A Study of Bomedemstat (IMG-7289/MK-3543) Compared to Best Available Therapy (BAT) in Participants With Essential Thrombocythemia and an Inadequate Response or Intolerance of Hydroxyurea (MK-3543-006)

Phase 3Active Not RecruitingNCT06079879

Merck Sharp & Dohme LLC340 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

340

Conditions

Essential Thrombocythemia

Interventions

BomedemstatDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (163)

Palo Verde Hematology/ Oncology Center, Ltd. ( Site 3496)

Glendale, Arizona, United States

Los Angeles Cancer Network ( Site 3491)

Glendale, California, United States

Stanford Cancer Institute ( Site 0107)

Stanford, California, United States

The Lundquist Institute ( Site 3423)

Torrance, California, United States

University of Colorado Anschutz Medical Campus ( Site 3425)

Aurora, Colorado, United States

Outcomes

Primary Outcomes

Durable Clinicohematologic Response (DCHR) Rate

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.

Time frame: Up to approximately 52 weeks

Secondary Outcomes

Clinicohematologic Response (CHR) Rate

CHR rate is the percentage of participants with CHR, defined as a confirmed reduction of platelet count to ≤400 × 10\^9/L and absence of WBC count elevation to \>10 × 10\^9/L locally assessed to be due to ET, maintained for at least 12 weeks, and the absence of any thrombotic or major hemorrhagic events or disease progression to MF, MDS or AML by Week 52.

Time frame: Up to approximately 52 weeks

Hematologic Response (HR) Rate

HR rate is the percentage of participants with HR, HR is defined as the time from the first confirmed hematologic response to first documented evidence of confirmed platelet increase or confirmed WBC increase after latest confirmed hematologic response date.

Time frame: Up to approximately 52 weeks

Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score

The PROMIS Fatigue SF-7a 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. The total score is used in the analysis and is obtained by summing keyed scores of all items. Scores can range from 7 to 35, with higher scores indicating greater fatigue.

Time frame: Baseline and pre-specified timepoints through Week 52

Change From Baseline in Total Symptom Score as Measured on the MFSAF v4.0

The MFSAF v4.0 is a 7-item participant-reported myelofibrosis symptom assessment which 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.

Time frame: Baseline and pre-specified timepoints through Week 52

Duration of Durable Clinicohematologic Response (DODCHR)

For participants who demonstrate DCHR, DODCHR is defined as the time from the first documented evidence of confirmed reduction of platelet and WBC counts until confirmed increase of platelet and WBC counts to above acceptable threshold, thrombotic or major hemorrhagic events, or disease progression to MF, MDS or AML.

Time frame: Up to approximately 52 weeks

Duration of Clinicohematologic Response (DOCHR)

For participants who demonstrate CHR, DOCHR is defined as the time from the first documented evidence of confirmed reduction of platelet and WBC counts until confirmed increase of platelet and WBC count to above acceptable threshold, thrombotic or major hemorrhagic events, or disease progression to MF, MDS or AML.

Time frame: Up to approximately 52 weeks

Duration of Hematologic Response (DOHR)

For participants who demonstrate HR, DOHR is defined as the time from the first confirmed hematologic response to first documented evidence of confirmed platelet increase or confirmed WBC increase after latest confirmed hematologic response date.

Time frame: Up to approximately 52 weeks

Percentage of Participants with Thrombotic Events

Thrombotic events include but are not limited to new or recurrent acute myocardial infarction, unstable angina, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, thrombotic digital ischemia, or other thrombotic events.

Time frame: Up to approximately 52 weeks

Percentage of Participants with Major Hemorrhagic Events

Major hemorrhagic events include but are not limited to fatal bleeding, and/or symptomatic bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or bleeding causing a decrease in hemoglobin level of 2 g/dL or more, or leading to transfusion of 2 or more units of whole blood or red cells.

Time frame: Up to approximately 52 weeks

Percentage of Participants with Disease Progression to Post-ET MF or MDS/AML

Disease progression rate is the percentage of participants with disease progression, defined as the transformation to post-ET MF, MDS, or AML as assessed by the adjudication committee.

Time frame: Up to approximately 52 weeks

Number of Participants with An Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Time frame: Up to approximately 52 weeks

Number of Participants Discontinuing From Study Therapy Due to an AE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

Time frame: Up to approximately 52 weeks