Back to resultsA Study of Bomedemstat (MK-3543) in Participants With Polycythemia Vera (MK-3543-004)
Primary Purpose
Polycythemia Vera
Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
bomedemstat
Sponsored by
About this trial
This is an interventional treatment trial for Polycythemia Vera focused on measuring polycythemia vera, bomedemstat
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of Polycythemia Vera per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms
- Bone marrow fibrosis score of Grade 0 or Grade 1
- Patients that have failed at least one standard cytoreductive therapy to lower hematocrit
- Platelet count ≥250 x 10ˆ9/L
- Absolute neutrophil count (ANC) ≥1.5 x 10ˆ9/L
- Life expectancy >36 weeks.
- Must have discontinued prior cytoreductive therapy for 2 weeks (4 weeks for interferon) prior to study drug initiation.
Exclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 3 or greater
- 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
- Evidence of increased risk of bleeding, including known bleeding disorders
- Other hematologic/biochemistry requirements, as per protocol
- Pregnant or lactating females
Sites / Locations
- Hematology Oncology of the North Shore ( Site 0104)Recruiting
- University of Michigan Comprehensive Cancer Center ( Site 0008)Recruiting
- Comprehensive Cancer Centers of Nevada - Peak ( Site 0118)Recruiting
- Duke University Medical Center ( Site 0016)Recruiting
- United Lincolnshire Hospitals NHS Trust ( Site 0204)Recruiting
- Imperial College London ( Site 0025)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
bomedemstat
Arm Description
Participants will receive bomedemstat daily for 36 weeks and may qualify for additional treatment thereafter if deriving clinical benefit.
Outcomes
Primary Outcome Measures
Number of participants with adverse events (AEs)
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 presented.
Number of participants who discontinued study intervention due to AEs
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 presented.
Number of participants with change from baseline of hematocrit to <45% without phlebotomy at 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 a change from baseline of hematocrit to <45% without phlebotomy at Week 36 will be presented.
Secondary Outcome Measures
Duration of reduction of hematocrit to <45% without phlebotomy
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 presented.
Number of participants with platelet count ≤ 450 x 10^9/L at 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 presented.
Duration of platelet count ≤ 450 x 10^9/L in participants at 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 presented.
Number of participants with white blood cell (WBC) count of <10 x 10^9/L at 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 presented.
Duration of white blood cell (WBC) count <10 x 10^9/L in participants at 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 presented.
Number of participants with thrombotic events
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 presented.
Number of participants with major hemorrhagic events
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 presented.
Number of participants with a reduction in splenic volume in patients with an enlarged spleen at baseline
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 presented.
Number of participants with progressive disease (PD)
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 presented.
Maximum plasma concentration (Cmax) of bomedemstat
Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of bomedemstat.
Area under the curve 0-24 (AUC 0-24) of bomedemstat
AUC is defined as area under curve exposure. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC of bomedemstat.
Half life (t½) of bomedemstat
t½ is the time required for 50% of drug to be cleared from serum. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine t½ of bomedemstat.
Number of participants with change from baseline in The Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) 7-day recall at Week 36
The MFSAF v4.0 is a 7-item questionnaire used for the assessment of myelofibrosis symptoms that asks participants to report symptom severity at its worst for each of the seven items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale and has a minimum score of 0 and a maximum score of 70. Participants will be evaluated with the MFSAF v4.0 at designated time points during the study. The number of participants with a change from baseline by Week 36 will be reported.
Number of participants with change from baseline in Patient Global Impression of Change (PGIC)
The PGIC is a one-item questionnaire based on the Clinical Global Impressions (CGI) scale and adapted to the participant. It measures change in clinical status from a scale of 1-7 with 1 being very much improved to 7 being very much worse. The number of participants with a change in PGIC score from Week 12 to Week 36 will be presented.
Number of participants with a durable change in participant-reported symptom burden on the MFSAF v4.0 7-day recall
The MFSAF v4.0 is a 7-item questionnaire used for the assessment of myelofibrosis symptoms that asks participants to report symptom severity at its worst for each of the seven items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale and has a minimum score of 0 and a maximum score of 70. Participants will be evaluated with the MFSAF v4.0 at designated time points during the study. The number of participants achieving a durable change of the MFSAF Score will be presented.
Full Information
NCT ID
NCT05558696
First Posted
September 20, 2022
Last Updated
October 12, 2023
Sponsor
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
1. Study Identification
Unique Protocol Identification Number
NCT05558696
Brief Title
A Study of Bomedemstat (MK-3543) in Participants With Polycythemia Vera (MK-3543-004)
Official Title
A Phase 2 Multi-Center, Open Label Study to Assess the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Bomedemstat in Patients With Polycythemia Vera (PV)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 7, 2023 (Actual)
Primary Completion Date
February 20, 2025 (Anticipated)
Study Completion Date
February 21, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a Phase 2 open label study of an orally administered lysine-specific demethylase 1 (LSD1) inhibitor, bomedemstat, in participants with polycythemia vera. The primary hypothesis is that bomedemstat is a safe and tolerable orally available agent when administered to participants with PV; and inhibition of LSD1 by bomedemstat will induce hematologic response in this population by 36 weeks, improve symptom burden and reduce spleen size in participants with enlarged spleen at baseline.
Detailed Description
This is a Phase 2 multi-center, open-label study evaluating the safety, efficacy, pharmacokinetics and pharmacodynamics of bomedemstat administered orally once daily in participants with PV.
Participants will receive 36 weeks of dosing and may qualify for additional treatment thereafter.
