HMPL-523 for Low Platelet Count

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, HMPL-523 (Sovleplenib), for individuals with low platelet counts due to immune thrombocytopenia (ITP), a condition that causes easy bruising and bleeding. The trial aims to determine the safety and effectiveness of HMPL-523 by exploring different doses to identify the optimal one. Suitable participants have had ITP for at least three months and have not responded well to other treatments. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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.

Is there any evidence suggesting that HMPL-523 is likely to be safe for humans?

Research shows that HMPL-523, also known as sovleplenib, is generally safe for humans. Earlier studies found that people with chronic immune thrombocytopenia, a condition causing low platelet counts, experienced a significant and lasting increase in platelets with this treatment. Importantly, no deaths occurred in these studies. Safety data from 41 patients who received various doses of HMPL-523 indicated it was well-tolerated. Although this trial remains in its early stages, these results suggest that HMPL-523 holds promise for treating low platelet counts. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for low platelet count, such as corticosteroids or immunoglobulins, HMPL-523 works by specifically targeting spleen tyrosine kinase (SYK), a key player in immune system signaling pathways. This targeted approach is designed to more precisely modulate the immune response, potentially reducing side effects associated with broader immune suppression. Researchers are excited about HMPL-523 because it offers a novel mechanism of action that could provide a more effective and safer option for patients with low platelet counts.

What evidence suggests that HMPL-523 might be an effective treatment for low platelet count?

Research shows that HMPL-523, also known as sovleplenib, may help treat low platelet counts, which is crucial for conditions like ITP (immune thrombocytopenia). In earlier studies, 80% of patients responded positively to the treatment, with improved platelet counts. Many of these patients maintained stable platelet levels, remaining above the critical threshold of 50 billion per liter. The drug stabilizes platelet counts by blocking Syk, a protein involved in the immune system. These findings suggest that HMPL-523 could effectively manage low platelet counts in ITP. Participants in this trial will engage in a dose escalation and optimization study to determine the most effective dosing strategy for HMPL-523. ^{1 2 3 5 6}

Who Is on the Research Team?

William Schelman, MD, PhD

Principal Investigator

Hutchmed

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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, 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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38885672/

Efficacy and safety of sovleplenib (HMPL-523) in adult ... Frequent TEAEs of grade 3 or higher for sovleplenib versus placebo were platelet count decreased (7% [9/126] vs 10% [6/62]), neutrophil count decreased (3 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524171467

Preclinical Pharmacology Characterization of Sovleplenib ... At 300 mg QD, sovleplenib produced an encouraging overall response rate (80%) and a durable response rate (40%) (Liu et al., 2023; Yang et al., 2021; Ali et al.

3. hutch-med.com hutch-med.com/hmpl-523-2021-ash/

HUTCHMED Highlights HMPL-523 Clinical Data ... In total, 16 out of 20 patients (80%) experienced response during both phases of the study. Durable response, defined as platelet count being ≥ 50×109/L in at ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05029635

NCT05029635 | Phase III Study on HMPL-523 for ... The purpose of this study is to determine whether HMPL-523 (sovleplenib) is safe and effective in the treatment of chronic Immune Thrombocytopenic Purpura (ITP) ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37028433/

Sovleplenib (HMPL-523), a novel Syk inhibitor, for patients ... The main efficacy endpoint was the proportion of patients whose platelet count reached 30 × 109 platelets per L or higher and was double of the baseline at two ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06291415?cond=Immune%20Thrombocytopenia&aggFilters=status:not%20rec%20act%20enr,studyType:int&intr=HMPL-523&rank=2

Study Details | NCT06291415 | The Safety, Tolerability, ... This is an open-label, multicenter study to evaluate the safety, tolerability, and efficacy of HMPL-523 in adult subjects with ITP. Detailed Description. This ...