ß-Thalassemia Intermedia and ß-Thalassemia major MedDRA version: 17.0 Level: LLT Classification code 10062923 Term: Thalassemia intermedia System Organ Class: 100000004850 MedDRA version: 17.0 Level: LLT Classification code 10054661 Term: Thalassemia major System Organ Class: 100000004850 MedDRA version: 17.0 Level: LLT Classification code 10054660 Term: Thalassemia beta System Organ Class: 100000004850
Conditions
Sponsors
Acceleron Pharma, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All patients must meet the following 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 while participating in the study 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 =65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: All patients must not meet any of the following 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. 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/d 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the long-term safety and tolerability of ACE-536 in patients with ß-thalassemia who were previously enrolled in study A536-04.;Primary end point(s): The primary efficacy endpoint is to evaluate the long-term safety and tolerability of ACE-536 in patients with ß-thalassemia who were previously enrolled in study A536-04. ;Timepoint(s) of evaluation of this end point: End of Study;Secondary Objective: To evaluate - erythroid response - the time to erythroid response and duration of erythroid response - the mean change from baseline over an 8- or 12-week period in hemoglobin level in NTD patients not influenced by RBC transfusion -mean % change from baseline in transfusion burden over an 8- or 12-week period in TD patients. - mean change in pre-transfusion hemoglobin levels in TD patients -changes in markers of erythropoiesis, hemolysis, iron overload, and iron metabolism -To examine the pharmacokinetic (PK) profile of ACE-536 in patients with ß-thalassemia Exploratory:To evaluate - biomarkers related to the (TGF-ß) superfamily - patient self-reported quality of life using the FACT-An and SF-36 questionnaires - change in extramedullary hematopoiesis (EMH) mass size - change in spleen size - change in leg ulcers | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -To Evaluate erythroid response defined as the proportion of patients with: o Mean hemoglobin increase = 1.5 g/dL over a continuous 12-week interval compared to baseline in non-transfusion dependent (NTD) patients, not influenced by RBC transfusion, OR o Reduction in RBC transfusion burden by = 50% over a continuous 12-week interval compared to the 12 weeks prior to the start of treatment in transfusion dependent (TD) patients. -To evaluate erythroid response defined as proportion of patients with: o Mean hemoglobin increase = 1.5 g/dL over a continuous 8-week interval compared to baseline in NTD patients, not influenced by RBC transfusion, OR o Reduction in RBC transfusion burden by = 20% over a continuous 8-week interval compared to the 8 weeks prior to the start of treatment in TD patients. To evaluate: - Time to erythroid response and duration of erythroid response - Mean change from baseline over an 8- or 12-week period in hemoglobin level in NTD patients not influenced by RBC transfusion - Mean % change from baseline in transfusion burden over an 8- or 12-week period in TD patients - Mean change in pre-transfusion hemoglobin levels in TD patients - Changes in markers of erythropoiesis, hemolysis, iron overload, and iron metabolism - PK profile of ACE-536 in patients with ß-thalassemia Exploratory endpoints will include evaluation of biomarkers related to the TGF Beta superfamily and evaluation of self-reported quality of life using the FACT--An and SF-36 questionnaires and to evaluate change in; extramedullary hematopoiesis (EMH) mass size, change in spleen size, change in leg ulcers.;Timepoint(s) of evaluation of this end point: End of Study | — |
Countries
Greece, Italy, Turkey
Contacts
Public ContactKenneth Attie
Acceleron Pharma, Inc.
Outcome results
None listed