A Study of TQ05105 Tablets in Subjects With Hemophagocytic Lymphohistiocytosis（HLH）

Study Overview
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Brief Summary
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This is a phase I study of TQ05105 tablets in subjects with Hemophagocytic Lymphohistiocytosis.TQ05105 is a JAK2 inhibitors and can be used to treat JAK2 target-related diseases. The activation of the JAK/STAT pathway is related to abnormal proliferation, obstruction of apoptosis, and differentiation disorder of leukemia cells which is caused by genetic abnormalities and viral infection.

Official Title
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A Single-arm, Open-label, Phase I Study of TQ05105 Tablets in Subjects With Hemophagocytic Lymphohistiocytosis.

Conditions
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Hemophagocytic Lymphohistiocytosis

Intervention / Treatment
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* Drug: TQ05105


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.18 years and older; Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3; Life expectancy ≥ 3 months. 2. Diagnosed as new or relapsed HLH according to the HLH-2004 criteria. 3.Has received other treatments for HLH before two weeks ago, surgery before four weeks ago. 4. Adequate laboratory indicators. 5. No pregnant or breastfeeding women, and a negative pregnancy test. 6. Understood and signed an informed consent form. Exclusion Criteria: 1. Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. With exception of non-melanoma, skin cancer, and carcinoma in situ. 2. Has participated in other anticancer drug clinical trials within 4 weeks. 3. Has multiple factors affecting oral medication. 4. Has drug abuse history that unable to abstain from or mental disorders. 5. Has active hepatitis B or C, or immunodeficiency. 6. Diagnosed as hepatic failure. 7. Has arteriovenous thrombosis events within 4 weeks. 8. Has active bleeding, or a persistent decrease in hemoglobin. 9. Has received long-term and large-dose glucocorticoids or other immunosuppressive drugs within 28 days before signed the informed consent form. 10. Has uncontrolled cardiovascular disease. 11. Has uncontrolled hypertension. 12. Has serious systemic infections. 13. According to the judgement of the researchers, there are other factors that subjects are not suitable for the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TQ05105 Tablet<br>TQ05105 tablet administered orally once. Then TQ05105 tablet administered orally, twice daily in 28-day cycle after 3 days of first administration. | Drug: TQ05105<br>* TQ05105 is a JAK2 inhibitor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) | DLT defined as any of the events occurring during the study related to drugs. | Baseline up to 28 days | 
| Maximal tolerance dose (MTD) | MTD defined as the highest dose level at which less than or equal to 2 of 6 subjects experience dose limiting toxicity (DLT). | Baseline up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Cmax is the maximum plasma concentration of TQ05105 or metabolite(s). | Hour 0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11, 24 hours post-dose on single dose; Hour 0 of day 1,day 3,day5, day 6 on multiple dose and hour0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11 hours post-dose on multiple dose of day 28. | 
| Tmax | To characterize the pharmacokinetics of TQ05105 by assessment of time to reach maximum plasma concentration. | Hour 0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11, 24 hours post-dose on single dose; Hour 0 of day 1,day 3,day5, day 6 on multiple dose and hour0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11 hours post-dose on multiple dose of day 28. | 
| AUC0-t | To characterize the pharmacokinetics of TQ05105 by assessment of area under the plasma concentration time curve from zero to infinity. | Hour 0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11, 24 hours post-dose on single dose; Hour 0 of day 1,day 3,day5, day 6 on multiple dose and hour0, 5, 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 11 hours post-dose on multiple dose of day 28. |