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 patient reported outcome measures were designated as exploratory.
Interventions
DRUGBomedemstat
Oral tablet
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 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 |
|---|---|---|
| Number of participants with adverse events (AEs) | Up to ~56 weeks | An AE is 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 will be reported. |
| Number of participants who discontinued study intervention due to AEs | Up to ~52 weeks | An AE is 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 discontinue study intervention due to AEs will be reported. |
| Number of participants with sustained change from baseline of hematocrit to <45% without concomitant phlebotomy at Week 36 | Baseline through Week 36 | Hematocrit will be analyzed by taking blood samples from participants at designated time points during the study. The number of participants who have achieved a sustained change from baseline of hematocrit to \<45% without concomitant phlebotomy at Week 36 will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with white blood cell (WBC) count of <10 x 10^9/L at Week 36 | Baseline through Week 36 | WBC count will be analyzed by taking blood samples from participants at designated time points during the study. The percentage of participants who have a WBC count of \<10 X 10\^9/L will be reported. |
| Duration of white blood cell (WBC) count <10 x 10^9/L in participants at Week 36 | Baseline through Week 36 | WBC count will be analyzed by taking blood samples from participants at designated time points during the study. The duration of the reduction of WBC count \<10 X 10\^9/L in participants will be reported. |
| Number of participants with thrombotic events | Baseline through Week 36 | 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 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. The number of participants with thrombotic events will be reported. |
| Duration of reduction of hematocrit to <45% without phlebotomy | Baseline through Week 36 | Hematocrit will be analyzed by taking blood samples from participants at designated time points during the study. The duration of a reduction in hematocrit to \<45% without phlebotomy up to Week 36 will be reported. |
| Number of participants with a reduction in splenic volume in patients with an enlarged spleen at baseline | Baseline through Week 36 | Spleen volume will be 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. The number of participants with a reduction in spleen volume by Week 36 will be reported. |
| Number of participants with progressive disease (PD) | Baseline through Week 36 | PD is defined as the worsening of PV to post-polycythemia vera myelofibrosis, myelodysplastic syndrome or transformation to acute myeloid leukemia. The number of participants with PD will be reported. |
| Number of participants with major hemorrhagic events | Baseline through Week 36 | Hemorrhagic events are 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. The number of participants with hemorrhagic events will be reported. |
| Number of participants with platelet count ≤ 450 x 10^9/L at Week 36 | Baseline through Week 36 | Platelet count will be analyzed by taking blood samples from participants at designated time points during the study. The percentage of participants who have a platelet count ≤450 X 10\^9/L will be reported. |
| Duration of platelet count ≤ 450 x 10^9/L in participants at Week 36 | Baseline through Week 36 | Platelet count will be analyzed by taking blood samples from participants at designated time points during the study. The duration of the reduction of platelet count of ≤450 X 10\^9/L in participants will be reported. |
Countries
Australia, United Kingdom, United States
Outcome results
None listed