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)

A Phase 3, Randomized, Open-label, Active-Comparator-Controlled Clinical Study to Evaluate the Safety and Efficacy of Bomedemstat (MK-3543/IMG-7289) Versus Best Available Therapy (BAT) in Participants With Essential Thrombocythemia Who Have an Inadequate Response to or Are Intolerant of Hydroxyurea

This is a study evaluating the safety and efficacy of bomedemstat (MK-3543) compared with the best available treatment (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 treatment with respect to durable clinicohematologic response (DCHR).

Study Overview

• Status: Recruiting
• Conditions: Essential Thrombocythemia
• Intervention / Treatment: Drug: Bomedemstat; Drug: Anagrelide; Drug: Busulfan; Drug: Interferon alfa/pegylated interferon alfa; Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Royal Prince Alfred Hospital ( Site 1100)
      • Contact: Study Coordinator; Phone Number: +6195158031
    • St Leonards, New South Wales, Australia, 2065
      • Recruiting
      • Royal North Shore Hospital ( Site 0003)
      • Contact: Study Coordinator; Phone Number: 02 99264171
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 0001)
      • Contact: Study Coordinator; Phone Number: 61870744133
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health-Haematology Research ( Site 0006)
      • Contact: Study Coordinator; Phone Number: +61422611678
    • Melbourne, Victoria, Australia, 3021
      • Recruiting
      • Western Health-Sunshine & Footscray Hospitals-Cancer Services-Cancer Research ( Site 0502)
      • Contact: Study Coordinator; Phone Number: 0407887699
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Recruiting
      • Royal Perth Hospital-Haematology ( Site 0504)
      • Contact: Study Coordinator; Phone Number: +61 8 9224 2405
• Hong Kong
  • Hksar, Hong Kong
    • Recruiting
    • Queen Mary Hospital ( Site 1901)
    • Contact: Study Coordinator; Phone Number: 852 22554542
• Israel
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center ( Site 0904)
    • Contact: Study Coordinator; Phone Number: +972504048732
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center ( Site 2101)
    • Contact: Study Coordinator; Phone Number: 972526669167
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Sourasky Medical Center ( Site 0902)
    • Contact: Study Coordinator; Phone Number: 972524266648
  • Zerifin, Israel, 70300
    • Recruiting
    • Yitzhak Shamir Medical Center ( Site 0901)
    • Contact: Study Coordinator; Phone Number: 97289542443
• Japan
  • Miyazaki, Japan, 889-1692
    • Recruiting
    • University of Miyazaki Hospital ( Site 3609)
    • Contact: Study Coordinator; Phone Number: +81-985-85-1510
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8603
      • Recruiting
      • Nippon Medical School Hospital ( Site 3608)
      • Contact: Study Coordinator; Phone Number: +81-3-3822-2131
  • Yamanashi
    • Chuo, Yamanashi, Japan, 409-3898
      • Recruiting
      • University of Yamanashi Hospital ( Site 3606)
      • Contact: Study Coordinator; Phone Number: +81-55-273-1111
• Korea, Republic of
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 0606)
    • Contact: Study Coordinator; Phone Number: 82222586058
  • Kyonggi-do
    • Seongnam, Kyonggi-do, Korea, Republic of, 13620
      • Recruiting
      • Seoul National University Bundang Hospital-Hematology ( Site 0605)
      • Contact: Study Coordinator; Phone Number: +82-31-010-787-7038
• New Zealand
  • Auckland, New Zealand, 2025
    • Recruiting
    • Aotearoa Clinical Trials ( Site 0050)
    • Contact: Study Coordinator; Phone Number: +6492760044
  • Auckland, New Zealand, 0622
    • Recruiting
    • North Shore Hospital-Department of Haematology ( Site 0051)
    • Contact: Study Coordinator; Phone Number: 64948689207108
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre ( Site 2806)
    • Contact: Study Coordinator; Phone Number: 913908000
  • Valencia, Spain, 46017
    • Recruiting
    • Hospital Universitario Doctor Peset ( Site 0411)
    • Contact: Study Coordinator; Phone Number: +34963189168
• Taiwan
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital-Clinical Trial Center ( Site 3105)
    • Contact: Study Coordinator; Phone Number: +88662353535
  • Taipei, Taiwan, 10048
    • Recruiting
    • National Taiwan University Hospital ( Site 3101)
    • Contact: Study Coordinator; Phone Number: +886223123456
• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Hospital ( Site 3413)
      • Contact: Study Coordinator; Phone Number: 313-717-5706

