Avatrombopag Usage in NSAA

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, open-label, prospective one arm study to explore the efficacy and safety of Avatrombopag in non-severe aplastic anemia. Patients meeting the inclusion and exclusion criteria would be recruited. Treatment of Avatrombopag would be started with 20mg/day. The dosage would be increased by 20 mg/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 dosage could range from 20mg/week to 60mg/day. All patients would receive treatment for at least 6 months except that the platelet <20×10e9/L at the dosage of 60mg/day for 4 weeks or the platelet ≥200×10e9/L at the dosage of 20mg/week for 2 weeks. The hematological response rate and safety will be recorded and compared at every month after starting the study treatment. The patients would be followed up for at least 6 months.

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

Conditions
-----------------
Aplastic Anemia, Drug Effect

Intervention / Treatment
-----------------
* Drug: Avatrombopag 20 MG


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients diagnosed to be non-severe aplastic anemia Patients have at least one of the followings: ①absolute neutrophil count < 1.5×109/L, ②platelet count < 30×109/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 Avatrombopag 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
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Avatrombopag treatment group<br>Avatrombopag would be started with 20mg/day. The dosage would be increased by 20 mg/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 dosage could range from 20mg/week to 60mg/day. | Drug: Avatrombopag 20 MG<br>* Avatrombopag 20mg/week to 60mg/day, starting at 20mg/day and increased by 20 mg/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?
-----------------
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 months | 

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 months | 
| Percentage of patients with clonal evolution at 6 months | Percentage of patients with clonal evolution would be evaluated by bone marrow biopsy at 6 months follow up. | 6 months | 
| percentage of side effects at 6 months | percentage of side effects would be recorded during the study and be calculated according to CTCAE 5.0 at 6 months | 6 months | 
| Total volume of Platelet Transfusions | Total volume of Platelet Transfusions | 1 month | 
| Total volume of Red Blood Cells Transfusions | Total volume of Red Blood Cells Transfusions | 1 month |