Bomedemstat for Essential Thrombocythemia

Recruiting at 194 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

340 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the new drug bomedemstat (an LSD1 inhibitor) outperforms current treatments for people with essential thrombocythemia (ET), a condition characterized by excessive platelet production, increasing blood clot risks. Participants will receive either bomedemstat or the best available existing therapy. The study seeks individuals with ET who have not succeeded with hydroxyurea or cannot tolerate it and have a high platelet count impacting their daily life. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that bomedemstat is likely to be safe for humans?

Research has shown that bomedemstat is generally safe for people with blood disorders like essential thrombocythemia. Previous studies indicate that many patients tolerate it well. Common side effects include mild headaches and tiredness, but these are not serious.

In another study, patients with similar conditions received bomedemstat, and it showed promising safety results. The treatment did not cause any major health problems, suggesting it might be a safe option for managing essential thrombocythemia. However, discussing any concerns with a doctor is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for essential thrombocythemia?

Bomedemstat is unique because it targets essential thrombocythemia by inhibiting an enzyme called LSD1, which plays a crucial role in controlling platelet production. This approach is different from the standard treatments like anagrelide or interferon, which mainly work by reducing platelet counts through other pathways. Researchers are excited about bomedemstat because it offers a more direct and potentially safer way to manage platelet levels without the side effects typically associated with current therapies. Additionally, its ability to have adjustable dosing may allow for more personalized treatment, enhancing its effectiveness and safety for each individual.

What evidence suggests that bomedemstat might be an effective treatment for essential thrombocythemia?

Research shows that bomedemstat, which participants in this trial may receive, may help treat essential thrombocythemia (ET). In earlier studies, patients taking bomedemstat experienced fewer symptoms and improved blood cell levels. Bomedemstat has effectively lowered platelet counts to desired levels, managing the blood disorder. These results suggest that bomedemstat could be a good option for people who haven't had success with other treatments like hydroxyurea. Another treatment arm in this trial involves the use of Best Available Therapy (BAT), which includes options such as anagrelide, busulfan, interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b, or ruxolitinib. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharpe & Dohme LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 156 weeks.

Group II: Best Available Therapy Active Control 4 Interventions

Each participant will receive either anagrelide, busulfan, interferon alfa/pegylated interferon alfa 2a/pegylated interferon alfa 2b, 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 156 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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06351631

NCT06351631 | A Study to Evaluate Safety and Efficacy of ... The study will include participants who are safely tolerating bomedemstat, receiving clinical benefit from its use in estimation of the investigator, and have ...

2. merck.com merck.com/news/merck-announces-phase-3-trial-initiation-for-bomedemstat-an-investigational-candidate-for-the-treatment-of-certain-patients-with-essential-thrombocythemia/

Merck Announces Phase 3 Trial Initiation for Bomedemstat, ... The Shorespan-003 trial is one of multiple Phase 2 clinical trials where bomedemstat is being evaluated alone and in combination for the ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01821

A Study of Bomedemstat (IMG-7289/MK-3543) Compared ... This is a study evaluating the safety and efficacy of bomedemstat (MK-3543) compared with the best available therapy (BAT) in participants with essential ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4569.3/529587/A-Phase-3-Randomized-Double-Blind-Active

A Phase 3, Randomized, Double-Blind, Active-Comparator ... In a phase 2 clinical study of patients with ET, bomedemstat improved symptoms, durably reduced PC and WCC, and reduced mutation burden. This ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000649712305351X

Bomedemstat (IMG-7289), an LSD1 Inhibitor, Manages the ... This study demonstrates that treatment with bomedemstat results in a consistent hematologic response in the majority of patients with ET.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04262141

Study Details | NCT04262141 | IMG-7289 in Patients with ... The purpose of this study is to assess the hematologic effects of IMG-7289 therapy in ET and PV patients who require platelet, White Blood Cell (WBC) or Red ...

7. targetedonc.com targetedonc.com/view/phase-3-trial-of-bomedemstat-in-essential-thrombocythemia-begins-enrollment

Phase 3 Trial of Bomedemstat in Essential ... The phase 3 Shorespan-007 trial will compare bomedemstat with hydroxyurea in patients with treatment-naive essential thrombocythemia.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04254978

NCT04254978 | Study of Bomedemstat in Participants With ... This is a Phase 2 multi-center, open-label study evaluating the safety, efficacy and pharmacodynamics of Bomedemstat administered orally once daily in patients ...

9. mpn-hub.com mpn-hub.com/medical-information/updates-of-img-7289-bomedemstat-in-treating-myelofibrosis-and-essential-thrombocythemia

Updates of IMG-7289 (bomedemstat) in treating ... Updates of IMG-7289 (bomedemstat) in treating myelofibrosis and essential thrombocythemia ... IMG-7289 (bomedemstat) is a generally safe ...

10. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06351631/a-study-to-evaluate-safety-and-efficacy-of-bomedemstat-mk-3543-017?id=1043&slug=post-essential-thrombocythemia-myelofibrosis

A Study to Evaluate Safety and Efficacy of Bomedemstat ... The primary purpose of the study is to transition participants into an extension study to collect long-term safety and efficacy data.