Polycythemia Vera
Conditions
Brief summary
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.
Interventions
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinicohematologic Response (CHR) Rate | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinicohematologic Response Sustained for a 24-Week Time Period (CHR24) | Up to approximately Week 52 | CHR24 is defined as all of the following: (i) a confirmed hematologic remission sustained for at least 24 consecutive weeks by 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 MF or MDS/AML. CHR24 will begin on the date of the first confirmed assessment achieving CHR24 criteria and will end on the earliest date of the following: 1) day of the first confirmed assessment not achieving CHR24 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 CHR24 will be presented. |
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately Week 52 | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience AE will be reported. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately Week 52 | An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be reported. |
| Duration of Clinicohematologic Response Sustained for a 24-Week Time Period (DOCHR24) | Up to approximately Week 52 | For participants who show CHR24, DOCHR24 is defined as the time from the first confirmed hematologic remission to first documented evidence of: 1) confirmed platelet increase, confirmed WBC increase, or a required phlebotomy (defined as a confirmed HCT reduction) after latest confirmed hematologic remission date, 2) thrombotic event as assessed by the adjudication committee, 3) major hemorrhagic event as assessed by the adjudication committee, or 4) disease progression to MF or MDS/AML as assessed by the adjudication committee. |
| Duration of Clinicohematologic Response (DOCHR) | Up to approximately Week 52 | For participants who show CHR, DOCHR is defined as the time from the first confirmed hematologic remission to first documented evidence of: 1) confirmed platelet increase, confirmed WBC increase, or a required phlebotomy (defined as a confirmed HCT reduction) after latest confirmed hematologic remission date, 2) thrombotic event as assessed by the adjudication committee, 3) major hemorrhagic event as assessed by the adjudication committee, or 4) disease progression to MF or MDS/AML as assessed by the adjudication committee. |
| Duration of Hematologic Remission (DOHR) | Up to approximately Week 52 | For participants who show confirmed hematologic remission, DOHR is defined as the time from the first hematologic remission until loss of hematologic remission. |
| Number of Participants Who Experience Phlebotomies | Up to approximately Week 52 | Per protocol, a required phlebotomy is defined as confirmed hematocrit (HCT) ≥45% with a ≥3% increase from baseline HCT or confirmed HCT ≥48%. The number of participants who experienced phlebotomies will be presented. |
| Disease Progression Rate | Up to approximately Week 52 | Disease progression is defined as the transformation to post polycythemia vera myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia as assessed by the adjudication committee. The disease progression rate will be presented. |
| Number of Participants Who Experience Thrombotic Events | Up to approximately Week 52 | Thrombotic events are defined as new or recurrent acute myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), deep venous thrombosis (DVT), pulmonary embolism (PE), thrombotic digital ischemia, other thrombotic events such as peripheral limb ischemia or Budd-Chiari syndrome assessed to be due to underlying polycythemia vera (PV), and other vascular occlusive events such as symptoms of cardiac, abdominal, or peripheral limb ischemia supported by objective evidence of vessel disease and/or ischemia. The number of participants who experience thrombotic events will be presented. |
| Number of Participants Who Experience Major Hemorrhagic Events | Up to approximately Week 52 | Major hemorrhagic events include but are not limited to fatal bleeding, symptomatic bleeding in a critical area or organ (including intracranial, intraspinal, intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome), or bleeding causing a decrease in hemoglobin of 2 g/dL or more or leading to transfusion of 2 or more units of whole blood or red cells, and clinically relevant non-major bleeding events leading to hospitalization or increased level of care or clinically important bleeding prompting a face-to-face medical evaluation. |
| Change From Baseline in Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4) Total Symptom Score | Up to approximately Week 52 | The MFSAF v4.0 is a 7-item participant-reported symptom assessment that asks respondents to report symptom severity at its worst for each of the 7 items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale. The MFSAF v4.0 7-day recall format is used. Individual symptoms are assessed on an 11-point numeric rating scale with a total symptom score range of 0 (absent) to 70 (worst imaginable). The change from baseline in MFSAF total score for all symptoms will be presented |
| Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Total Fatigue Score | Up to approximately Week 52 | The PROMIS Fatigue SF is a 7-item participant-reported assessment that measures both the experience of fatigue and the interference of fatigue on daily activities over the past week. Response options are on a 5-point Likert scale, ranging from 1 (never) to 5 (always). A total score is obtained by summing the responses to the seven items \[range 7 (never) to 35 (always)\] and converting to a standardized T-score. The change from baseline in PROMIS Fatigue SF-7a Total Fatigue Score will be presented. |
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed