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Trial record 1 of 1 for:    NCT02268409
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ACE-536 Extension Study - Beta Thalassemia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier:
NCT02268409
First received: October 6, 2014
Last updated: December 14, 2016
Last verified: December 2016
  Purpose
Study A536-06 is an open-label extension study for patients previously enrolled in study A536-04 (ClinicalTrials.gov Identifier NCT01749540), to evaluate the long-term safety and tolerability of ACE-536 in adult patients with beta-thalassemia.

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Extension Study to Evaluate the Long-Term Effects of ACE-536 in Patients With β-Thalassemia Previously Enrolled in Study A536-04

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Long-term safety and tolerability of ACE-536 in patients with β thalassemia who were previously enrolled in study A536-04 [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
    safety and tolerability will be assessed by recording and classification of all adverse events (clinical and laboratory) reported by study investigators in all subjects who received at least one dose of study drug


Secondary Outcome Measures:
  • Erythroid response in non-transfusion dependent (NTD) patients [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
    Proportion of patients with a mean hemoglobin increase ≥ 1.5 g/dL over continuous 8-week interval compared to baseline, not influenced by red blood cell (RBC) transfusion

  • Erythroid response in non-transfusion dependent (NTD) patients [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
    Proportion of patients with a mean hemoglobin increase ≥ 1.5 g/dL over continuous 12-week interval compared to baseline, not influenced by red blood cell (RBC) transfusion

  • Erythroid response in transfusion dependent (TD) patients [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
    Proportion of patients with a reduction in RBC transfusion burden by ≥ 20% over a continuous 8-week interval compared to the 8 weeks prior to the start of treatment

  • Erythroid response in transfusion dependent (TD) patients [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
    Proportion of patients with a reduction in RBC transfusion burden by ≥ 50% over a continuous 12-week interval compared to the 12 weeks prior to the start of treatment

  • Time to, and duration of, erythroid response [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
  • Mean change from baseline in hemoglobin levels in NTD patients not influenced by RBC transfusion [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730 ]
  • Mean % change from baseline in transfusion burden in TD patients [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
  • Mean change in pre-transfusion hemoglobin levels in TD patients [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
  • Changes in markers of erythropoiesis [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
  • Changes in markers of iron metabolism [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
  • ACE-536 pharmacokinetic profile - Cmax, Tmax and area under the plasma concentration versus time curve (AUC) [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]
  • Quality of Life assessments (exploratory) [ Time Frame: From first dose (Study Day 1) to end of treatment (Study Day 730) ]

Estimated Enrollment: 64
Study Start Date: November 2014
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACE-536 0.8 mg/kg once every 3 weeks SC
ACE-536 0.8 mg/kg once every 3 weeks by SC injection
Drug: ACE-536
ACE-536 0.8 mg/kg once every 3 weeks by SC injection
Other Name: luspatercept

Detailed Description:
Study A536-06 is an open-label extension study for patients previously enrolled in study A536-04 (ClinicalTrials.gov Identifier NCT01749540), to evaluate the safety,tolerability and pharmacodynamic effects of up to 24 months of ACE-536 treatment in adult patients with beta-thalassemia previously treated with ACE-536 for up to 3 months in study A536-04. The starting dose level in A536-06 will be 0.8 mg/kg by subcutaneous (SC) injection once every 3 weeks. Dose titration/modification rules will be followed for individual patients and will be based upon safety and efficacy data collected during the course of treatment.
  Eligibility

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

Inclusion Criteria:

  1. Completion of the treatment period in the base study A536-04.
  2. 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 and for 12 weeks following the last dose of ACE-536. Males must agree to use a latex condom during any sexual contact with females of child-bearing potential during study participation 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.
  3. Patient is able to adhere to the study visit schedule, understand and comply with all protocol requirements.
  4. Patient understands and is able to provide written informed consent

    Patients with treatment interruption (defined as patients who complete the EOS visit for study A536-04 and are ≥ 28 days post EOS visit) must also meet the following criteria

  5. Mean hemoglobin concentration < 10.0 g/dL of 2 measurements (not influenced by RBC transfusion) (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 NTD patients.
  6. Adequate folate levels or on folate therapy.
  7. Platelet count ≥ 100 x 10(9) /L and ≤ 1,000 x 10(9) /L.
  8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN).
  9. Serum creatinine ≤ 1.5 x ULN.
  10. Ejection fraction ≥ 50% by Echocardiogram (ECHO) or Multi gated acquisition scan (MUGA).

Exclusion Criteria:

  1. Discontinuation/withdrawal from study A536-04 due to patient request, patient unwillingness or inability to comply with the protocol, pregnancy, use of prohibited medication (e.g., hydroxyurea), medical reason or AE, hypersensitivity reaction to the study drug, at the discretion of the sponsor, or loss to follow-up prior to completion of the treatment period.
  2. 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.
  3. Symptomatic splenomegaly.
  4. Splenectomy within 56 days prior to Cycle 1 Day 1.
  5. 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.
  6. Patients receiving or planning to receive hydroxyurea treatment. Patients must not have had hydroxyurea within 90 days of Cycle 1 Day 1.
  7. For patients with treatment interruption: Iron chelation therapy if initiated within 56 days prior to Cycle 1 Day 1.
  8. 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/day and low molecular weight (LMW) heparin for superficial vein thrombosis (SVT) is permitted).
  9. Treatment with another investigational drug (including sotatercept [ACE-011]) 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 at any time between the end of treatment of the base study A536-04 and Cycle 1 Day 1.
  10. Known positive for human immunodeficiency virus (HIV), active infectious hepatitis B (HBV) or active infectious hepatitis C (HCV).
  11. Uncontrolled hypertension defined as systolic blood pressure (SBP) ≥ 150 mm Hg or diastolic blood pressure (DBP) ≥ 100 mm Hg.
  12. 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).
  13. Pregnant or lactating females.
  14. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational drug.
  15. Any other condition not specifically noted above which, in the judgment of the investigator, would preclude the patient from participating in the study.
  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: NCT02268409

Locations
Greece
Acceleron Investigative Site
Athens, Greece
Italy
Acceleron Investigative Site
Brindisi, Italy
Acceleron Investigative Site
Catania, Italy
Acceleron Investigative Site
Ferrara, Italy
Acceleron Investigative Site
Modena, Italy
Acceleron Investigative Site
Naples, Italy
Acceleron Investigative Site
Turin, Italy
Sponsors and Collaborators
Acceleron Pharma, Inc.
  More Information

Responsible Party: Acceleron Pharma, Inc.
ClinicalTrials.gov Identifier: NCT02268409     History of Changes
Other Study ID Numbers: A536-06
Study First Received: October 6, 2014
Last Updated: December 14, 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