The Safety and Efficacy Study of Avatrombopag Switch in TPO-RA Refractory AA

Study Overview
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Brief Summary
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This study was a single-arm, multicenter, phase Π clinical study. Patients admitted to the enrollment unit center with a confirmed diagnosis of TDNSAA/VSAA/SAA, treated with IST (p/r-ATG+CSA) in combination with TPO-RA (including eltrombopta or hydtrombopta) for at least 3 months with no hematologic response at 6-month follow-up, and who were not suitable or unwilling to undergo hematopoietic stem cell transplantation (HSCT), were to another novel TPO-RA avatrombopta, 40-60 mg (weight <80 kg), in addition to maintaining the original immunosuppressive therapy ( CSA or equivalent immune potency drugs), switch to another new TPO-RA avatropa 40-60 mg (40 mg daily for weight <80 kg; 60 mg daily for weight >80 kg) orally once daily for at least 3 months and follow up for 3 months to determine the hematologic response and to assess the safety of the drug

Detailed Description
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This study was a single-arm, multicenter, phase Π clinical study. Patients admitted to the enrollment unit center with a confirmed diagnosis of TDNSAA/VSAA/SAA, treated with IST (p/r-ATG+CSA) in combination with TPO-RA (including eltrombopta or hydtrombopta) for at least 3 months with no hematologic response at 6-month follow-up, and who were not suitable or unwilling to undergo hematopoietic stem cell transplantation (HSCT), were to another novel TPO-RA avatrombopta, 40-60 mg (weight <80 kg), in addition to maintaining the original immunosuppressive therapy ( CSA or equivalent immune potency drugs), switch to another new TPO-RA avatropa 40-60 mg (40 mg daily for weight <80 kg; 60 mg daily for weight >80 kg) orally once daily for at least 3 months and follow up for 3 months to determine the hematologic response and to assess the safety of the drug.Selection of study population Severe aplastic anemia patients with poor efficacy of IST combined with TPO-RA Patients should be judged for inclusion and exclusion criteria. Number of subjects: 35 effective cases, 39 patients should be included according to the dropout rate of 10%.

Official Title
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Avatrombopag in TPO-RA Refractory Aplastic Anemia Patients Safety and Efficacy Study --Single-arm, Multicenter, Open, Phase Π Clinical Study

Conditions
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Refractory Aplastic Anemia

Intervention / Treatment
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* Drug: avatrombopag


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects eligible for inclusion in this study must meet all of the following criteria: Patients with confirmed TDNSAA/SAA/VSAA aplastic anemia who received standard IST therapy for at least 6 months, combined with Haitrombopag (15mg/d) or Eltrombopag (>50mg/d) for at least 3 Patients who have not obtained a hematological response (NR) for months and are not suitable or unwilling to undergo HSCT Age > 14 years old, male or female. Subjects must complete all screening assessments listed in the trial protocol. ECOG score ≤ 2 points. Before the start of the research procedure, the patient or guardian should fully understand the research procedure and purpose and sign the informed consent form. If the patient's signature is not conducive to the treatment of the disease, the patient's immediate family should sign the informed consent form. Exclusion Criteria: Subjects meeting any of the following criteria were excluded from this study: Patients with severe infectious diseases (uncured tuberculosis, pulmonary aspergillosis, various bacterial and viral infections) and active bleeding that cannot be controlled after standard treatment. Patients with AIDS, active viral hepatitis B, and hepatitis C RNA nucleic acid test positive. Those who are pregnant or breastfeeding, have fertility but are unwilling to take effective contraceptive measures. Congenital hematopoietic failure diseases (such as Fanconi anemia). Patients with cytogenetic clonal changes (excluding germline mutations and acquired chromosome clones of +8, 20q- and -y). Combined with malignant tumor within 3 years. Combined with other systemic diseases that cannot be controlled. Significant abnormalities in cardiopulmonary function. Abnormal liver and kidney function: creatinine level > 1.5 times the upper limit of normal, transaminase and bilirubin level > 2 times the upper limit of normal, and those who cannot be enrolled in the group as judged by the clinician. Those who are considered unsuitable for enrollment by the investigator.

Ages Eligible for Study
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Minimum Age: 14 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: Avatrombopag in RAA<br>After the patients met the above-mentioned inclusion conditions and signed informed consent, they began to be included in this program. The main research objectives are to take avatrombopag conversion therapy for at least 3 months, to monitor hematological indicators, biochemical indicators and bone marrow related tests, to determine hematological responses, and to evaluate the safety of the drug. In the 6th and 12th months after treatment, comprehensive review of bone marrow and peripheral blood was performed to evaluate the recovery of hematopoiesis, determine the curative effect, evaluate adverse events, and whether there was clonal transformation. After the patients completed the main study observation, they were followed up for at least 3 months, that is, from the time the patients were enrolled, for a total of at least 6 months of follow-up. | Drug: avatrombopag<br>* Avatrombopag, 40-60 mg (body weight < 80 kg, 40 mg per day; body weight > 80 kg, 60 mg per day) orally once daily for at least 3 months and followed up for 3 months to determine hematological response and evaluate the drug security.<br>* Other names: CSA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of HR in patients after switching to avatrombopag. | Percentage of the total number of patients receiving treatment who received APAG | 3 months | 
| Incidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading | Incidence of Treatment-Emergent AE by CTCAE | 3 months | 
| Percentage of patients with transformation | Rate of patients with transformation to PNH or MDS,AML, or other disease | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of HR in patients after switching to avatrombopag. | Percentage of the total number of patients receiving treatment who received APAG | 6months | 
| ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading | Incidence of Treatment-Emergent AE by CTCAE | 6months | 
| Percentage of patients with transformation | Rate of patients with transformation to PNH or MDS,AML, or other disease | 6months | 
| The rate of HR in patients after switching to avatrombopag. | Percentage of the total number of patients receiving treatment who received APAG | 12months | 
| ncidence of Treatment-Emergent Adverse Events as assessed by information on Common Toxicity Criteria (CTC) AE grading | Incidence of Treatment-Emergent AE by CTCAE | 12months | 
| Percentage of patients with transformation | Rate of patients with transformation to PNH or MDS,AML, or other disease | 12months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Avatrombopag, TPO-RA, refractory aplastic anemia