A Study of Efficacy and Safety of AND017 in Patients With Myelodysplastic Syndrome

Inclusion criteria

• Diagnosed of primary myelodysplastic syndrome with a PISS-R grading of very low, low or intermediate risk and a bone marrow primitive cell count < 5%, the time frame for this grading assessment should be at least 12 weeks prior to the first dose
• Non-5q(del)-associated myelodysplastic syndrome.
• Two non-transfused hemoglobin ≥ 6.0 g/dL and < 10.0 g/dL, averaged over the screening period, at least one week and more apart, and with no more than 1.3 g/dL difference between the two Hb.
• Non-transfused subjects (NTD cohort) defined as no red blood cell transfusion in the 16 weeks prior to randomization or low transfusion load subjects defined as 3-7 pRBC units transfused in the 16 weeks prior to randomization and at least two different time points (LTB-1 cohort) or 1-2 pRBC units transfused at one time point in the 16 weeks prior to randomization ( LTB-2 cohort) (except in the case of transfusion for treatment of other comorbidities such as blood loss, surgery, etc.);
• Baseline EPO level ≤ 500 mU/mL
• Platelets ≥ 30,000 /mm3 and absolute neutrophil count ≥ 800/mm3
• Adequate liver function with:

• Total bilirubin <2 x upper limit of normal (ULN) (subjects with Gilbert's syndrome, i.e., unconjugated hyperbilirubinemia, have a total bilirubin <3 x ULN)
• Aspartate aminotransferase (AST) <3 x ULN
• Alanine aminotransferase (ALT) <3×ULN

Exclusion criteria

• Diagnosed of secondary myelodysplastic syndrome or concurrent anemia from a cause other than the primary myelodysplastic syndrome.
• Significant myelofibrosis (fibrosis ≥ 2+).
• Planned clearing chemotherapy or whole brain spinal cord radiotherapy during the study period.
• Previous diagnosis of MDS IPSS-R high or very high risk.
• Prior or planned hematopoietic stem cell transplant during the study period.
• Received granulocyte colony-stimulating factor (G-CSF), or thrombopoietin, or thrombopoietin receptor agonist therapy within 8 weeks prior to the first dose;
• Treatment with antithymocyte globulin, azacitidine, decitabine, cyclosporine, thalidomide, or lenalidomide within 12 weeks prior to the first dose.
• The presence of active infection or inflammatory disease requiring systemic anti-infective therapy, including concomitant autoimmune disease with inflammatory symptoms (e.g., generalized erythema, ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, dry syndrome, celiac disease, etc.)
• Concurrent retinal neovascularization requiring treatment (diabetic proliferative retinopathy, age-related exudative macular degeneration, retinal vein occlusion, macular edema, etc.)
• Inability to take oral medications, or a history of gastrectomy, concomitant gastroparesis, or other conditions that may have an impact on the absorption of gastrointestinal medications (excluding gastric polyps or colonic polypectomy)
• Clinically significant bleeding (including transfusions required to treat bleeding or bleeding resulting in a decrease in hemoglobin ≥ 2 g/dL) within 4 weeks prior to the first dose, or a bleeding constitutional or bleeding risk that has not been medically or surgically corrected.
• Uncontrolled hypertension (more than one-third of identifiable diastolic blood pressure values ≥ 100 mmHg and/or systolic blood pressure ≥ 160 mmHg at 16 weeks prior to and including screening testing)
• Comorbid heart failure (New York Heart Association [NYHA] class III or higher)
• Medical history of significant liver disease or active liver disease at screening assessment
• Have been treated with any other hypoxia-inducing factor-prolyl hydroxylase inhibitor (HIF-PHI) in the 8 weeks prior to the first dose
• Have been treated with an erythropoietic ESA within 8 weeks prior to the first dose
• Have been treated with an androgenic anabolic steroid, testosterone enanthate or methandrostenolone within 8 weeks prior to the first dose
• Have been treated with an iron chelator within 8 weeks prior to the first dose