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

A Phase 2, Open-Label, Ascending Dose Study to Evaluate the Effects of ACE-536 in Patients With Beta-Thalassemia Intermedia

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

64

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Athens, Greece
        • Laiko General Hospital, Ampelokipi
      • Brindisi, Italy
        • Ospedale "A. Perriino" U.O Ematologia
      • Catania, Italy
        • ARNAS Garibaldi - P.O. Garibaldi Centro
      • Ferrara, Italy
        • A.O.U. Arcispedale S. Anna
      • Modena, Italy
        • CEMEF Medicina 2
      • Napoli, Italy
        • AORN A. Cardarelli
      • Napoli, Italy
        • A.O.U. Seconda Università degli Studi di Napoli
      • Orbassano, Italy
        • A.O.U. San Luigi Gonzaga

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ACE 536
ACE-536 - 1 of 7 possible dose levels.
Subjects receive ACE-536 administered subcutaneously (SC) every 3 weeks for up to 5 cycles.
Other Names:
  • luspatercept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Assessed at approximately 24 weeks from patient screening.

Secondary Outcome Measures

Outcome Measure
Time Frame
Number of patients with adverse events.
Time Frame: From treatment initiation to End-of-Study visit (approximately 24 weeks later).
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.
Baseline to approximately 24 weeks.
Changes in biomarkers of erythropoiesis, hemolysis, iron metabolism and bone metabolism.
Time Frame: Baseline to approximately 24 weeks.
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.
Measured at multiple time points over the course of treatment, from study day 1 to approximately 24 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

November 1, 2015

Study Registration Dates

First Submitted

December 10, 2012

First Submitted That Met QC Criteria

December 12, 2012

First Posted (Estimate)

December 13, 2012

Study Record Updates

Last Update Posted (Estimate)

December 14, 2016

Last Update Submitted That Met QC Criteria

December 13, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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