Thrombocythemia, Essential, Primary Myelofibrosis
Conditions
Brief summary
This is a multi-center, open-label extension study to assess the long-term safety and efficacy of bomedemstat administered orally once daily in participants with a Myeloproliferative Neoplasm (MPN) who participated in a prior bomedemstat study such as, but not limited to, IMG-7289-CTP-102/MK-3543-002 (NCT03136185) and IMG-7289-CTP-201/MK-3543-003 (NCT04254978) (referred to hereafter as 'feeder studies').
Interventions
DRUGBomedemstat
Capsule (oral)
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Inclusion Criteria include, but are not limited to: * Has completed at least one Treatment Period (TP) in a prior bomedemstat Myeloproliferative Neoplasms (MPN) protocol (such as, but not limited to, IMG-7289-CTP-102/MK-3543-002 (NCT03136185) and IMG-7289-CTP-201/MK-3543-003) (NCT04254978). * In the estimation of the Investigator, the risk-benefit favors continued dosing with bomedemstat.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience an Adverse Event (AE) | Up to ~32 months | An AE is any undesirable physical, psychological or behavioral effect experienced by a participant during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any clinically significant abnormalities in vital signs and lab values, untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat under this protocol until completion of the study. The percentage of participants who experienced an AE is presented. |
| Percentage of Participants Who Discontinue Study Intervention Due to an AE | Up to ~32 months | An AE is any undesirable physical, psychological or behavioral effect experienced by a participant during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any clinically significant abnormalities in vital signs and lab values, untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat under this protocol until completion of the study. The percentage of participants who discontinued study intervention due to an AE is presented. |
| Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF. | Baseline and Days 169, 339, 509, 679, 849 and 924 | Mean Spleen volume reduction (mL) in participants with MF as measured by central laboratory imaging analysis of MRI (or CT where applicable) approximately every 48 weeks. Per protocol only participants with MF were analyzed for this outcome measure. The change in spleen volume from baseline is presented. |
| Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Baseline and Days 29, 57, 85, 113, 141, 169, 198, 226, 254, 282, 310, 338, 367, 395, 423, 451, 479, 507, 536, 564, 592, 620, and 648 | Blood samples were taken at designated time points to determine platelet count. Percentage of participants with ET who achieve a reduction of platelet counts to \<= 400 K/uL (400 x 10\^9/L) in the absence of new thromboembolic events is presented. |
Countries
Australia, Germany, Hong Kong, Italy, New Zealand, United Kingdom, United States
Participant flow
Recruitment details
Participants with Myeloproliferative Neoplasms (MPNs) who participated in a prior bomedemstat study such as, but not limited to, IMG-7289-CTP-102/MK-3543-002 (NCT03136185) and IMG-7289-CTP-201/MK-3543-003 (NCT04254978) (referred to hereafter as 'feeder studies') were included in the recruitment.
Pre-assignment details
Participants were assigned to either the Essential thrombocythemia (ET) arm or Myelofibrosis (MF) arm based on prior diagnosis.
Participants by arm
| Arm | Count |
|---|---|
| Essential Thrombocythemia (ET) Participants with ET received bomedemstat daily as an oral capsule. The daily dose of bomedemstat was titrated for each participant to a dose that reduced platelets to the target range associated with the participant's underlying MPN. | 52 |
| Myelofibrosis (MF) Participants with MF received bomedemstat daily as an oral capsule. The daily dose of bomedemstat was titrated for each participant to a dose that reduced platelets to the target range associated with the participant's underlying MPN. | 29 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Disease Progression | 1 | 2 |
| Overall Study | Physician Decision | 1 | 2 |
| Overall Study | Sponsor decision | 11 | 9 |
| Overall Study | Subject decision | 1 | 0 |
| Overall Study | Transferred to Extension Study MK-3543-017 (NCT06351631) | 29 | 7 |
| Overall Study | Withdrawal by Subject | 1 | 6 |
Baseline characteristics
| Characteristic | Essential Thrombocythemia (ET) | Myelofibrosis (MF) | Total |
|---|---|---|---|
| Age, Continuous | 65.8 Years STANDARD_DEVIATION 11.01 | 65.3 Years STANDARD_DEVIATION 9.68 | 65.6 Years STANDARD_DEVIATION 10.49 |
| Baseline Platelet Counts in thousands per microliter (10^3 cells/μL) | 380.4 10^3 cells/μL STANDARD_DEVIATION 207.44 | 190.5 10^3 cells/μL STANDARD_DEVIATION 209.64 | 312.4 10^3 cells/μL STANDARD_DEVIATION 226.29 |
| Baseline Spleen Volume by Magnetic resonance imaging/computerized tomography (MRI/CT) in mL | — | 835.21 mL | 835.21 mL |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 51 Participants | 28 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 14 Participants | 15 Participants | 29 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 35 Participants | 13 Participants | 48 Participants |
| Sex: Female, Male Female | 29 Participants | 14 Participants | 43 Participants |
| Sex: Female, Male Male | 23 Participants | 15 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 52 | 0 / 29 |
| other Total, other adverse events | 45 / 52 | 28 / 29 |
| serious Total, serious adverse events | 19 / 52 | 12 / 29 |
Outcome results
Primary
Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF.
