Polycythemia Vera
Conditions
Keywords
polycythemia vera, bomedemstat
Brief summary
This study will evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics of the orally administered lysine-specific demethylase 1 (LSD1) inhibitor bomedemstat, in participants with polycythemia vera (PV). At Week 36 of dosing, participants will be assessed for eligibility to receive additional treatment through Week 52. Participants deriving clinical benefit and safely tolerating bomedemstat will qualify for continued treatment at the Investigator's discretion.
Detailed description
With Amendment 3, after all ongoing participants have reached 52 weeks of treatment, eligible participants may transition to a bomedemstat extension study if available. With Amendment 4, all secondary PK and participant reported outcome measures were designated as exploratory. Per protocol, participants who derived clinical benefit (no progressive disease) and safely tolerated drug may have qualified for enrollment into the bomedemstat extension study (NCT06351631).
Interventions
DRUGBomedemstat
Oral capsule
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
* Has a diagnosis of Polycythemia Vera per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms * Has a bone marrow fibrosis score of Grade 0 or Grade 1 * Has failed at least one standard cytoreductive therapy to lower hematocrit * Has a life expectancy \>36 weeks * Has discontinued prior cytoreductive therapy for 2 weeks (4 weeks for interferon) prior to study drug initiation
Exclusion criteria
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or greater * Has unresolved treatment related toxicities from prior therapies (unless resolved to ≤ Grade 1) * Has an uncontrolled active infection * Has a known human immunodeficiency virus (HIV) infection or active Hepatitis A, Hepatitis B or Hepatitis C virus infection * Has evidence of increased risk of bleeding, including known bleeding disorders * Is pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained 12-week Reduction of Hematocrit (Hct) to <45% Without Concomitant Phlebotomy by Week 36 | Up to approximately 36 weeks | Hematocrit (Hct) was analyzed by taking blood samples from participants at designated time points during the study. Participants were considered responders if they achieved a sustained reduction of Hct to \<45% for 12 weeks (84 calendar days) by Week 36 AND there was no concomitant phlebotomy performed during the sustained reduction. Baseline data was defined as the data most recently collected prior to the first dose. A Clopper-Pearson (exact binomial) two-sided 95% confidence interval for the percentage of responders was presented. The percentage of participants who achieved a sustained 12-week reduction of Hct to \<45% without concomitant phlebotomy at Week 36 are reported. |
| Number of Participants With Adverse Events (AEs) | Up to approximately 52 weeks | An AE was defined as 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. The number of participants with one or more AEs are reported. |
| Number of Participants Who Discontinued Study Intervention Due to AEs | Up to approximately 52 weeks | An AE was defined as 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. The number of participants who discontinued study intervention due to an AE are reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Platelet Count ≤ 450 x 10^9/L | Up to approximately 22 months | Total response duration was defined as the summation of all platelet ≤450 x 10\^9/L response durations, where an individual response duration starts at the timepoint where platelet count ≤450 x 10\^9/L and ends at the first subsequent occurrence of platelet \>450 x 10\^9/L. Platelet counts were analyzed by taking blood samples from participants at designated time points during the study. The duration of platelet count ≤450 X 10\^9/L in participants are reported. |
| Percentage of Participants With White Blood Cell (WBC) Count <10 x 10^9/L by Week 36 | Up to approximately 36 weeks | WBC count was analyzed by taking blood samples from participants at designated time points during the study. Participants who enter the study with WBC counts \<10 X 10\^9/L must achieve an additional on-study WBC count \<10 X 10\^9/L to be considered responders. A Clopper-Pearson (exact binomial) two-sided 95% confidence interval for the percentage of responders is presented. Baseline data was defined as the data most recently collected prior to the first dose. The percentage of participants who have a WBC count \<10 X 10\^9/L week 36 are reported. |
