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An Open-label, Single-arm, Multicenter Phase 2/3 Clinical Trial Evaluating Avatrombopag in Adult Patients with Aplastic Anemia (AA) Refractory to or Ineligible for Immunosuppressive Therapy or with Relapsed AA after Immunosuppressive Therapy

Basic Information

Recruitment status	Pending
Health condition(s) or Problem(s) studied	Aplastic anemia
Date of first enrollment	29/05/2026
Target sample size	9
Countries of recruitment	South Korea,Japan,Taiwan,Japan
Study type	Interventional
Intervention(s)	Trial participants will receive an initial dose of 60 mg avatrombopag once daily. The dose and dosing frequency (maximum dose: 80 mg once daily; minimum dose: 20 mg three times a week) may be adjusted based on the participant's individual platelet counts. Trial participants who are being treated with moderate or strong dual inhibitors of CYP2C9 and CYP3A4/5 will receive an initial dose of 60 mg avatrombopag three times a week, and their dose and dosing frequency can be adjusted (maximum dose: 80 mg three times a week; minimum dose: 20 mg once weekly) based on their individual platelet counts.

Outcome(s)

Primary Outcome

A hematological response at Week 26 Definition of a hematological response: Achieving uni- or multilineage response by one or more of the following criteria: o Platelet response is defined as meeting at least one of the following criteria 1. Platelet count increase of >=20*10^9/L from baseline; 2. Platelet count increase of >=10*10^9/L with an increase of >=100% from baseline; or 3. Absence of platelet transfusions for 8 consecutive weeks in trial participants who had received platelet transfusions during the 8 weeks prior to the first avatrombopag dose. o Erythrocyte response is defined as meeting either of the following criteria 1. Baseline hemoglobin of <9.0 g/dL with an increase of >=1.5 g/dL from baseline (without RBC transfusions); or 2. Cumulative volume of RBC transfusion for 8 consecutive weeks is reduced by 800 mL in trial participants who had received RBC transfusions during the 8 weeks prior to first avatrombopag dose. o Neutrophil response is defined as meeting either of the following criteria 1. If baseline neutrophil <0.5*10^9/L, increase by >=100% from baseline; or 2. If baseline neutrophil <1.0*10^9/L, increase by >=0.5*10^9/L from baseline.

Secondary Outcome

Secondary efficacy endpoints include the following: 1. Time to first hematological response defined as the number of days from baseline to first improvement in at least one of the three blood cell lineages (RBCs, platelets, and neutrophils) 2. Hematological response at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, and 26 in the Primary Investigation Phase (Core Phase) and every 4 weeks in the Extension Phase. 3. Duration of hematological response: Time from first documented response to loss of response on two consecutive scheduled assessments or at EOT. 4. Changes from baseline in Quality of Life (QOL) assessed using the EORTC QLQ-C30 questionnaire at Weeks 4, 8, 12, 18, and 26 in the Primary Investigation Phase (Core Phase) and every 4 weeks in the Extension Phase. 5. Transfusion requirements (RBC and platelet units) at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, and 26 in the Primary Investigation Phase (Core Phase) and every 4 weeks in the Extension Phase. 6. Medical resource utilization: Need for medical resource utilization, including the number, reason for, and duration of hospitalizations and admissions to intensive care units at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, and 26 in the Primary Investigation Phase (Core Phase) and every 4 weeks in the Extension Phase. Safety endpoints include the following: 1. Treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and AEs of special interest (AESIs) 2. Bleeding events: Assessed using WHO Bleeding Scale 3. Clinical laboratory tests: Changes from baseline in hematology, chemistry, and other routine safety labs, identification of abnormal laboratory results, and evaluation of laboratory grade shifts at each visit. 4. Vital signs: Sitting systolic and diastolic blood pressure, pulse rate, respiration rate, and temperature, as well as change from baseline at each visit. 5. 12-lead ECG parameters (all participants): heart rate (HR), PR interval, QRS duration, and QT interval corrected by Fridericia's formula (QTcF) at Screening, Day 1 at pre-dose and at 6-7 hours post-dose. 6. 12-lead ECG parameters (participants treated with avatrombopag 80 mg): o HR, PR interval, QRS duration, and QTcF at pre-dose and 6-7 hours post-dose on the first day of their 80 mg dosing regimen. o Categorical outliers for HR, PR interval, QRS, and QTcF. o Changes of ECG morphology. 7. Bone marrow morphology: Changes from baseline in bone marrow cellularity and reticulin fibrosis grade (MF-0 to MF-3, WHO/European Consensus Reticulin Fibrosis Grading System), and evaluation of grade shifts. 8. Disease transformation: Transformation to acute myeloid leukemia (AML) and/or myelodysplastic syndrome (MDS) according to WHO/ICC criteria.

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	Patients who meet all of the following criteria will be eligible to participate: 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 examinations. 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*10^9/L. 6. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) score 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 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.
Exclude criteria	Patients who meet any of the following criteria will not be eligible to participate in the trial: 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 (MF0 to MF3) 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%) nondysplastic 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, 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 halflives (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.