Bomedemstat for Blood Disorders

Recruiting at 15 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Bomedemstat

Disqualifiers: Other study, Noncompliance, 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

400 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary purpose of the study is to transition participants into an extension study to collect long-term safety and efficacy data. The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have shown the following criteria: * Participants from the IMG-7289-202/MK-3543-005 (NCT05223920) study must have received at least 6 months of treatment with bomedemstat; * Essential thrombocythemia (ET) and polycythemia vera (PV) participants from studies other than IMG-7289-202/MK-3543-005 must have achieved confirmed hematologic remission. No hypothesis testing will be conducted in this study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that participants should not have received prohibited concomitant medications. It's best to discuss your current medications with the trial team to see if they are allowed.

What makes the drug Bomedemstat unique for treating blood disorders?

Bomedemstat is unique because it targets LSD1, an enzyme involved in cell cycle regulation and differentiation, which is a promising approach for treating blood disorders. Unlike some other LSD1 inhibitors, Bomedemstat has been optimized for better stability and reduced side effects, making it a novel option in this therapeutic area. ^{1 2 3 4 5}

Research Team

Medical Director

Principal Investigator

Merck Sharp and Dohme LLC

Eligibility Criteria

This trial is for people with certain blood disorders like Polycythemia, Essential Thrombocythemia, or Myelofibrosis who have been part of previous bomedemstat studies. They must be able to take oral medication and have shown benefits from at least 6 months of prior treatment with bomedemstat.

Inclusion Criteria

I can take pills and follow home dosing instructions.

I am part of a bomedemstat study by Imago Biosciences or MSD, approved for MK-3543-017.

I've been on bomedemstat for 6+ months, tolerated it well, and it's working for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Transition

Participants transition from a prior study to the extension study to continue receiving bomedemstat

Up to 10 years

Follow-up

Participants are monitored for safety and efficacy of long-term bomedemstat treatment

Up to 10 years

Treatment Details

Interventions

• Bomedemstat

Trial Overview The study tests the long-term safety and effectiveness of a drug called Bomedemstat in patients who've previously responded well to it. It's an extension study without hypothesis testing, meaning they're not trying to prove a specific theory but rather gather more data.

Participant Groups

Group I: Bomedemstat Experimental Treatment 1 Intervention

Participants will receive oral capsules of bomedemstat once daily for up to 10 years, with the starting dose as the same dose that the participant was on at the time of transition from the feeder study.

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

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]

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]

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]

Viscosalactone B has been identified as a novel and selective inhibitor of lysine-specific demethylase 1 (LSD1), showing potent antiproliferative effects against various prostate cancer cell lines with IC50 values ranging from 0.72 to 3.86 μM.

In vivo studies demonstrated that viscosalactone B effectively inhibits tumor growth without causing significant cytotoxicity to major organs in nude mice, suggesting its potential as a safe treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells. Yan, G., Zhang, H., Li, Y., et al.[2023]

References

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

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

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

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

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

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

4. 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]

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

Viscosalactone B, a natural LSD1 inhibitor, inhibits proliferation in vitro and in vivo against prostate cancer cells. [2023]