ACE-536 Extension Study - Beta Thalassemia

This is an interventional treatment trial for Beta-Thalassemia Read More

Inclusion Criteria:

1. Completion of the treatment period in the base study A536-04.
2. Females of child bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation and for 12 weeks following the last dose of ACE-536. Males must agree to use a latex condom during any sexual contact with females of child-bearing potential during study participation and for 12 weeks following the last dose of ACE-536, even if he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of ACE-536.
3. Patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements.

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

   Patients with treatment interruption (defined as patients who complete the EOS visit for study A536-04 and are ≥ 28 days post EOS visit) must also meet the following criteria

5. Mean hemoglobin concentration < 10.0 g/dL of 2 measurements (not influenced by RBC transfusion) (one performed within one day prior to Cycle 1 Day 1 and the other performed during the screening period [Day -28 to Day -1]) in NTD patients.
6. Adequate folate levels or on folate therapy.
7. Platelet count ≥ 100 x 10(9) /L and ≤ 1,000 x 10(9) /L.
8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN).
9. Serum creatinine ≤ 1.5 x ULN.
10. Ejection fraction ≥ 50% by Echocardiogram (ECHO) or Multi gated acquisition scan (MUGA).

Exclusion Criteria:

1. Discontinuation/withdrawal from study A536-04 due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication (e.g., hydroxyurea), medical reason or 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.
2. Any clinically significant pulmonary (including pulmonary hypertension), cardiovascular, endocrine, neurologic, hepatic, gastrointestinal, infectious, immunological (including clinically significant allo- or auto-immunization) or genitourinary disease considered by the investigator as not adequately controlled prior to Cycle 1 Day 1.
3. Symptomatic splenomegaly.
4. Splenectomy within 56 days prior to Cycle 1 Day 1.
5. Major surgery (except splenectomy) within 28 days prior to Cycle 1 Day 1. Patients must have completely recovered from any previous surgery prior to Cycle 1 Day 1.
6. Patients receiving or planning to receive hydroxyurea treatment. Patients must not have had hydroxyurea within 90 days of Cycle 1 Day 1.
7. For patients with treatment interruption: Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1.
8. Cytotoxic agents, systemic corticosteroids, immunosuppressants, or anticoagulant therapy such as warfarin or heparin within 28 days prior to Cycle 1 Day 1 (prophylactic aspirin up to 100 mg/day and low molecular weight (LMW) heparin for superficial vein thrombosis (SVT) is permitted).
9. 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 at any time between the end of treatment of the base study A536-04 and Cycle 1 Day 1.
10. Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV).
11. Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 150 mm Hg or diastolic blood pressure (DBP) ≥ 100 mm Hg.
12. Known history of thromboembolic events ≥ grade 3 according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.4.0 (current active minor version).
13. Pregnant or lactating females.
14. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug.
15. Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study.