Mean Spleen volume reduction (mL) in participants with MF as measured by central laboratory imaging analysis of MRI (or CT where applicable) approximately every 48 weeks. Per protocol only participants with MF were analyzed for this outcome measure. The change in spleen volume from baseline is presented.
Time frame: Baseline and Days 169, 339, 509, 679, 849 and 924
Population: The modified intent to treat (mITT) population included all participants who were enrolled in the study, received at least 1 dose of study intervention, and who had a nonmissing baseline and at least 1 nonmissing postbaseline efficacy assessment. Participants were analyzed according to treatment received in the study. Per protocol only participants with MF were analyzed for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Myelofibrosis (MF) | Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF. | Day 169 | -101.570 mL | Standard Deviation 92.6876 |
| Myelofibrosis (MF) | Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF. | Day 339 | -67.645 mL | Standard Deviation 249.0079 |
| Myelofibrosis (MF) | Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF. | Day 509 | -5.920 mL | Standard Deviation 143.1692 |
| Myelofibrosis (MF) | Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF. | Day 679 | -61.000 mL | Standard Deviation 396.252 |
| Myelofibrosis (MF) | Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF. | Day 849 | -38.840 mL | — |
| Myelofibrosis (MF) | Mean Spleen Volume Reduction Based on Spleen Volume Measured by MRI in Participants With MF. | Day 924 | 80.575 mL | Standard Deviation 10.3308 |
Primary
Percentage of Participants Who Discontinue Study Intervention Due to an AE
An AE is any undesirable physical, psychological or behavioral effect experienced by a participant during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any clinically significant abnormalities in vital signs and lab values, untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat under this protocol until completion of the study. The percentage of participants who discontinued study intervention due to an AE is presented.
Time frame: Up to ~32 months
Population: All participants who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Essential Thrombocythemia (ET) | Percentage of Participants Who Discontinue Study Intervention Due to an AE | 15.4 Percentage of Participants |
| Myelofibrosis (MF) | Percentage of Participants Who Discontinue Study Intervention Due to an AE | 10.3 Percentage of Participants |
Primary
Percentage of Participants Who Experience an Adverse Event (AE)
An AE is any undesirable physical, psychological or behavioral effect experienced by a participant during participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. This includes any clinically significant abnormalities in vital signs and lab values, untoward signs or symptoms experienced by the participant from the time of first dose with bomedemstat under this protocol until completion of the study. The percentage of participants who experienced an AE is presented.
Time frame: Up to ~32 months
Population: All participants who received at least one dose of study intervention
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Essential Thrombocythemia (ET) | Percentage of Participants Who Experience an Adverse Event (AE) | 98.1 Percentage of Participants |
| Myelofibrosis (MF) | Percentage of Participants Who Experience an Adverse Event (AE) | 100.0 Percentage of Participants |
Primary
Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events
Blood samples were taken at designated time points to determine platelet count. Percentage of participants with ET who achieve a reduction of platelet counts to \<= 400 K/uL (400 x 10\^9/L) in the absence of new thromboembolic events is presented.
Time frame: Baseline and Days 29, 57, 85, 113, 141, 169, 198, 226, 254, 282, 310, 338, 367, 395, 423, 451, 479, 507, 536, 564, 592, 620, and 648
Population: The modified intent to treat (mITT) population included all participants who were enrolled in the study, received at least 1 dose of study intervention, and who had a nonmissing baseline and at least 1 nonmissing postbaseline efficacy assessment. Per protocol only participants with ET were analyzed for this outcome measure. Participants were analyzed according to treatment received in the study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 29 | 77.1 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 57 | 72.9 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 85 | 72.0 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 113 | 78.4 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 141 | 91.8 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 169 | 89.4 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 198 | 86.7 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 226 | 81.8 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 254 | 79.5 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 282 | 75.0 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 310 | 81.4 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 338 | 83.7 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 367 | 76.2 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 395 | 78.0 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 423 | 80.0 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 451 | 82.1 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 479 | 75.7 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 507 | 96.2 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 536 | 94.7 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 564 | 86.7 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 592 | 72.7 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 620 | 85.7 Percentage of participants |
| Essential Thrombocythemia (ET) | Percentage of Participants With ET Who Achieve a Reduction of Platelet Counts to <= 400 K/uL (400 x 10^9/L) in the Absence of New Thromboembolic Events | Day 648 | 83.3 Percentage of participants |