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 × 109/L (450k /μL) assessed up to 72 hours before first dose of study intervention
• Has an absolute neutrophil count (ANC) ≥0.75 × 109/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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bomedemstat; 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.	Drug: Bomedemstat; Oral Capsule; Other Names: IMG-7289; MK-3543
Active Comparator: Best Available Therapy; 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.	Drug: Anagrelide; Oral Capsule; Drug: Busulfan; Oral Capsule or Oral Tablet; Drug: Interferon alfa/pegylated interferon alfa; Subcutaneous Solution; Drug: Ruxolitinib; Oral Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Durable Clinicohematologic Response (DCHR) Rate	DCHR rate is the percentage of participants with DCHR, defined as a confirmed reduction of platelet count to ≤400 × 109/L, absence of white blood cell (WBC) count elevation to >10 × 109/L locally assessed to be due to ET, 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.	Up to approximately 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Myelofibrosis Symptom Assessment Form (MFSAF) v4.0 Individual Fatigue Symptom Item Score	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. For this outcome measure, the change from baseline through Week 156 in scores for the individual item of fatigue severity will be presented.	Baseline and pre-specified timepoints through Week 156
Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score	The PROMIS F 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. Change from baseline in PROMIS Fatigue SF-7a through Week 156 will be presented.	Baseline and pre-specified timepoints through Week 156
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. MFSAF total score for all symptoms at baseline through Week 156 will be presented.	Baseline and pre-specified timepoints through Week 156
Duration of Clinicohematologic Response (DOCHR)	For participants who demonstrate DCHR, duration of clinicohematologic response is defined as the time from the first documented evidence of confirmed reduction of platelet and WBC count 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.	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.	Up to 156 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.	Up to 156 weeks
Disease Progression Rate	Disease progression rate is the percentage of participants with disease progression, defined as the transformation to post-essential thrombocythemia myelofibrosis, myelodysplastic syndrome, or acute myeloid leukemia as assessed by the adjudication committee. The disease progression rate of participants in each arm will be presented.	Up to approximately 52 weeks
Event Free Survival (EFS)	Event free survival (EFS) is defined as the time from randomization to the first documented thrombotic or major hemorrhagic event or disease progression as assessed by the adjudication committee, or death due to any cause, whichever occurs first.	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.	Up to 180 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. The number of participants who discontinue study treatment due to an adverse event will be presented.	Up to 152 weeks
Duration of Hematologic Remission (DOHR)	For participants who demonstrate hematologic remission, DOHR is defined as the time from the first documented evidence of platelet and WBC counts reduction until platelet or WBC counts increase to above acceptable threshold.	Up to approximately 52 weeks

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharpe & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2023
• Primary Completion (Estimated): August 18, 2026
• Study Completion (Estimated): August 18, 2028

Study Registration Dates

• First Submitted: October 6, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: essential thrombocythemia; ET; IMG-7289; bomedemstat
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombocytosis; Thrombocythemia, Essential; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Interferons; Interferon-alpha; Busulfan; Anagrelide
• Other Study ID Numbers: 3543-006; 2023-504865-21 (Other Identifier: EU CT); IMG-7289-CTP-301 (Other Identifier: Imagobio); MK-3543-006 (Other Identifier: Merck); jRCT2031230658 (Registry Identifier: Japan Registry of Clinical Trials (jRCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No