Participants will be followed closely throughout the study for both adverse events by frequent monitoring of clinical signs and symptoms as well as safety labs. Efficacy and pharmacodynamic effects will be closely monitored by frequent hematology assessments of peripheral blood. Throughout dosing, transfusions or phlebotomy may be administered if needed in accordance with standard institutional guidelines.
To ensure safety, a Safety Advisory Board will perform periodic reviews of safety parameters and pharmacodynamic markers.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycythemia Vera
Keywords
polycythemia vera, bomedemstat
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
bomedemstat
Arm Type
Experimental
Arm Description
Participants will receive bomedemstat daily for 36 weeks and may qualify for additional treatment thereafter if deriving clinical benefit.
Intervention Type
Drug
Intervention Name(s)
bomedemstat
Other Intervention Name(s)
MK-3543, IMG-7289
Intervention Description
Oral tablet
Primary Outcome Measure Information:
Title
Number of participants with adverse events (AEs)
Description
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 presented.
Time Frame
Up to ~40 weeks
Title
Number of participants who discontinued study intervention due to AEs
Description
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 presented.
Time Frame
Up to ~36 weeks
Title
Number of participants with change from baseline of hematocrit to <45% without phlebotomy at Week 36
Description
Hematocrit will be analyzed by taking blood samples from participants at designated time points during the study. The number of participants who have a change from baseline of hematocrit to <45% without phlebotomy at Week 36 will be presented.
Time Frame
Baseline through Week 36
Secondary Outcome Measure Information:
Title
Duration of reduction of hematocrit to <45% without phlebotomy
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Number of participants with platelet count ≤ 450 x 10^9/L at Week 36
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Duration of platelet count ≤ 450 x 10^9/L in participants at Week 36
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Number of participants with white blood cell (WBC) count of <10 x 10^9/L at Week 36
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Duration of white blood cell (WBC) count <10 x 10^9/L in participants at Week 36
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Number of participants with thrombotic events
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Number of participants with major hemorrhagic events
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Number of participants with a reduction in splenic volume in patients with an enlarged spleen at baseline
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Number of participants with progressive disease (PD)
Description
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 presented.
Time Frame
Baseline through Week 36
Title
Maximum plasma concentration (Cmax) of bomedemstat
Description
Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of bomedemstat.
Time Frame
At designated time points on Day 1, Day 15 and at investigators choice of one of any regularly scheduled study visit from Week 4 (Day 29) to Week 8 (Day 57)
Title
Area under the curve 0-24 (AUC 0-24) of bomedemstat
Description
AUC is defined as area under curve exposure. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine AUC of bomedemstat.
Time Frame
At designated time points on Day 1, Day 15 and at investigators choice of one of any regularly scheduled study visit from Week 4 (Day 29) to Week 8 (Day 57)
Title
Half life (t½) of bomedemstat
Description
t½ is the time required for 50% of drug to be cleared from serum. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine t½ of bomedemstat.
Time Frame
At designated time points on Day 1, Day 15 and at investigators choice of one of any regularly scheduled study visit from Week 4 (Day 29) to Week 8 (Day 57)
Title
Number of participants with change from baseline in The Myelofibrosis Symptom Assessment Form version 4.0 (MFSAF v4.0) 7-day recall at Week 36
Description
The MFSAF v4.0 is a 7-item questionnaire used for the assessment of myelofibrosis symptoms that asks participants to report symptom severity at its worst for each of the seven items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale and has a minimum score of 0 and a maximum score of 70. Participants will be evaluated with the MFSAF v4.0 at designated time points during the study. The number of participants with a change from baseline by Week 36 will be reported.
Time Frame
Baseline through Week 36
Title
Number of participants with change from baseline in Patient Global Impression of Change (PGIC)
Description
The PGIC is a one-item questionnaire based on the Clinical Global Impressions (CGI) scale and adapted to the participant. It measures change in clinical status from a scale of 1-7 with 1 being very much improved to 7 being very much worse. The number of participants with a change in PGIC score from Week 12 to Week 36 will be presented.
Time Frame
Week 12 through Week 36
Title
Number of participants with a durable change in participant-reported symptom burden on the MFSAF v4.0 7-day recall
Description
The MFSAF v4.0 is a 7-item questionnaire used for the assessment of myelofibrosis symptoms that asks participants to report symptom severity at its worst for each of the seven items on a 0 (Absent) to 10 (Worst Imaginable) numeric rating scale and has a minimum score of 0 and a maximum score of 70. Participants will be evaluated with the MFSAF v4.0 at designated time points during the study. The number of participants achieving a durable change of the MFSAF Score will be presented.
Time Frame
Baseline through Week 36
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Hematology Oncology of the North Shore ( Site 0104)
City
Skokie
State/Province
Illinois
ZIP/Postal Code
60076-1264
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
847-675-3900
Facility Name
University of Michigan Comprehensive Cancer Center ( Site 0008)
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
734-647-1017
Facility Name
Comprehensive Cancer Centers of Nevada - Peak ( Site 0118)
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89128
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
702-952-2140
Facility Name
Duke University Medical Center ( Site 0016)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
919-684-8111
Facility Name
United Lincolnshire Hospitals NHS Trust ( Site 0204)
City
Lincoln
State/Province
Great Britain
ZIP/Postal Code
LN2 5QY
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+441205445790
Facility Name
Imperial College London ( Site 0025)
City
London
State/Province
Great Britain
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
442033134340
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information
Learn more about this trial
A Study of Bomedemstat (MK-3543) in Participants With Polycythemia Vera (MK-3543-004)
We'll reach out to this number within 24 hrs