B-Thalassemia Clinical Trial
Official title:
A Phase 2, Open-Label, Ascending Dose Study to Evaluate the Effects of ACE-536 in Patients With Beta-Thalassemia Intermedia
The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia.
| Status | Completed |
| Enrollment | 64 |
| Est. completion date | November 2015 |
| Est. primary completion date | November 2015 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Key Inclusion Criteria: - Men or women >=18 years of age - For the dose escalation phase of the study: documented diagnosis of ß-thalassemia intermedia (transfusion dependent patients must not have begun regular transfusions at age < 4.0 years). For the expansion cohort: documented diagnosis of ß-thalassemia (including ß-thalassemia major or ß-thalassemia intermedia). - Prior splenectomy or spleen size < 18 cm in the longest diameter by abdominal ultrasound (dose escalation cohorts only). - Anemia, defined as: (i) 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 during the screening period [Day -28 to Day -1]) in non-transfusion dependent patients, defined as having received < 4 units of RBCs within 8 weeks prior to Cycle 1 Day 1, or (ii) transfusion dependent, defined as requiring = 4 units of RBCs every 8 weeks (confirmed over 6 months prior to Cycle 1 Day 1). - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN). - Serum creatinine = 1.5 x ULN. - Adequate pregnancy avoidance measures. - Patients are able to adhere to the study visit schedule, understand and comply with all protocol requirements. - Understand and able to provide written informed consent. Key Exclusion Criteria: - 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. - Folate deficiency. - Symptomatic splenomegaly. - Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV). - 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). - Ejection fraction < 50% by echocardiogram, MUGA or cardiac MRI. - Uncontrolled hypertension defined as systolic blood pressure (BP) = 150 mm Hg or diastolic BP = 95 mm Hg. - Heart failure class 3 or higher (New York Heart Association, NYHA). - QTc > 450 msec on screening ECG. - Platelet count < 100 x10(9)/L or > 1,000 x10(9)/L. - Proteinuria = Grade 2. - 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. - 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. - Transfusion event within 7 days prior to Cycle 1 Day 1. - Patients receiving or planning to receive hydroxyurea treatment. Patients must not have had hydroxyurea within 90 days of Cycle 1 Day 1. - Splenectomy within 56 days prior to Cycle 1 Day 1. - 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. - Iron chelation therapy initiated within 56 days prior to Cycle 1 Day 1. - 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). - Pregnant of lactating females. - History of severe allergic or anaphylactic reactions of hypersensitivity to recombinant proteins or excipients in the investigational drug. - Prior treatment with sotatercept (ACE-011) or ACE-536. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Greece | Laiko General Hospital, Ampelokipi | Athens | |
| Italy | Ospedale "A. Perriino" U.O Ematologia | Brindisi | |
| Italy | ARNAS Garibaldi - P.O. Garibaldi Centro | Catania | |
| Italy | A.O.U. Arcispedale S. Anna | Ferrara | |
| Italy | CEMEF Medicina 2 | Modena | |
| Italy | A.O.U. Seconda Università degli Studi di Napoli | Napoli | |
| Italy | AORN A. Cardarelli | Napoli | |
| Italy | A.O.U. San Luigi Gonzaga | Orbassano |
| Lead Sponsor | Collaborator |
|---|---|
| Acceleron Pharma, Inc. |
Greece, Italy,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Proportion of patients who have an erythroid response. | Proportion of patients who have an erythroid response, defined as a 1) a hemoglobin increase of = 1.5 g/dL from baseline for = 14 days (in the absence of red blood cell [RBC] transfusions) in non-transfusion dependent patients, or 2) = 20% reduction in RBC transfusion burden compared to pretreatment in transfusion dependent patients. | Assessed at approximately 24 weeks from patient screening. | No |
| Secondary | Number of patients with adverse events. | From treatment initiation to End-of-Study visit (approximately 24 weeks later). | Yes | |
| Secondary | Change in hemoglobin level in non-transfusion dependent patients. | Baseline to approximately 24 weeks. | No | |
| Secondary | Changes in biomarkers of erythropoiesis, hemolysis, iron metabolism and bone metabolism. | Baseline to approximately 24 weeks. | No | |
| Secondary | ACE-536 pharmacokinetics. | Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks. | No |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03591900 -
The Use of CGMS to Detect Alterations of Blood Glucose in Thalassemic Patients
|
N/A |