Study of ACE-536 to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia Intermedia
This study is currently recruiting participants.
Verified March 2013 by Acceleron Pharma, Inc.
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
First received: December 10, 2012
Last updated: March 14, 2013
Last verified: March 2013
The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia intermedia.
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 Intermedia
Primary Outcome Measures:
- Proportion of patients who have an erythroid response, defined as a hemoglobin increase of ≥ 1.5 g/dL from baseline for ≥ 14 days (in the absence of transfusion). [ Time Frame: Assessed at approximately 24 weeks from patient screening. ] [ Designated as safety issue: No ]
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. [ 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:
||July 2014 (Final data collection date for primary outcome measure)
Experimental: ACE 536
ACE-536 - 1 of 5 possible dose levels.
Subjects receive ACE-536 administered subcutaneously (SC) every 3 weeks for up to 5 cycles.
The study will evaluate the safety and tolerability of ACE-536 in beta-thalassemia intermedia patients with anemia and the ability of ACE-536 to generate an erythroid response in these patients. Eligible patients may have received up to 6 red blood cell transfusions during the previous 12 months (with none during the 8-week period prior to study enrollment). An erythroid response in this study is defined as an increase in hemoglobin of at least 1.5 g/dL from pretreatment baseline values, sustained for at least 14 days, in the absence of a red blood cell transfusion.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
Key Inclusion Criteria:
- Documented diagnosis of beta-thalassemia intermedia, with anemia requiring at least 1, but no more than 6 transfusion events in the last year, with no transfusion events for 56 days prior to Cycle 1 Day 1.
- Prior splenectomy or spleen size < 18 cm in the longest diameter by abdominal ultrasound.
- 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 7-28 days prior, not influenced by RBC transfusion within 7 days of measurement).
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN).
- Serum creatinine ≤ 1.5 x ULN.
- Females of child bearing potential (defined as sexually mature women who have not undergone hysterectomy or bilateral oophorectomy, or are not naturally postmenopausal ≥ 24 consecutive months) must have negative urine or blood pregnancy test prior to enrollment and use adequate birth control methods (abstinence, oral contraceptives, barrier method with spermicide, or surgical sterilization) during study participation. Males must agree to use a latex condom during any sexual contact with females of child-bearing potential while participating in the study and for 12 weeks following the last dose of ACE 536, even if he has undergone a successful vasectomy. Patients must be counseled concerning measures to be used to prevent pregnancy and potential toxicities prior to the first dose of ACE-536.
Key Exclusion Criteria:
- Any clinically significant pulmonary (including pulmonary hypertension), cardiovascular, endocrine, neurologic, hepatic, gastrointestinal, infectious or genitourinary disease considered by the investigator as not adequately controlled prior to Cycle 1 Day 1.
- Folate deficiency.
- 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, Appendix 1).
- QTc > 450 msec on screening ECG.
- Platelet count < 100 x109/L or > 1,000,000 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.
- Patients receiving or planning to receive hydroxyurea treatment. Patients must not have had hydroxyurea within 56 days of Cycle 1 Day 1.
- Splenectomy with 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 if 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 or lactating females.
- History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01749540
|Acceleron Investigative Site
|Turin, Italy |
Acceleron Pharma, Inc.
No publications provided
||Acceleron Pharma, Inc.
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 10, 2012
||March 14, 2013
||Italy: Agenzia Italiana del Farmaco (AIFA)
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 16, 2013
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn