ß-thalassemia intermedia MedDRA version: 15.1 Level: LLT Classification code 10062923 Term: Thalassemia intermedia System Organ Class: 100000004850 MedDRA version: 15.1 Level: LLT Classification code 10054660 Term: Thalassemia beta System Organ Class: 100000004850
Conditions
Interventions
Product Name: NA
Product Code: ACE-536
Pharmaceutical Form: Injection
CAS Number: 1373715-00-4
Current Sponsor code: ACE-536
Other descriptive name: Modified ActRIIB receptor - IgG1 Fc fusion protein
Sponsors
ACCELERON PHARMA INC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women 18 years of age. 2. Documented diagnosis of ß-thalassemia intermedia, with anemia requiring no more than 6 transfusion events in the last year, with no transfusion events for 56 days prior to Cycle 1 Day 1 3. Prior splenectomy or spleen size =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any clinically significant pulmonary (including pulmonary hypertension), cardiovascular, endocrine, neurologic, hepatic, gastrointestinal, infectious or genitourinary disease considered by the investigator as not adequately controlled prior to Cycle 1 Day 1. 2. Folate deficiency. 3. Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B(HBV) or active infectious hepatitis C (HCV). 4. 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). 5. Ejection fraction 450 msec on screening ECG. 9. Platelet count 1,000,000 x109/L. 10. Proteinuria = Grade 2. 11. Any active infection requiring parenteral antibiotic therapy within 28 days prior to Cycle 1 Day 1 or oral antibiotics within 14 days of Cycle 1 Day 1. 12. Treatment with another investigational drug 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. 13. Patients receiving or planning to receive hydroxyurea treatment. Patients must not have had hydroxyurea within 56 days of Cycle 1 Day 1. 14. Splenectomy with 56 days prior to Cycle 1 Day 1. 15. 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. 16. Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1 17. Cytotoxic agents, systemic corticosteroids, immunosuppressants, or anticoagulant therapy such as warfarin or heparin within 28 days priorto Cycle 1 Day 1 (prophylactic aspirin up to 100 mg/d is permitted). 18. Pregnant or lactating females. 19. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of ACE-536 on the proportion of patients who have an erythroid response, defined as a hemoglobin increase of = 1.5 g/dL from baseline for = 14 days (in the absence of transfusion) in patients with ß-thalassemia intermedi;Secondary Objective: To evaluate i)safety and tolerability of ACE-536,(ii)change in hemoglobin level compared to baseline + time and duration of erythroid response(iii)changes in biomarkers of erythropoiesis(iv)pharmacokinetics profile;Primary end point(s): The primary efficacy endpoint is erythroid response, defined as the proportion of patients who have a hemoglobin increase of = 1.5 g/dL from baseline for = 14 days, in the absence of transfusion. The erythroid response will be summarized using both a point estimate and its exact 95% confidence interval based on binomial distribution. The primary efficacy analysis will be performed using the EE population.;Timepoint(s) of evaluation of this end point: 20 weeks following initiation of treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints will be assessed by examining other hematology, erythropoiesis, iron metabolism, and bone metabolism parameters, as well as MRI scan for liver iron content (LIC). - Erythropoiesis parameters include serum erythropoietin levels, hemoglobin analysis (electrophoresis, globin chain RNA), reticulocytes, and nucleated RBCs - Hemolysis parameters include haptoglobin, indirect bilirubin, and lactate dehydrogenase (LDH) - Iron metabolism parameters include serum iron, total iron binding capacity (TIBC), transferrin, soluble transferrin receptor, ferritin, non-transferrin bound iron (NTBI), hepcidin, and liver iron content (LIC) by MRI - Bone metabolism parameters include bone specific alkaline phosphatase (BSAP) and C-telopeptide of type I collagen (CTX) Exploratory endpoints will include evaluation of biomarkers related to the TGF Beta superfamily.;Timepoint(s) of evaluation of this end point: 20 weeks following initiation of treatment | — |
Countries
Greece, Italy
Contacts
Public ContactKenneth Attie
Acceleron Pharma, Inc
Outcome results
None listed