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

Sponsor
Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.) (Industry)
Overall Status
Completed
CT.gov ID
NCT01749540
Collaborator
(none)
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Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
64 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (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
Study Start Date :
Feb 1, 2013
Actual Primary Completion Date :
Nov 1, 2015
Actual Study Completion Date :
Nov 1, 2015

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • luspatercept
  • Outcome Measures

    Primary Outcome Measures

    1. Proportion of patients who have an erythroid response. [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

    1. Number of patients with adverse events. [From treatment initiation to End-of-Study visit (approximately 24 weeks later).]

    2. Change in hemoglobin level in non-transfusion dependent patients. [Baseline to approximately 24 weeks.]

    3. Changes in biomarkers of erythropoiesis, hemolysis, iron metabolism and bone metabolism. [Baseline to approximately 24 weeks.]

    4. ACE-536 pharmacokinetics. [Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks.]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Laiko General Hospital, Ampelokipi Athens Greece
    2 Ospedale "A. Perriino" U.O Ematologia Brindisi Italy
    3 ARNAS Garibaldi - P.O. Garibaldi Centro Catania Italy
    4 A.O.U. Arcispedale S. Anna Ferrara Italy
    5 CEMEF Medicina 2 Modena Italy
    6 A.O.U. Seconda Università degli Studi di Napoli Napoli Italy
    7 AORN A. Cardarelli Napoli Italy
    8 A.O.U. San Luigi Gonzaga Orbassano Italy

    Sponsors and Collaborators

    • Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
    ClinicalTrials.gov Identifier:
    NCT01749540
    Other Study ID Numbers:
    • A536-04
    • 2012-002499-15
    First Posted:
    Dec 13, 2012
    Last Update Posted:
    Dec 14, 2016
    Last Verified:
    Dec 1, 2016
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 14, 2016