Bomedemstat vs Hydroxyurea for Essential Thrombocythemia (MK-3543-007)

Essential Thrombocythemia Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind, Active-Comparator-Controlled Clinical Study to Evaluate the Efficacy and Safety of Bomedemstat (MK-3543) Versus Hydroxyurea in Cytoreductive Therapy Naïve Essential Thrombocythemia Participants

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06456346
• Other study ID #: 3543-007
• Secondary ID: 2023-505232-36MK
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 5, 2024
• Est. completion date: May 14, 2029

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of bomedemstat compared with hydroxyurea in cytoreductive therapy naïve essential thrombocythemia (ET) participants for whom cytoreductive therapy is indicated. Its primary objective is to compare bomedemstat to hydroxyurea with respect to durable clinicohematologic response (DCHR). The primary hypothesis is that bomedemstat is superior to hydroxyurea with respect to DCHR.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 300
• Est. completion date: May 14, 2029
• Est. primary completion date: May 14, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of Essential Thrombocythemia (ET) based on World Health Organization Criteria for myeloproliferative neoplasms, and in indication for cytoreductive therapy

• 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 received no prior cytoreductive treatment for their ET

• Human Immunodeficiency Virus (HIV)-infected participants have well controlled HIV on antiretroviral therapy

• 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

Exclusion Criteria:

• History of any illness/impairment of gastrointestinal function that might interfere with drug absorption

• History of a malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years

• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease

• Has an active infection requiring systemic therapy

• Has had a major surgery <4 weeks prior to first dose of study intervention or has not recovered from side effects of major surgery >4 weeks prior to first dose

Related Conditions & MeSH terms

• Essential Thrombocythemia
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Bomedemstat
Oral capsule
• Hydroxyurea
Oral capsule
• Bomedemstat placebo
Oral capsule placebo
• Hydroxyurea placebo
Oral capsule placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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, 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.	Up to Week 52
Secondary	Change From Baseline in Myelofibrosis Symptom Assessment Form version 4.0 (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.	Baseline and pre-specified timepoints up to Week 52
Secondary	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.	Baseline and pre-specified timepoints up to Week 52
Secondary	Change From Baseline in MFSAF v4.0 Total Symptom 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. The change from baseline in MFSAF total score for all symptoms will be presented.	Baseline and Week 52
Secondary	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 Week 52
Secondary	Number of Participants Who Experience 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 approximately 52 weeks
Secondary	Number of Participants Who Experience 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 approximately 52 weeks
Secondary	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 AML as assessed by the adjudication committee.	Up to Week 52
Secondary	Event Free Survival (EFS)	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 Week 52
Secondary	Number of Participants Who Experience One or More Adverse Events (AEs)	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 approximately 52 weeks
Secondary	Number of Participants Who Discontinue Study Intervention 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.	Up to approximately 52 weeks

External Links

•   Merck Clinical Trials Information