Study of ACE-536 to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
First received: December 10, 2012
Last updated: October 8, 2015
Last verified: October 2015
The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase 2, Open-Label, Ascending Dose Study to Evaluate the Effects of ACE-536 in Patients With Beta-Thalassemia
Primary Outcome Measures:
- Proportion of patients who have an erythroid response. [ Time Frame: Assessed at approximately 24 weeks from patient screening. ] [ Designated as safety issue: No ]
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.
Secondary Outcome Measures:
- Number of patients with adverse events. [ Time Frame: From treatment initiation to End-of-Study visit (approximately 24 weeks later). ] [ Designated as safety issue: Yes ]
- Change in hemoglobin level in non-transfusion dependent patients. [ Time Frame: Baseline to approximately 24 weeks. ] [ Designated as safety issue: No ]
- Changes in biomarkers of erythropoiesis, hemolysis, iron metabolism and bone metabolism. [ Time Frame: Baseline to approximately 24 weeks. ] [ Designated as safety issue: No ]
- ACE-536 pharmacokinetics. [ Time Frame: Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks. ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||November 2015 (Final data collection date for primary outcome measure)
Experimental: ACE 536
ACE-536 - 1 of 7 possible dose levels.
Subjects receive ACE-536 administered subcutaneously (SC) every 3 weeks for up to 5 cycles.
Other Name: luspatercept
The study will evaluate the safety and tolerability of ACE-536 in beta-thalassemia patients with anemia and the ability of ACE-536 to generate an erythroid response in these patients. An erythroid response in this study is 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
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
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
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 x109/L or > 1,000 x109/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 56 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).
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01749540
|Laiko General Hospital, Ampelokipi
|Athens, Greece |
|ARNAS Garibaldi - P.O. Garibaldi Centro
|Catania, Italy |
|A.O.U. Arcispedale S. Anna
|Ferrara, Italy |
|A.O.U. Seconda Università degli Studi di Napoli
|Napoli, Italy |
|AORN A. Cardarelli
|Napoli, Italy |
|A.O.U. San Luigi Gonzaga
|Orbassano, Italy |
Acceleron Pharma, Inc.
No publications provided
||Acceleron Pharma, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 10, 2012
||October 8, 2015
||Italy: The Italian Medicines Agency
United States: Food and Drug Administration
Greece: Ministry of Health and Welfare
Turkey: Ministry of Health
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 09, 2015
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn