Bomedemstat for Myeloproliferative Disorders

Recruiting at 18 trial locations

Overseen By Jennifer Peppe

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Imago BioSciences,Inc.

Must not be taking: Romiplostim

Disqualifiers: Pregnancy, Breastfeeding, Non-compliance, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

81 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing the safety and effectiveness of bomedemstat, a daily oral medication, in patients with a blood disorder called MPN. The drug works by controlling blood cell production.

Do I need to stop taking my current medications for the trial?

You may need to stop taking certain medications, as the trial excludes participants using prohibited medications like romiplostim. It's best to discuss your current medications with the trial team to see if any need to be stopped.

What data supports the effectiveness of the drug Bomedemstat for treating myeloproliferative disorders?

Research on the drug IMG-7289, which is another name for Bomedemstat, shows that it can improve survival and reduce disease symptoms in mouse models of myeloproliferative disorders by targeting specific disease cells and improving blood cell counts and spleen size. ^{1 2 3 4 5}

How is the drug Bomedemstat unique for treating myeloproliferative disorders?

Bomedemstat is unique because it is a LSD1 inhibitor, which means it targets a specific enzyme involved in regulating gene expression, potentially offering a novel approach compared to existing treatments for myeloproliferative disorders. ^{6 7 8 9 10}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for patients with myeloproliferative disorders who have already completed a treatment period in a previous bomedemstat study. They must be assessed by the investigator as suitable for continued dosing and agree to use contraception. Excluded are those on certain medications, unable to consent or comply, pregnant or breastfeeding women, participants in other trials, and anyone non-compliant in past studies.

Inclusion Criteria

Completed at least one Treatment Period (TP) in a prior bomedemstat MPN protocol (such as, but not limited to, IMG-7289-CTP-102 or IMG-7289-CTP-201)

In the estimation of the Investigator, the risk-benefit favors continued dosing with bomedemstat

Exclusion Criteria

I agree to use birth control from enrollment until 14 days after my last dose.

I am not pregnant, breastfeeding, nor planning to during the study.

Ongoing participation in another investigational study (except observational studies)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bomedemstat daily for 169 days with additional treatment continuing in participants deriving clinical benefit

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

Open-label extension

Participants continue to receive bomedemstat to assess long-term safety and efficacy

Long-term

Treatment Details

Interventions

• Bomedemstat

Trial Overview The trial tests the long-term safety and effectiveness of an oral drug called bomedemstat (MK-3543) for people with blood disorders like primary myelofibrosis and essential thrombocythemia. It's an extension study for those who've been part of prior related research.

Participant Groups

Group I: Bomedemstat Experimental Treatment 1 Intervention

Participants will receive bomedemstat daily for 169 days with additional treatment continuing in participants deriving clinical benefit.

Who Is Running the Clinical Trial?

Imago BioSciences,Inc.

Lead Sponsor

Trials

10

Recruited

380+

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

Lead Sponsor

Trials

10

Recruited

380+

Findings from Research

TG101348, a selective JAK2 inhibitor, demonstrated significant therapeutic effects in a mouse model of myeloproliferative disease caused by the JAK2V617F mutation, including reduced hematocrit and leukocyte counts.

The treatment showed no apparent toxicities and did not affect T cell numbers, indicating a favorable safety profile while effectively targeting the disease at the molecular level.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Wernig, G., Kharas, MG., Okabe, R., et al.[2022]

The discovery of the JAK2V617F mutation has led to significant advancements in the treatment of myeloproliferative neoplasms (MPN), particularly with the development of JAK inhibitors like Ruxolitinib, which has shown effectiveness in reducing spleen size and improving quality of life in patients with myelofibrosis (MF).

In addition to JAK inhibitors, other innovative treatments such as immunomodulatory drugs (like pomalidomide), kinase inhibitors, and HDAC inhibitors are being explored in clinical trials, suggesting a promising future for combination therapies in MPN management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Novel therapeutic options in the treatment of BCR/ABL-negative myeloproliferative neoplasms]. Döhner, K., Stegelmann, F., Schlenk, RF., et al.[2021]

In a study involving 39 lower risk MDS patients, the thrombopoietin mimetic romiplostim reduced the incidence of clinically significant thrombocytopenic events (CSTEs) compared to placebo, suggesting it may help manage lenalidomide-induced thrombocytopenia.

Patients receiving romiplostim had fewer dose reductions or delays in lenalidomide treatment due to low platelet counts, indicating that romiplostim could improve the tolerability of lenalidomide therapy in MDS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide. Wang, ES., Lyons, RM., Larson, RA., et al.[2021]

In a study of 40 patients with low- or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine, romiplostim showed a lower incidence of clinically significant thrombocytopenic events compared to placebo, with rates of 62% and 85%, respectively.

Romiplostim at a dose of 750 μg significantly increased median platelet counts during treatment, indicating potential clinical benefits for MDS patients, although the differences in thrombocytopenic events were not statistically significant due to small sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. Kantarjian, HM., Giles, FJ., Greenberg, PL., et al.[2021]

References

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

Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. [2022]

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

LSD1 Inhibition Prolongs Survival in Mouse Models of MPN by Selectively Targeting the Disease Clone. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Novel therapeutic options in the treatment of BCR/ABL-negative myeloproliferative neoplasms]. [2021]

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

p53 at the crossroads of MPN treatment. [2021]

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

Targeting pleckstrin-2/Akt signaling reduces proliferation in myeloproliferative neoplasm models. [2023]

6. England pubmed.ncbi.nlm.nih.gov

A randomized, double-blind, placebo-controlled phase 2 study evaluating the efficacy and safety of romiplostim treatment of patients with low or intermediate-1 risk myelodysplastic syndrome receiving lenalidomide. [2021]

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

Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Clinical management of myelodysplastic syndromes: update of SIE, SIES, GITMO practice guidelines. [2018]

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

Feasibility of pevonedistat combined with azacitidine, fludarabine, cytarabine in pediatric relapsed/refractory AML: Results from COG ADVL1712. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Current status of phase 3 clinical trials in high-risk myelodysplastic syndromes: pitfalls and recommendations. [2023]