T42486a Randomized 01-Dec-2015 Open-Label Study of PVS_TC_016_01_10232025133037 in Subjects with My

Inclusion Criteria

• Inclusion Criteria:
• • Subjects 18 years of age or older.
• • Subjects must be diagnosed with MDS according to the World Health Organization (WHO) classification for de novo or primary MDS (Vardiman et al 2009).
• • Subjects who require RBC transfusions or are either refractory to or unlikely to respond to ESA therapy should meet one of the following criteria:
• *ESA failure as defined by no improvement in Hgb of at least 1.5 g/dL after 8 weeks of at least 40,000 IU per week of EPO (or equivalent).
• *Have a serum erythropoietin (EPO) of ≥ 500 IU and Hgb level < 10.0 g/dL.
• *Transfusion dependence defined as requiring at least 4 units of packed red blood cells (RBCs) for a Hgb of < 9 g/dL over the 8 weeks prior to screening.
• • Subjects may not have received hypomethylating agents or immunosuppressive therapy for their MDS prior to this study.
• Exclusion Criteria:
• • Subjects at high risk for transformation to acute leukemia as evidenced by poor karyotype or peripheral blood blasts > 10%.
• • Subjects with severely compromised bone marrow function as evidenced by trilineage cytopenias with anemia (Hgb < 10 g/L, platelets < 100 × 109/L, and absolute neutrophil count (ANC) < 1.8 × 109/L).
• • Subjects who harbor the 5q deletion chromosomal aberration.
• • Subjects with chronic myelomonocytic leukemia (CMML).
• • Women who are pregnant or breastfeeding, and men and women who cannot comply with requirements to avoid fathering a child or becoming pregnant, respectively.
• • Subjects with impaired liver function, end stage renal disease on dialysis, or clinically significant concurrent infections requiring therapy.
• • Subjects with unstable cardiac function.
• • Invasive malignancies over the previous 2 years except treated basal or squamous carcinomas of the skin, completely resected intraepithelial carcinoma of the cervix, Stage 1 or 2 treated prostate