Study to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Detailed Description
To evaluate the proportion of β-thalassemia patients who have an erythroid response, defined as:
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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
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≥ 20% reduction in RBC transfusion burden compared to pretreatment in transfusion dependent patients.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: ACE 536 ACE-536 - 1 of 7 possible dose levels. |
Drug: ACE-536
Subjects receive ACE-536 administered subcutaneously (SC) every 3 weeks for up to 5 cycles.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Proportion of patients who have an erythroid response. [Assessed at approximately 24 weeks from patient screening.]
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. [From treatment initiation to End-of-Study visit (approximately 24 weeks later).]
- Change in hemoglobin level in non-transfusion dependent patients. [Baseline to approximately 24 weeks.]
- Changes in biomarkers of erythropoiesis, hemolysis, iron metabolism and bone metabolism. [Baseline to approximately 24 weeks.]
- ACE-536 pharmacokinetics. [Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks.]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Men or women >=18 years of age
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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).
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Prior splenectomy or spleen size < 18 cm in the longest diameter by abdominal ultrasound (dose escalation cohorts only).
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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).
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Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN).
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Serum creatinine ≤ 1.5 x ULN.
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Adequate pregnancy avoidance measures.
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Patients are able to adhere to the study visit schedule, understand and comply with all protocol requirements.
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Understand and able to provide written informed consent.
Key Exclusion Criteria:
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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.
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Folate deficiency.
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Symptomatic splenomegaly.
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Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV).
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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).
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Ejection fraction < 50% by echocardiogram, MUGA or cardiac MRI.
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Uncontrolled hypertension defined as systolic blood pressure (BP) ≥ 150 mm Hg or diastolic BP ≥ 95 mm Hg.
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Heart failure class 3 or higher (New York Heart Association, NYHA).
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QTc > 450 msec on screening ECG.
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Platelet count < 100 x10(9)/L or > 1,000 x10(9)/L.
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Proteinuria ≥ Grade 2.
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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.
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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.
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Transfusion event within 7 days prior to Cycle 1 Day 1.
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Patients receiving or planning to receive hydroxyurea treatment. Patients must not have had hydroxyurea within 90 days of Cycle 1 Day 1.
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Splenectomy within 56 days prior to Cycle 1 Day 1.
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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.
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Iron chelation therapy initiated within 56 days prior to Cycle 1 Day 1.
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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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Pregnant of lactating females.
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History of severe allergic or anaphylactic reactions of hypersensitivity to recombinant proteins or excipients in the investigational drug.
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Prior treatment with sotatercept (ACE-011) or ACE-536.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Laiko General Hospital, Ampelokipi | Athens | Greece | ||
2 | Ospedale "A. Perriino" U.O Ematologia | Brindisi | Italy | ||
3 | ARNAS Garibaldi - P.O. Garibaldi Centro | Catania | Italy | ||
4 | A.O.U. Arcispedale S. Anna | Ferrara | Italy | ||
5 | CEMEF Medicina 2 | Modena | Italy | ||
6 | A.O.U. Seconda Università degli Studi di Napoli | Napoli | Italy | ||
7 | AORN A. Cardarelli | Napoli | Italy | ||
8 | A.O.U. San Luigi Gonzaga | Orbassano | Italy |
Sponsors and Collaborators
- Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- A536-04
- 2012-002499-15