A Study of Safety and Efficiency of AND017 in Patients With β-thalassemia

Prior treatment

• Presence of active infection or inflammatory disease requiring systemic anti-infective therapy, including concomitant autoimmune diseases with inflammatory symptoms (e.g. generalized erythema, ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, dry syndrome, etc.)
• history of stroke, transient ischemic attack (TIA), myocardial infarction, thromboembolic event (deep vein thrombosis, DVT), pulmonary embolism, or pulmonary infarction within 24 weeks prior to screening evaluation

Other illness

• Other causes of anemia (e.g., hemolytic anemia, history of pure red blood cell aplastic anemia, myelodysplastic syndrome, or multiple myeloma)
• Inability to take oral medications, conditions with a history of gastrectomy/bowel resection that may have an effect on the absorption of gastrointestinal medications (excluding gastric polyps or colonic polypectomy), or gastroparesis that remains symptomatic on current therapy
• Uncontrolled hypertension, defined as a diastolic blood pressure value \>95 mmHg or a systolic blood pressure \>160 mmHg on 2 or more of 3 repeated blood pressure tests (each at least 5 minutes apart) during the screening period
• Complicated congestive heart failure (New York Heart Association \[NYHA\] class III or higher).
• History of epilepsy or any past seizures.

Lab values

• Clinically significant bleeding (requiring emergency blood transfusion within 12 h or a decrease in hemoglobin ≥ 2 g/dL within one week) within 4 weeks prior to the first dose, or a tendency to bleed or risk of bleeding that has not been medically or surgically corrected
• history of significant coagulation abnormalities, or platelet count \>600 x 109/L or \<80 x 109/L

Age

• Complicated retinal neovascularization requiring treatment (diabetic proliferative retinopathy, age-related exudative macular degeneration, retinal vein occlusion, macular edema, etc.)

• Documented diagnosis of β-thalassemia or hemoglobin E/β-thalassemia, HbS/ β-thalassemia (β-thalassemia with α-bead mutation and/or multiplication is not allowed).
• TDT subjects: receive regular blood transfusions, defined as 6-20 RBC units (including threshold) in the 24 weeks prior to screening assessment, and no transfusion-free period of ≥ 5 weeks during this period.
• NTDT cohort: having transfused \<6 RBC units in the 24 weeks prior to the screening assessment, no regular transfusion schedule, and no transfusion for 4 weeks prior to the screening assessment.
• Subject transfusion records should be obtained within 24 weeks prior to the screening assessment, containing the date of transfusion, transfused RBC units, and pre-transfusion hemoglobin values.
• ECOG score 0-1.
• NTDT subjects with Hb ≤ 10.0 g/dL at screening test and one follow-up test (two tests more than one week apart) and difference in values between the two tests ≤ 1.0 g/dL.
• Adequate liver function: Total bilirubin \< 1.5 x upper limit of normal (ULN) (subjects with Gilbert syndrome, i.e., unconjugated hyperbilirubinemia, have a total bilirubin \< 3 x ULN), aspartate aminotransferase