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)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 3

Conditions: Essential Thrombocythemia

Treatments: Drug: Interferon alfa/pegylated interferon alfa; Drug: Busulfan; Drug: Ruxolitinib; Drug: Bomedemstat; Drug: Anagrelide

Study type: Interventional

Funder types: Industry

Identifiers

NCT06079879

IMG-7289-CTP-301 (Other Identifier)

3543-006

MK-3543-006 (Other Identifier)

jRCT2031230658 (Registry Identifier)

2023-504865-21 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has a diagnosis of ET per WHO 2016 diagnostic criteria for myeloproliferative neoplasms
• Has a 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: hydroxyurea resistance (or inadequate response) or hydroxyurea 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 lines of therapy 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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300 participants in 2 patient groups

Bomedemstat

Experimental group

Description:

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 152 weeks.

Treatment:

Drug: Bomedemstat

Best Available Therapy

Active Comparator group

Description:

Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa, 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 152 weeks at the investigators discretion.

Treatment:

Drug: Anagrelide

Drug: Ruxolitinib

Drug: Busulfan

Drug: Interferon alfa/pegylated interferon alfa