| Duration of White Blood Cell (WBC) Count <10 x 10^9/L | Up to approximately 22 months | Total response duration was defined as the summation of all WBC \<10 x 10\^9/L response durations, where an individual response duration starts at the timepoint when WBC \<10 x 10\^9/L and ends at the first subsequent occurrence of WBC ≥ 10 x 10\^9/L. WBC count was analyzed by taking blood samples from participants at designated time points during the study. The duration of WBC count \<10 X 10\^9/L in participants are reported. |
| Number of Participants With Major Hemorrhagic Events | Up to approximately 22 months | Hemorrhagic events were defined as: Major Bleeding (MB) Events such as 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 fall in hemoglobin level of 2 g/dL or more, or leading to transfusion of 2 or more units of whole blood or red cells; Clinically Relevant Non-Major Bleeding (CRNMB) Events Leading to hospitalization or increased level of care or clinically important, prompting a face-to-face medical evaluation. Baseline data was defined as the data most recently collected prior to the first dose. The number of participants with major hemorrhagic events are reported. |
| Number of Participants With an Enlarged Spleen at Baseline Who Had a Reduction in Splenic Volume by 36 Weeks | Up to approximately 36 weeks | Spleen volume was measured by magnetic resonance imaging (MRI) (or computerized tomography \[CT\] if participant is not a candidate for MRI) of the abdomen according to standard procedures. Baseline data was defined as the data most recently collected prior to the first dose. The number of participants with an enlarged spleen at baseline (volume \>450 cm\^3) who achieved any reduction in spleen volume by Week 36 are reported. |
| Number of Participants With Thrombotic Events | Up to approximately 22 months | Thrombotic events are defined as: new or recurrent acute myocardial infarction; unstable angina; stroke; transient ischemic attack (TIA); deep venous thrombosis (DVT); pulmonary embolism (PE); thrombotic digital ischemia; other thrombotic events such as peripheral limb ischemia or Budd-Chiari syndrome that are assessed to be due to underlying polycythemia vera (PV); other vascular occlusive events such as symptoms of cardiac, abdominal or peripheral limb ischemia supported by objective evidence of vessel disease and/or ischemia. Baseline data was defined as the data most recently collected prior to the first dose. The number of participants with thrombotic events are reported. |
| Number of Participants With Progressive Disease (PD) | Up to approximately 52 weeks | PD was defined as the worsening of Polycythemia Vera (PV) to post-PV myelofibrosis, myelodysplastic syndrome or transformation to acute myeloid leukemia. Baseline data was defined as the data most recently collected prior to the first dose. The number of participants with PD are reported. |
| Duration of Reduction of Hematocrit (Hct) to <45% Without Phlebotomy | Up to approximately 22 months | Total response duration was defined as the summation of all Hct \<45% response durations, where an individual response duration starts at the timepoint where the Hct \<45% and ends at the first subsequent occurrence of phlebotomy or Hct \>=45%. Hct was analyzed by taking blood samples from participants at designated time points during the study. Duration of reduction of Hct to \<45% without phlebotomy was presented. |
| Percentage of Participants With Platelet Count ≤ 450 x 10^9/L by Week 36 | Up to approximately 36 weeks | Platelet count was analyzed by taking blood samples from participants at designated time points during the study. Participants who enter the study with platelet counts ≤450 X 10\^9/L must achieve an additional on-study platelet count ≤450 X 10\^9/L to be considered responders. A Clopper-Pearson (exact binomial) two-sided 95% confidence interval for the percentage of responders is presented. Baseline data was defined as the data most recently collected prior to the first dose. The percentage of participants who have a platelet count ≤450 X 10\^9/L by week 36 are reported. |
Countries
Australia, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
This study recruited participants with Polycythemia Vera (PV) requiring cytoreduction that have failed at least one standard cytoreductive therapy (failure is the equivalent of resistance or intolerance).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65.0 Years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mean Hematocrit Counts at Baseline | 43.99 Percentage STANDARD_DEVIATION 4.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 20 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 8 / 20 |
Outcome results
None listed