Study of ACE-536 to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia
Verified March 2015 by Acceleron Pharma, Inc.
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
First received: December 10, 2012
Last updated: March 4, 2015
Last verified: March 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).
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749540
|Laiko General Hospital, Ampelokipi
|Athens, Greece |
|Contact +30 213 2060940 |
|ARNAS Garibaldi - P.O. Garibaldi Centro
|Catania, Italy |
|Contact +39 095 7593929 |
|A.O.U. Arcispedale S. Anna
|Ferrara, Italy |
|Contact +39 0532 237349 |
|A.O.U. Seconda Università degli Studi di Napoli
|Napoli, Italy |
|Contact +39 081 747 2708 |
|AORN A. Cardarelli
|Napoli, Italy |
|Contact +39 081 5665421 |
|A.O.U. San Luigi Gonzaga
|Orbassano, Italy |
|Contact +39 011 9026 032 |
|Bornova-Izmir, Turkey |
|Contact +90 532 3962746 |
Acceleron Pharma, Inc.
No publications provided
||Acceleron Pharma, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 10, 2012
||March 4, 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 July 27, 2015
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn