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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Acceleron Pharma, Inc.
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT01749540
First received: December 10, 2012
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to evaluate the effects of ACE-536 in patients with beta-thalassemia.


Condition Intervention Phase
Beta-thalassemia.
Drug: ACE-536
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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

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. ] [ 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: 50
Study Start Date: January 2013
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: December 2014 (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:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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, 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).
  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

Contacts
Contact: Clinical Trials Manager 617-649-9200 clinicaltrials536@acceleronpharma.com

Locations
Greece
Acceleron Investigative Site Recruiting
Athens, Greece
Italy
Acceleron Investigative Site Recruiting
Turin, Italy
Turkey
Acceleron Investigative Site Not yet recruiting
Ankara, Turkey
Sponsors and Collaborators
Acceleron Pharma, Inc.
  More Information

No publications provided

Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT01749540     History of Changes
Other Study ID Numbers: A536-04
Study First Received: December 10, 2012
Last Updated: August 18, 2014
Health Authority: Italy: Agenzia Italiana del Farmaco (AIFA)

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 September 18, 2014