A Clinical Trial of Bomedemstat in Participants With Polycythemia Vera (MK-3543-025)

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.

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.

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.

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.

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.

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.

For participants who show confirmed hematologic remission, DOHR is defined as the time from the first hematologic remission until loss of hematologic remission.

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 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.

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.

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.

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

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.