Bomedemstat for Essential Thrombocythemia

Recruiting at 165 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must not be taking: LSDi, MAOi

Disqualifiers: Malignancy, HIV, GI impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study evaluating the safety and efficacy of bomedemstat (MK-3543) compared with the best available therapy (BAT) in participants with essential thrombocythemia (ET) who have an inadequate response to or are intolerant of hydroxyurea. The primary study hypothesis is that bomedemstat is superior to the best available therapy with respect to durable clinicohematologic response (DCHR).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants may have received up to 3 prior ET-directed cytoreductive agents, which suggests that some medications might be continued. It's best to discuss this with the trial coordinators.

Is Bomedemstat safe for humans?

Bomedemstat, also known as IMG-7289, is part of a class of drugs called LSD1 inhibitors, which have been tested in clinical trials for various conditions, including cancer. While specific safety data for Bomedemstat in essential thrombocythemia is not provided, LSD1 inhibitors have been studied for their safety in humans, and some have shown low hematological side effects (related to blood). ^{1 2 3 4 5}

How is the drug Bomedemstat different from other treatments for essential thrombocythemia?

Bomedemstat is unique because it targets LSD1 (lysine-specific demethylase 1), an enzyme involved in cell cycle regulation and differentiation, which is not a common target for existing treatments of essential thrombocythemia. This makes it a novel approach compared to traditional therapies that may not focus on this specific mechanism. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharpe & Dohme LLC

Eligibility Criteria

This trial is for individuals with essential thrombocythemia who haven't responded well to or can't tolerate hydroxyurea. They should have a life expectancy over one year, agree to contraception if they can father children, and not be pregnant or breastfeeding if female. A bone marrow fibrosis score of Grade 0 or 1 is required, along with certain blood cell count levels.

Inclusion Criteria

My last hormone therapy didn’t work, needing a new treatment.

I have been diagnosed with essential thrombocythemia according to WHO standards.

My bone marrow fibrosis is low grade.

Exclusion Criteria

I am allergic to certain drugs related to my treatment options.

Evidence at the time of Screening of increased risk of bleeding

I am HIV positive with a history of Kaposi's sarcoma or Castleman's Disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either bomedemstat or best available therapy for up to 52 weeks

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extended Treatment

Participants may continue treatment with bomedemstat for up to 152 weeks if they stop responding to BAT

152 weeks

Treatment Details

Interventions

• Bomedemstat

Trial Overview The study tests bomedemstat against the best available treatments like Busulfan and Ruxolitinib in patients with essential thrombocythemia. It aims to see if bomedemstat leads to better long-term control of blood cell counts compared to other options.

Participant Groups

Group I: Bomedemstat Experimental Treatment 1 Intervention

Participants will begin treatment at a dose of 50 mg of bomedemstat daily. Dosage will be adjusted either up or down within specified time parameters for each participant to the dose that provides sufficient exposure to safely inhibit thrombopoiesis to decrease platelet counts to the target range. All participants will be treated daily for up to 52 weeks, and are eligible for an extended treatment phase up to 152 weeks.

Group II: Best Available Therapy Active Control 4 Interventions

Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa, or ruxolitinib as determined by investigator. All participants will be treated per respective approved product labels for up to 52 weeks. Participants receiving BAT for 52 weeks who stop responding to BAT are eligible to switch to bomedemstat and receive this for up to 152 weeks at the investigators discretion.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

Iadademstat, a selective LSD1 inhibitor, was found to be safe and well-tolerated in a phase I trial involving 27 patients with relapsed/refractory acute myeloid leukemia (R/R AML), with a recommended dose of 140 µg/m2/d established for further treatment.

The treatment showed promising signs of efficacy, including reductions in blood and bone marrow blast percentages and one complete remission, particularly in patients with MLL/KMT2A-rearranged AML, indicating its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia. Salamero, O., Montesinos, P., Willekens, C., et al.[2021]

SP-2577 (Seclidemstat), an inhibitor of the KDM1A enzyme, showed statistically significant growth inhibition in some pediatric sarcoma xenografts, particularly in the RMS Rh10 model, but overall had limited activity across the tested models.

Despite some inhibition of tumor growth, SP-2577 did not lead to tumor regressions or consistent changes in key histone modifications or tumor characteristics, indicating that its efficacy may be modest at the evaluated dose and schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC). Kurmasheva, RT., Erickson, SW., Han, R., et al.[2023]

Nine LSD1 inhibitors have progressed to clinical trials for treating hematologic malignancies, showing promise as either standalone or combination therapies.

Innovative design strategies, such as the unique binding mode of quinazoline derivatives, are paving the way for the development of reversible LSD1 inhibitors, which may help minimize side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances of LSD1/KDM1A inhibitors for disease therapy. Zhang, C., Wang, Z., Shi, Y., et al.[2023]

Lysine-specific demethylase 1 (LSD1) is crucial for regulating cell differentiation and proliferation, and various inhibitors have been developed to target its activity in cancer treatment.

Among the LSD1 inhibitors studied, iadademstat (ORY-1001) was found to be the most potent, while many commonly used tool compounds showed low activity and selectivity, indicating that results from these compounds should be interpreted cautiously.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology. Sacilotto, N., Dessanti, P., Lufino, MMP., et al.[2022]

A new series of derivatives of the LSD1 inhibitor S2157 were developed to improve safety and efficacy, particularly by reducing hERG channel inhibition and enhancing microsomal stability.

The most promising derivative, S1427, demonstrated strong LSD1 inhibitory activity while maintaining favorable safety profiles, making it a potential candidate for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and Synthesis of Tranylcypromine-Derived LSD1 Inhibitors with Improved hERG and Microsomal Stability Profiles. Koda, Y., Sato, S., Yamamoto, H., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC). [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Recent advances of LSD1/KDM1A inhibitors for disease therapy. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Comprehensive in Vitro Characterization of the LSD1 Small Molecule Inhibitor Class in Oncology. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Design and Synthesis of Tranylcypromine-Derived LSD1 Inhibitors with Improved hERG and Microsomal Stability Profiles. [2023]