A Study of Bomedemstat (MK-3543) in Participants With Polycythemia Vera (MK-3543-004)

Polycythemia Vera Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05558696
• Other study ID #: 3543-004
• Secondary ID: MK-3543-004IMG-7
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 7, 2023
• Est. completion date: March 24, 2025

Study information

• Verified date: April 2024
• Source: Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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. With Amendment 3, after all ongoing patients have reached 52 weeks of treatment, eligible patients may transition to a bomedemstat extension study if available.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: March 24, 2025
• Est. primary completion date: March 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Polycythemia
• Polycythemia Vera

Intervention

Drug:
• bomedemstat
Oral tablet

Locations

Country	Name	City	State
Australia	Monash Medical Centre ( Site 0006)	Clayton	Victoria
Australia	Royal Perth Hospital ( Site 0504)	Perth	Western Australia
United Kingdom	Boston Pilgrim Hospital ( Site 0207)	Boston	Lincolnshire
United Kingdom	Gloucestershire Royal Hospital ( Site 0205)	Gloucester	England
United Kingdom	United Lincolnshire Hospitals NHS Trust ( Site 0204)	Lincoln	Great Britain
United Kingdom	Guys and St Thomas NHS Foundation Trust - Guys Hospital ( Site 0020)	London	London, City Of
United Kingdom	Imperial College London ( Site 0025)	London	Great Britain
United Kingdom	Royal Gwent Hospital ( Site 0201)	Newport	Wales
United States	University of Michigan Comprehensive Cancer Center ( Site 0008)	Ann Arbor	Michigan
United States	Ohio State University Comprehensive Cancer Center ( Site 0103)	Columbus	Ohio
United States	Duke University Medical Center ( Site 0016)	Durham	North Carolina
United States	Comprehensive Cancer Centers of Nevada - Peak ( Site 0118)	Las Vegas	Nevada
United States	BRCR Global ( Site 0120)	Plantation	Florida
United States	OHSU Knight Cardiovascular Institute Cardiology Clinic - South Waterfront ( Site 0102)	Portland	Oregon
United States	Huntsman Cancer Hospital at the University of Utah ( Site 0119)	Salt Lake City	Utah
United States	Hematology Oncology of the North Shore ( Site 0104)	Skokie	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

Countries where clinical trial is conducted

United States,  Australia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to ~40 weeks
Primary	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.	Up to ~36 weeks
Primary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	Baseline through Week 36
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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.	Baseline through Week 36
Secondary	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.	Week 12 through Week 36
Secondary	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.	Baseline through Week 36

External Links

•   Merck Clinical Trials Information