Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia

Study Overview
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Brief Summary
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This is a prospective one arm study to explore the efficacy and safety of Hetrombopag in non-severe aplastic anemia. Patients meeting the inclusion and exclusion criteria would be recruited. Treatment of Hetrombopag would be started with 5mg/day. The dosage would be increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L. The maximum dosage is 15mg/day. All patients would receive treatment for at least 6 months except that the platelet <20×10e9/L at the dosage of 15mg/day for 4 weeks or the platelet ≥200×10e9/L at the dosage of 5mg/week for 2 weeks. The hematological response rate and safety will be recorded and compared at D15, 1month, 1.5month, 2month, 3month, 4month, 5month, 6month, 8month, 10month and 1year.

Official Title
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Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia: a Prospective Single Arm Study

Conditions
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Aplastic Anemia, Drug Effect

Intervention / Treatment
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* Drug: Hetrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed to be non-severe aplastic anemia Patients with platelet count < 30×109/L and have at least one of the followings: ①absolute neutrophil count < 1.5×109/L, ②platelet count < 50×109/L, ③ hemoglobin level < 100g/L Patients have no response or relapsed following at least one treatment course in a period time of > 6 months of immunosuppression containing CsA or CsA+anti-thymocyte globulin (ATG); Eastern Cooperative Oncology Group (ECOG) performance status 0-2; Patients able to understand and comply with protocol requirements and instructions and have signed and dated informed consent. Exclusion Criteria: Congenital aplastic anemia; Presence of chromosomal aberration; Evidence of a clonal hematologic bone marrow disorder (MDS, AML) on cytogenetics; Presence with PNH clone ≥50%; Patients received HSCT before; Uncontrolled infection or bleeding with standard treatment; Allergic to Hetrombopag or accessories; HIV, HCV or HBV active infection or liver cirrhosis or portal hypertension; Patient with QTcF (Fridericia's QT correction formula) at screening <450 msec, or<480 msec with bundle branch block, as determined via the mean of a triplicate ECG and assessed at site, unstable angina pectoris, uncontrolled hypertension(>180/100mmHg)，pulmonary artery hypertension; Have any concomitant malignancies within 5 years expect for local basal cell carcinoma of the skin; Past history of thromboembolic event, heart attack or stroke (including anti-phospholipid antibody syndrome) and current use of anticoagulants; Pregnant or nursing (lactating) woman; Have attended other clinical trials within 3 months;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: treatment group<br>Hetrombopag would be started with 5mg/day. The dosage would be increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L. The maximum dosage is 15mg/day. | Drug: Hetrombopag<br>* Hetrombopag starting at 5mg/day and increased by 2.5mg/day every 2 weeks if the platelet count remains less than 20×10e9/L and reduced if the platelet count reaches over than 150×10e9/L.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR at 6 Months | Overall Response Rate (ORR) Defined as the Number of Participants Who Met the Criteria of Either Complete Response (CR) or Partial Response (PR) at 6 months | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR at 3 Months | ORR will be calculated after 3 months of treatment by measuring platelet, reticulocyte, neutrophil and transfusion independence. | 3 month | 
| Volume of Platelet Transfusions | Volume of Platelet Transfusions every month | 12 months | 
| percentage of side effects at 12 months | percentage of side effects would be recorded during the study and be calculated according to CTCAE 5.0 at 12 months | 12 months | 
| Percentage of patients with clonal evolution at 12 months | Percentage of patients with clonal evolution would be evaluated by bone marrow biopsy at 12 months follow up. | 12 months |