Study to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia
This trial has been completed.
|Sponsor||Acceleron Pharma, Inc.|
|Start date||February 2013|
|End date||November 2015|
|Trial size||64 participants|
|Trial identifier||NCT01749540, A536-04|
The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia.
|United States||No locations recruiting|
|Other countries||No locations recruiting|
|Athens, Greece||Laiko General Hospital, Ampelokipi||completed|
|Brindisi, Italy||Ospedale "A. Perriino" U.O Ematologia||completed|
|Catania, Italy||ARNAS Garibaldi - P.O. Garibaldi Centro||completed|
|Ferrara, Italy||A.O.U. Arcispedale S. Anna||completed|
|Modena, Italy||CEMEF Medicina 2||completed|
|Napoli, Italy||A.O.U. Seconda Università degli Studi di Napoli||completed|
|Napoli, Italy||AORN A. Cardarelli||completed|
|Orbassano, Italy||A.O.U. San Luigi Gonzaga||completed|
|Endpoint classification||safety/efficacy study|
|Intervention model||single group assignment|
ACE-536 - 1 of 7 possible dose levels.
Proportion of patients who have an erythroid response.
time frame: Assessed at approximately 24 weeks from patient screening.
Number of patients with adverse events.
time frame: From treatment initiation to End-of-Study visit (approximately 24 weeks later).
Change in hemoglobin level in non-transfusion dependent patients.
time frame: Baseline to approximately 24 weeks.
Changes in biomarkers of erythropoiesis, hemolysis, iron metabolism and bone metabolism.
time frame: Baseline to approximately 24 weeks.
time frame: Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks.
Male or female participants at least 18 years old.
Key Inclusion Criteria: - Men or women >=18 years of age - For the dose escalation phase of the study: documented diagnosis of β-thalassemia intermedia (transfusion dependent patients must not have begun regular transfusions at age < 4.0 years). For the expansion cohort: documented diagnosis of β-thalassemia (including β-thalassemia major or β-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.
|Official title||A Phase 2, Open-Label, Ascending Dose Study to Evaluate the Effects of ACE-536 in Patients With Beta-Thalassemia Intermedia|
|Description||To evaluate the proportion of β-thalassemia patients who have an erythroid response, defined as: 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.|
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