AVA-AA-350

Adults ≥18 with bone-marrow–confirmed aplastic anemia, refractory/relapsed after ≥1 IST course (incl. ATG) or ATG-ineligible and refractory/relapsed after CyA, platelets ≤30×10⁹/L, ECOG 0–2.

Primary Investigation Phase (Core Phase) 1. Patients must be able to provide informed consent. 2. Age ≥18. 3. Diagnosis of aplastic anemia confirmed by peripheral blood and bone-marrow aspirate/biopsy. 4. Refractory to or relapsed after at least one course of immunosuppressive therapy including horse or rabbit anti-thymocyte globulin (ATG); or ineligible for ATG treatment and refractory to or relapsed after cyclosporine A (CyA). 5. Thrombocytopenia defined as a platelet count of ≤ 30 × 10⁹/L. 6. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) score (refer to Appendix D) of 0 to 2 at screening. 7. Women of childbearing potential must have a negative pregnancy test at screening and baseline. 8. Patients who agree to use an effective method of contraception, as defined in Section 6.4.4, from the time of informed consent until 30 days after the final dose of avatrombopag. Extension Phase 1. No significant safety or tolerability concerns with the trial participant's participation in the Primary Investigation Phase (Core Phase) as determined by the Investigator.

Excludes MF-2/3 fibrosis, >2% blasts, MDS cytogenetics, inherited marrow failure, other-cause thrombocytopenia, hemolytic/large PNH clone, recent cancer, thromboembolism, prior TPO-RA/HSCT, CrCl ≤30.

Primary Investigation Phase (Core Phase) 1. Patients with bone marrow fibrosis MF-2 or MF-3 at screening, graded according to the WHO/European Consensus Reticulin Fibrosis Grading System (MF-0 to MF-3; Appendix E) documented on a bone marrow aspirate/biopsy obtained during screening. 2. Patients with >2% bone marrow blasts documented on a bone marrow aspirate/biopsy obtained during screening. 3. Patients with MDS-defining cytogenetic abnormalities per WHO 2022 (5th Edition), including −7/del(7q), −5/del(5q), complex (≥3) or monosomal karyotype, 3q26/EVI1 rearrangements, and other recognized MDS/AML-defining lesions, or with unequivocal dysplasia/blast excess; isolated +8, −Y, del(20q), or small (<10%) non-dysplastic clones are eligible with enhanced surveillance. 4. Patients with a history of cirrhosis, portal hypertension, chronic active hepatitis. 5. Patients with clinically significant cardiac disease (class III or IV of the New York Heart Association classification); unstable angina pectoris; myocardial infarction within 6 months before enrollment; cardiac disease accompanied by angioplasty or stenting within 6 months before enrollment; or clinically significant cardiac arrhythmias, including history of torsades de pointes; uncontrollable hypertension. 6. Patients with known diagnosis or clinical suspicion of inherited bone marrow failure syndrome, including but not limited to Fanconi Anaemia. 7. Patients with thrombocytopenia due to any other causes (e.g., myelodysplastic syndrome [MDS], idiopathic thrombocytopenic purpura, human immunodeficiency virus [HIV], hepatitis C virus [HCV], systemic lupus erythematosus [SLE], or cirrhosis). 8. Patients with concurrent occurrence of hemolytic predominant paroxysmal nocturnal haemoglobinuria (PNH). Hemolytic predominant is defined as lactate dehydrogenase >1.5 times the upper limit of the laboratory normal range. 9. Patients with a clinically significant PNH clone size, defined as a granulocyte or monocyte PNH clone ≥50% or any clone size considered by the Investigator to confer increased thrombosis risk (e.g., rapid expansion or laboratory evidence of active hemolysis). 10. Patients with PNH being treated with a complement-inhibiting therapy, including C5 inhibitors, C3 inhibitors, or proximal complement pathway inhibitors. 11. Patients with a history of malignant disease within the past 5 years, or with concurrent malignant disease or receiving cytotoxic chemotherapy for a reason other than AA treatment (except for basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix). 12. Patients with medical history of thromboembolism within 6 months or current use of anticoagulants. Patient with antiphospholipid antibody syndrome (APS). 13. Pregnant or breastfeeding women, and women of childbearing potential who are unwilling or unable to use effective contraception as defined in Section 6.4.4, or who have a positive pregnancy test at screening or baseline. 14. Patients with known allergy to avatrombopag or any of its excipients. 15. Patients with creatinine clearance ≤30 mL/min calculated using the Cockroft and Gault formula. 16. Patients receiving any medication or treatment for AA, including the following before avatrombopag treatment initiation: o Use of ATG (either horse or rabbit) within 90 days of Day 1/Baseline. o Use of cyclosporine A or anabolic steroid within 6 weeks of Day 1/Baseline. However, patients who have been receiving cyclosporine A or anabolic steroid at least 8 weeks before Day 1/Baseline may be enrolled if the blood cell count is stable at screening and the dosage regimen is maintained stable for 6 weeks prior to the initiation of avatrombopag treatment and during the trial treatment. o Any prior hematopoietic stem cell transplantation 17. Patients with a history of use of polyethylene glycol-conjugated recombinant human megakaryocyte growth and development factor, recombinant human TPO, or romiplostim. 18. Patients received eltrombopag within 7 days of Day 1/Baseline. 19. Patients received treatment with another investigational drug within 30 days or 5 half-lives (whichever is longer) before Day 1/Baseline. 20. Any clinically relevant abnormality which makes the patient unsuitable for participation in the trial, in the opinion of the Investigator. 21. Patients who are considered unable or unwilling to comply with the trial protocol requirements, as determined by the Investigator. Extension Phase 1. Patients for whom participation in the Extension Phase is considered inappropriate, based on the Investigator's judgment. 2. Patients considered unable or unwilling to comply with the trial protocol requirements, as determined by the Investigator.