HMPL-523 for Low Platelet Count

Recruiting at 27 trial locations

Overseen By Vijay Jayaprakash, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Hutchmed

Disqualifiers: Secondary ITP, Active malignancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

48 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial investigators.

What data supports the effectiveness of the drug HMPL-523 for low platelet count?

While there is no direct data on HMPL-523, similar drugs like eltrombopag and avatrombopag, which are thrombopoietin receptor agonists (drugs that help increase platelet production), have shown effectiveness in increasing platelet counts in various conditions with low platelet counts. ^{1 2 3 4 5}

What makes the drug HMPL-523 unique for treating low platelet count?

HMPL-523, also known as Sovleplenib, is unique because it specifically targets the spleen tyrosine kinase (SYK) pathway, which plays a crucial role in platelet production and immune response, offering a novel mechanism of action compared to existing treatments for low platelet count. ^{6 7 8 9 10}

What is the purpose of this trial?

This is an open-label, multicenter study to evaluate the safety, tolerability, and efficacy of HMPL-523 in adult subjects with ITP.

Research Team

William Schelman, MD, PhD

Principal Investigator

Hutchmed

Eligibility Criteria

Adults with immune thrombocytopenia (ITP), a condition where the blood doesn't clot well due to low platelet count, can join this trial. Specific details on who can or cannot participate are not provided here.

Inclusion Criteria

I have been diagnosed with ITP for at least 3 months.

I have had ITP and treatments other than splenectomy didn't work or caused side effects.

My blood, liver, and kidney functions are all within normal ranges.

Exclusion Criteria

Evidence of the presence of secondary causes of ITP

I need immediate treatment for a serious bleeding issue.

Being unsuitable to participate in this study as considered by investigators

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects receive one of 3 dose levels of HMPL-523 to determine the recommended dose for the next stage

4 weeks

Weekly visits for dose escalation assessment

Dose Optimization

Subjects are randomized between 2 dose levels to understand exposure/efficacy/toxicity relationship

20 weeks

Bi-weekly visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• HMPL-523

Trial Overview The study is testing HMPL-523's safety and how well it works in adults with ITP. It's an open-label, multicenter trial, meaning both researchers and participants know what treatment is being given.

Participant Groups

Group I: Dose optimization stage Experimental Treatment 1 Intervention

In part 2 subjects will be randomized in a 1:1 ratio between the 2 dose levels selected at the end of part 1.

Group II: Dose escalation Experimental Treatment 1 Intervention

Part 1 will consist of the following 3 dose levels: 300, 400, and 500 mg once daily (QD).

HMPL-523 is already approved in China for the following indications:

Approved in China as Sovleplenib for:

• Immune thrombocytopenic purpura (ITP)

Who Is Running the Clinical Trial?

Hutchmed

Lead Sponsor

Trials

38

Recruited

6,700+

Findings from Research

In a phase II clinical trial involving 24 patients with various inherited thrombocytopenias, the oral thrombopoietin-mimetic eltrombopag significantly increased platelet counts, with 47.8% of patients achieving a major response (platelet count >100 ×10^9/L).

Eltrombopag was well tolerated, with only mild to moderate adverse events reported, and it effectively reduced bleeding symptoms in patients, particularly those with clinically significant spontaneous bleeding, although caution is advised due to potential leukemia risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial. Zaninetti, C., Gresele, P., Bertomoro, A., et al.[2021]

In a 52-week study involving 234 adults with immune thrombocytopenia, romiplostim significantly increased the rate of platelet response compared to standard care, with a response rate 2.3 times higher (P<0.001).

Patients receiving romiplostim experienced fewer treatment failures and required splenectomy less often (11% vs. 30% for standard care, P<0.001), along with lower rates of bleeding events and improved quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Romiplostim or standard of care in patients with immune thrombocytopenia. Kuter, DJ., Rummel, M., Boccia, R., et al.[2016]

In a study of 13 cancer patients with severe and refractory chemotherapy-induced thrombocytopenia (CIT), 61.5% responded positively to avatrombopag, a thrombopoietin receptor agonist, with a median response time of 27.5 days and 76.9% no longer needing platelet transfusions by the end of the study.

Avatrombopag was found to be safe, with no drug-related side effects reported, and patients with hemoglobin levels above 90 g/L had a significantly higher response rate of 88.9%, indicating that hemoglobin levels can help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors. Gao, Y., Liu, Q., Shen, Y., et al.[2023]

In the ASPIRE trial, eltrombopag demonstrated efficacy in treating thrombocytopenia in patients with advanced myelodysplastic syndrome or acute myeloid leukemia, with 30-65% of patients experiencing clinically relevant improvements in platelet counts.

