ACE-536 Extension Study - Myelodysplastic Syndromes
ACE-536 Extension Study - Myelodysplastic Syndromes
Study A536-05 is an open-label extension study for patients previously enrolled in study
 A536-03 (ClinicalTrials.gov Identifier NCT01749514), to evaluate the long-term safety and
 tolerability of ACE-536 in patients with low or intermediate-1 risk MDS.
Study A536-05 is an open-label extension study to evaluate the safety, tolerability, and
 pharmacodynamic effects of up to 24 months of ACE-536 treatment in patients with low or
 intermediate-1 risk myelodysplastic syndromes previously treated with ACE-536 for up to 3
 months in study A536-03 (ClinicalTrials.gov Identifier NCT01749514). The starting dose level
 in study A536-05 will be 1.0 mg/kg by subcutaneous (SC) injection every 3 weeks. Dose
 titration/modification rules will be followed for individual patients and will be based upon
 safety and efficacy data collected during the course of treatment.
Inclusion Criteria:

 -  Completion of the treatment period in the base study A536-03 (ClinicalTrials.gov
 Identifier:

 NCT01749514)

 -  Adequate birth control measures

 -  Patient is able to adhere to the study visit schedule, understand and comply with all
 protocol requirements.

 -  Patient understands and is able to provide written informed consent.

 In addition, patients with treatment interruption (defined as patients who complete their
 end-of-study visit in A536-03 and cannot directly roll over to A536-05) must also meet the
 following criteria:

 -  Documented diagnosis of idiopathic/de novo MDS or non-proliferative chronic
 myelomonocytic leukemia (CMML) according to the World Health Organization (WHO)
 criteria 2 (white blood count (WBC) < 13,000/μL) that meets International Prognostic
 Scoring System (IPSS) classification (Appendix 2) of low or intermediate-1 risk
 disease as determined by microscopic and standard cytogenetic analyses of the bone
 marrow and peripheral complete blood count (CBC) obtained during screening;

 -  Anemia defined as:

 -  Mean hemoglobin concentration < 10.0 g/dL of 2 measurements (one performed within one
 day prior to Cycle 1 Day 1 and the other performed 7-28 days prior to Cycle 1 Day 1),
 for non-transfusion dependent (NTD) patients (defined as having received ˂ 4 units of
 red blood cells (RBCs) within 8 weeks prior to Cycle 1 Day 1), OR

 -  Transfusion Dependent (TD), defined as having received ≥ 4 units of RBCs within 8
 weeks prior to Cycle 1 Day 1.

 -  Platelet count ≥ 30 x 109/L

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related
 to anemia)

 -  Adequate renal (creatinine ≤ 2.0 x upper limit of normal [ULN]) and hepatic (total
 bilirubin < 2 x ULN and aspartate aminotransferase (AST) and alanine aminotransferase
 (ALT) < 3 x ULN) function

 Exclusion Criteria:

 -  Discontinuation/withdrawal from the base study A536-03 (due to patient request,
 patient unwillingness or inability to comply with the protocol, pregnancy, use of
 prohibited medication [e.g. azacitidine], medical reason or adverse event (AE),
 hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss
 to follow-up) prior to completion of the treatment period

 -  Prior treatment with azacitidine or decitabine

 -  Treatment within 28 days prior to Cycle 1 Day 1 with:

 -  an erythropoiesis-stimulating agent (ESA),

 -  Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony
 stimulating factor (GM-CSF),

 -  Lenalidomide

 -  Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1

 -  Treatment with another investigational drug (including sotatercept [ACE-011]) or
 device, or approved therapy for investigational use ≤ 28 days prior to Cycle 1 Day 1,
 or if the half-life of the previous investigational product is known, within 5 times
 the half-life prior to Cycle 1 Day 1, whichever is longer

 -  Major surgery within 28 days prior to Cycle 1 Day 1. Patients must have completely
 recovered from any previous surgery prior to Cycle 1 Day 1

 -  Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B
 (HBV) or active infectious hepatitis C (HCV)

 -  Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 150 mm Hg or
 diastolic blood pressure (DBP) ≥ 100 mm Hg

 -  Pregnant or lactating females

 -  History of severe allergic or anaphylactic reactions or hypersensitivity to
 recombinant proteins or excipients in the investigational drug

 -  Any other condition not specifically noted above which, in the judgment of the
 investigator, would preclude the patient from participating in the study