) fibrosis score of Grade 0 or Grade 1 as per modified version of the European Consensus Criteria for Grading Myelofibrosis
- •Human Immunodeficiency Virus (HIV)-infected participants have well controlled HIV on antiretroviral therapy (ART)
- •Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load
- •Participants with history of Hepatitis C Virus (HCV) infection are eligible if HCV viral load is undetectable
- •Participants must be able to swallow oral medication and follow instructions for at home dosing of bomedemstat
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has history of any illness/impairment of gastrointestinal (GI) function that might interfere with drug absorption
- •Has evidence at the time of screening of increased risk of bleeding
- •Has history of malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Is currently receiving anticancer therapy
- •Has an active infection requiring systemic therapy
- •Has had major surgical procedure ≤4 weeks before first dose of study intervention or has not recovered from side effects of major surgical procedure
研究组 & 干预措施
Best Available Therapy (BAT)
Participants will receive either ropeinterferon alfa-2b or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to approximately 52 weeks.
干预措施: Ruxolitinib (Drug)
Best Available Therapy (BAT)
Participants will receive either ropeinterferon alfa-2b or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to approximately 52 weeks.
干预措施: Ropeginterferon alfa-2b (Drug)
Bomedemstat
Participants will receive bomedemstat daily for up to approximately 52 weeks. Per protocol, dosage may be adjusted within specified time parameters for each participant to achieve and maintain protocol-specified platelet and hematocrit target ranges. Eligible participants who do not discontinue study treatment at Week 52, may continue to receive study treatment.
干预措施: Bomedemstat (Drug)
结局指标
主要结局
Clinicohematologic Response (CHR) Rate
时间窗: Up to approximately Week 52
CHR Rate is defined as all of the following: (i) a confirmed hematologic remission sustained for at least 12 consecutive weeks by Week 40 through Week 52, (ii) and absence of any of the following as assessed by the adjudication committee Week 52: thrombotic event; major hemorrhagic events; disease progression to myelofibrosis (MF) or myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML). CHR will begin on the date of the first confirmed assessment achieving CHR criteria and will end on the earliest date of the following: 1) day of the first confirmed assessment not achieving CHR criteria, 2) date of first major hemorrhagic event or thrombotic event as assessed by the adjudication committee, or 3) disease progression as assessed by the adjudication committee. The CHR rate will be presented.
次要结局
- Clinicohematologic Response Sustained for a 24-Week Time Period (CHR24)(Up to approximately Week 52)
- Number of Participants Who Experience an Adverse Event (AE)(Up to approximately Week 52)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately Week 52)
- Duration of Clinicohematologic Response Sustained for a 24-Week Time Period (DOCHR24)(Up to approximately Week 52)
- Duration of Clinicohematologic Response (DOCHR)(Up to approximately Week 52)
- Duration of Hematologic Remission (DOHR)(Up to approximately Week 52)
- Number of Participants Who Experience Phlebotomies(Up to approximately Week 52)
- Disease Progression Rate(Up to approximately Week 52)
- Number of Participants Who Experience Thrombotic Events(Up to approximately Week 52)
- Number of Participants Who Experience Major Hemorrhagic Events(Up to approximately Week 52)
- Change From Baseline in Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4) Total Symptom Score(Up to approximately Week 52)
- Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Total Fatigue Score(Up to approximately Week 52)