The long-term safety profile of eltrombopag was consistent with earlier studies, suggesting it may be a beneficial treatment option for thrombocytopenia in patients with low- to intermediate-risk myelodysplastic syndrome, despite the study's non-randomized design and lack of placebo control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Eltrombopag for Advanced Myelodysplastic Syndromes or Acute Myeloid Leukemia and Severe Thrombocytopenia: Results of the ASPIRE Extension Study. Mittelman, M., Platzbecker, U., Grosicki, S., et al.[2023]

In a phase 2 trial involving 90 patients with lower-risk myelodysplastic syndromes and severe thrombocytopenia, eltrombopag significantly improved platelet counts, with 47% of patients responding compared to only 3% in the placebo group.

Eltrombopag was well-tolerated, leading to fewer severe bleeding events compared to placebo (14% vs. 42%), indicating its potential to enhance safety in managing thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Oliva, EN., Alati, C., Santini, V., et al.[2018]

Idasanutlin, an MDM2 antagonist, was well tolerated in a phase 1 trial with 12 patients suffering from high-risk polycythemia vera (PV) and essential thrombocythemia (ET), showing no dose-limiting toxicity and an overall response rate of 58% after 6 treatment cycles.

The treatment led to significant hematologic and molecular responses, with a median duration of response of 16.8 months, indicating that idasanutlin could be a promising new option for patients with PV/ET who have not responded to previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral idasanutlin in patients with polycythemia vera. Mascarenhas, J., Lu, M., Kosiorek, H., et al.[2021]

Pacritinib has shown significant efficacy in treating patients with myelofibrosis and severe thrombocytopenia, outperforming the best available therapy (BAT) in key measures such as spleen volume reduction and symptom improvement in a retrospective analysis of 189 patients from the PERSIST trials.

The safety profile of pacritinib was manageable, with no increase in bleeding or mortality, making it a promising option for patients who cannot use other JAK inhibitors due to their risk of worsening thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia. Verstovsek, S., Mesa, R., Talpaz, M., et al.[2022]

Ruxolitinib, an oral JAK1/JAK2 inhibitor, has shown significant efficacy in treating patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea, as demonstrated in Phase II and III clinical trials.

Treatment with ruxolitinib resulted in normalization of blood cell counts, reduction of splenomegaly, and improvements in symptoms related to PV, addressing the need for more effective therapies in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of patients with polycythemia vera. Kiladjian, JJ., Winton, EF., Talpaz, M., et al.[2021]

Pegylated interferon (IFN), particularly ropeginterferon-α-2b, shows promise as a frontline therapy for high-risk polycythemia vera (PV), demonstrating efficient count control and tolerability in early-phase studies.

Novel therapies, including combinations of ruxolitinib and IFN, as well as MDM2 inhibitors, are being explored to potentially change the treatment approach for newly diagnosed PV patients from reactive to proactive interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic approaches in polycythemia vera. Foucar, CE., Stein, BL.[2021]

Ruxolitinib, a Janus kinase inhibitor, has shown promise as a second or third-line treatment for patients with polycythaemia vera (PV) who are resistant or intolerant to standard therapies like hydroxycarbamide, based on findings from phase II trials.

Current therapies for PV, including low-dose aspirin and phlebotomy, primarily aim to manage hematocrit levels to reduce thrombotic risks, but there is limited evidence that they prevent transformation to more severe conditions like myelofibrosis or acute myeloid leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with ruxolitinib in the treatment of polycythaemia vera. Alimam, S., Harrison, C.[2021]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Eltrombopag for the treatment of inherited thrombocytopenias: a phase II clinical trial. [2021]

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

Romiplostim or standard of care in patients with immune thrombocytopenia. [2016]

3. England pubmed.ncbi.nlm.nih.gov

Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Safety and Efficacy of Eltrombopag for Advanced Myelodysplastic Syndromes or Acute Myeloid Leukemia and Severe Thrombocytopenia: Results of the ASPIRE Extension Study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. [2018]

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

Oral idasanutlin in patients with polycythemia vera. [2021]

7. Italy pubmed.ncbi.nlm.nih.gov

Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia. [2022]

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

Ruxolitinib for the treatment of patients with polycythemia vera. [2021]

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

Novel therapeutic approaches in polycythemia vera. [2021]

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

Experience with ruxolitinib in the treatment of polycythaemia vera. [2021]