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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01749540
First received: December 10, 2012
Last updated: December 13, 2016
Last verified: December 2016
  Purpose
The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia.

Condition Intervention Phase
B-Thalassemia Drug: ACE-536 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 2, Open-Label, Ascending Dose Study to Evaluate the Effects of ACE-536 in Patients With Beta-Thalassemia Intermedia

Resource links provided by NLM:


Further study details as provided by Acceleron Pharma, Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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. ]

Enrollment: 64
Study Start Date: February 2013
Study Completion Date: November 2015
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: luspatercept

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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

Locations
Greece
Laiko General Hospital, Ampelokipi
Athens, Greece
Italy
Ospedale "A. Perriino" U.O Ematologia
Brindisi, Italy
ARNAS Garibaldi - P.O. Garibaldi Centro
Catania, Italy
A.O.U. Arcispedale S. Anna
Ferrara, Italy
CEMEF Medicina 2
Modena, 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
Sponsors and Collaborators
Acceleron Pharma, Inc.
  More Information

Additional Information:
Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01749540     History of Changes
Other Study ID Numbers: A536-04
2012-002499-15 ( EudraCT Number )
Study First Received: December 10, 2012
Last Updated: December 13, 2016

Additional relevant MeSH terms:
Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on June 23, 2017