Bomedemstat vs Hydroxyurea for Essential Thrombocythemia (MK-3543-007)
NCT Number: NCT06456346
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Essential Thrombocythemia
Interventions: DRUG: Bomedemstat|DRUG: Hydroxyurea|DRUG: Bomedemstat placebo|DRUG: Hydroxyurea placebo
Sponsor: Merck Sharp & Dohme LLC
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 300
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-07-16
Completion Date: 2029-05-14
Locations: Royal Adelaide Hospital-Haematology Clinical Trials Unit ( Site 0203), Adelaide, South Australia, 5000, Australia|Hadassah Medical Center ( Site 0424), Jerusalem, 9112001, Israel|Sheba Medical Center ( Site 0428), Ramat Gan, 5265601, Israel|Hokkaido University Hospital ( Site 0601), Sapporo, Hokkaido, 060-8648, Japan|Kobe City Medical Center General Hospital ( Site 0603), Kobe, Hyogo, 650-0047, Japan|Kanazawa University Hospital ( Site 0614), Kanazawa, Ishikawa, 920-8641, Japan|Mie University Hospital ( Site 0615), Tsu, Mie, 514-8507, Japan|Kansai Medical University Hospital ( Site 0607), Hirakata, Osaka, 573-1191, Japan|Kindai University Hospital- Osakasayama Campus-Hematology and Rheumatology ( Site 0600), Osakasayama, Osaka, 589-8511, Japan|Juntendo University Hospital ( Site 0611), Bunkyo-ku, Tokyo, 113-8431, Japan|University of Yamanashi Hospital ( Site 0606), Chuo, Yamanashi, 409-3898, Japan|Fukushima Medical University ( Site 0616), Fukushima, 960-1295, Japan|University of Miyazaki Hospital ( Site 0609), Miyazaki, 889-1692, Japan|Okayama University Hospital ( Site 0604), Okayama, 700-8558, Japan|Nippon Medical School Hospital ( Site 0608), Tokyo, 113-8603, Japan|National Cheng Kung University Hospital-Clinical Trial Center ( Site 0245), Tainan, 704, Taiwan

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.

Primary Outcome Measures: 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 Outcome Measures: 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|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|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|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|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|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|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|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|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|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