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Study to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia

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ClinicalTrials.gov Identifier: NCT01749540
Recruitment Status : Completed
First Posted : December 13, 2012
Last Update Posted : December 14, 2016
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Tracking Information
First Submitted Date  ICMJE December 10, 2012
First Posted Date  ICMJE December 13, 2012
Last Update Posted Date December 14, 2016
Study Start Date  ICMJE February 2013
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 26, 2013)
Proportion of patients who have an erythroid response. [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 12, 2012)
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. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 26, 2013)
  • 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. ]
  • ACE-536 pharmacokinetics. [ Time Frame: Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks. ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 12, 2012)
  • Number of patients with adverse events. [ Time Frame: From treatment initiation to End-of-Study visit (approximately 24 weeks later). ]
  • Change in hemoglobin. [ 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. ]
  • ACE-536 pharmacokinetics. [ Time Frame: Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks. ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Evaluate the Effects of ACE-536 in Patients With Beta-thalassemia
Official Title  ICMJE A Phase 2, Open-Label, Ascending Dose Study to Evaluate the Effects of ACE-536 in Patients With Beta-Thalassemia Intermedia
Brief Summary The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia.
Detailed 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE B-Thalassemia
Intervention  ICMJE Drug: ACE-536
Subjects receive ACE-536 administered subcutaneously (SC) every 3 weeks for up to 5 cycles.
Other Name: luspatercept
Study Arms  ICMJE Experimental: ACE 536
ACE-536 - 1 of 7 possible dose levels.
Intervention: Drug: ACE-536
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 13, 2015)
64
Original Estimated Enrollment  ICMJE
 (submitted: December 12, 2012)
50
Actual Study Completion Date  ICMJE November 2015
Actual Primary Completion Date November 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Greece,   Italy
Removed Location Countries Turkey
 
Administrative Information
NCT Number  ICMJE NCT01749540
Other Study ID Numbers  ICMJE A536-04
2012-002499-15 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP