Essential Thrombocythemia
Conditions
Brief summary
This is a Phase 2b open label study of an orally administered LSD1 inhibitor, Bomedemstat (MK-3543, formerly called IMG-7289), in patients with essential thrombocythemia. This study investigates the following: * The safety and tolerability of Bomedemstat * The pharmacodynamic effect of Bomedemstat
Detailed description
This is a Phase 2 multi-center, open-label study evaluating the safety, efficacy and pharmacodynamics of Bomedemstat administered orally once daily in patients with essential thrombocythemia (ET). Patients will be dosed with Bomedemstat for 169 consecutive days in the Initial Treatment Period (ITP). Qualifying patients may continue to receive Bomedemstat in the Additional Treatment Period (ATP). Safety will be evaluated by clinical assessments of safety parameters i.e., safety laboratory testing, adverse event reporting, physical examination and vital sign assessments. Pharmacodynamics will be evaluated by hematology assessment, patient reported symptom burden, change in spleen size by palpation and other measures. To ensure safety, a Safety Advisory Board will perform periodic reviews of safety parameters and pharmacodynamic markers.
Interventions
DRUGBomedemstat
Oral administration
Sponsors
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Multi-center, open-label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of Essential Thrombocythemia per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms. * Requires treatment in order to lower platelet count based on patient age over 60 or history of thrombosis. * Have failed at least one standard therapy * Must have discontinued ET therapy at least 1 week (4 weeks for interferon) prior to study drug initiation.
Exclusion criteria
* Has undergone major surgery ≤4 weeks prior to starting study drug or has not recovered from side effects of such surgery. * Unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1). * Uncontrolled active infection. * Current use of prohibited medications * Known HIV infection or active Hepatitis B or Hepatitis C virus infection * Other hematologic/biochemistry requirements, as per protocol * Use of investigational agent within last 14 days * Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 30 months | An AE is any undesirable physical, psychological or behavioral effect experienced by a participant during the study, in conjunction with the use of the drug or biologic, whether or not product related. This includes any untoward signs or symptoms experienced by the participant from the time of first dose with study treatment until completion of the study. The number of participants who experienced an AE is reported. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 28 months | An AE is any undesirable physical, psychological or behavioral effect experienced by a patient during participation in the study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any untoward signs or symptoms experienced by the patient from the time of first dose with study treatment until completion of the study. The number of participants who discontinued study treatment due to an AE is reported. |
| Percentage of Participants With Platelet Count ≤400 k/μL at Day 169 | Up to day 169 | Blood samples were collected at pre-specified timepoints to determine platelet counts. The percentage of participants who achieved reduction in platelet count to ≤400k/μL in the absence of new thrombolytic events is reported. |
Countries
Australia, Germany, Hong Kong, Italy, New Zealand, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bomedemstat Bomedemstat administered daily for 169 consecutive days | 73 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Additional Treatment Period (ATP) | Adverse Event | 7 |
| Additional Treatment Period (ATP) | Physician Decision | 1 |
| Additional Treatment Period (ATP) | Withdrawal by Subject | 3 |
| Initial Treatment Period (ITP) | Adverse Event | 5 |
| Initial Treatment Period (ITP) | Lack of Efficacy | 1 |
| Initial Treatment Period (ITP) | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Bomedemstat |
|---|---|
| Age, Continuous | 64.8 Years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized Aboriginal | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Unknown or not reported | 0 Participants |
| Race/Ethnicity, Customized White | 51 Participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 73 |
| other Total, other adverse events | 72 / 73 |
| serious Total, serious adverse events | 27 / 73 |
Outcome results
Primary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any undesirable physical, psychological or behavioral effect experienced by a patient during participation in the study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any untoward signs or symptoms experienced by the patient from the time of first dose with study treatment until completion of the study. The number of participants who discontinued study treatment due to an AE is reported.
Time frame: Up to approximately 28 months
Population: All participants who were enrolled in the study and received at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bomedemstat | Number of Participants Who Discontinued Study Treatment Due to an AE | 11 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is any undesirable physical, psychological or behavioral effect experienced by a participant during the study, in conjunction with the use of the drug or biologic, whether or not product related. This includes any untoward signs or symptoms experienced by the participant from the time of first dose with study treatment until completion of the study. The number of participants who experienced an AE is reported.
Time frame: Up to approximately 30 months
Population: All participants who were enrolled in the study and received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bomedemstat | Number of Participants Who Experienced an Adverse Event (AE) | 73 Participants |
Primary
Percentage of Participants With Platelet Count ≤400 k/μL at Day 169
Blood samples were collected at pre-specified timepoints to determine platelet counts. The percentage of participants who achieved reduction in platelet count to ≤400k/μL in the absence of new thrombolytic events is reported.
Time frame: Up to day 169
Population: All participants who were enrolled in the study, received at least one dose of study drug, and had a non-missing baseline and at least 1 non-missing post-baseline efficacy assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bomedemstat | Percentage of Participants With Platelet Count ≤400 k/μL at Day 169 | 76.6 Percentage of Participants |
Comparison: Comparison of the true response rate of bomedemstat to a fixed efficacy target of 5%: Null hypothesis (H0): p ≤ 0.05 versus alternate hypothesis (H1): p \> 0.05p-value: <0.0001Exact binomial distribution