Essential Thrombocythemia
Conditions
Keywords
essential thrombocythemia, ET, bomedemstat, IMG-7289
Brief 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.
Interventions
DRUGBomedemstat
Oral capsule
DRUGHydroxyurea
Oral capsule
DRUGBomedemstat placebo
Oral capsule placebo
DRUGHydroxyurea placebo
Oral capsule placebo
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Essential Thrombocythemia (ET) based on World Health Organization Criteria for myeloproliferative neoplasms, and an indication for cytoreductive therapy regardless of age or risk status * 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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable Clinicohematologic Response (DCHR) Rate | Up to Week 52 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) Individual Fatigue Symptom Item Score | Baseline and pre-specified timepoints up to Week 52 | 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. |
| Change From Baseline in Patient-reported Outcomes Measurement Information System (PROMIS) Fatigue SF-7a Total Fatigue Score | Baseline and pre-specified timepoints up to Week 52 | 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 MFSAF v4.0 Total Symptom Score | Baseline and Week 52 | 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. |
| Duration of Hematologic Remission (DOHR) | Up to Week 52 | 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. |
| Number of Participants Who Experience Thrombotic Events | Up to approximately 52 weeks | 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. |
| Number of Participants Who Experience Major Hemorrhagic Events | Up to approximately 52 weeks | 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. |
| Disease Progression Rate | Up to Week 52 | 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. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 52 weeks | 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. |
| Number of Participants Who Discontinue Study Intervention Due to an AE | Up to approximately 52 weeks | 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. |
Countries
Argentina, Australia, Austria, Canada, Chile, China, Colombia, Denmark, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Mexico, Poland, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed