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Summary

for people ages 18 years and up (full criteria)
at Oakland, California and other locations
study started
estimated completion:

Description

Summary

This is a Phase 3, double-blind, randomized, placebo-controlled, multicenter study to determine the efficacy and safety of luspatercept (ACE-536) plus Best supportive care (BSC) versus placebo plus BSC in adults who require regular red blood cell transfusion due to (β)-thalassemia. The study is divided into the Screening/Run-in Period, double-blind Treatment Period, double-blind Long-term Treatment Period, and Post-treatment Follow-up Period.

Official Title

A Phase 3, Double-Blind, Placebo Controlled Multicenter Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) in Adults With Transfusion Dependent Beta (B)-Thalassemia

Keywords

Erythrocyte Transfusion Beta-Thalassemia ACE-536 Safety Efficacy Placebo Red Blood Cell Transfusions Beta -Thalassemia

Eligibility

You can join if…

Open to people ages 18 years and up

  • Subjects must satisfy the following criteria to be enrolled in the study:

    1. Male or female, ≥ 18 years of age at the time of signing the informed consent document (ICF).
    2. Subject must understand and voluntarily sign an Inform Consent Form prior to any study-related assessments/procedures being conducted.
    3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
    4. Documented diagnosis of β-thalassemia or Hemoglobin E/β-thalassemia.
    5. Regularly transfused, defined as: 6-20 Red Blood Cell (RBC) units in the 24 weeks prior to randomization and no transfusion-free period for ≥ 35 days during that period.
    6. Performance status: Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
    7. A female of childbearing potential (FCBP) for this study is defined as a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). FCBP participating in the study must:
  • Have two negative pregnancy tests as verified by the Investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
  • Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with,effective contraception without interruption, 28 days prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks (approximately five times the mean terminal half-life of luspatercept based on multiple-dose Pharmacokinetic PK) data) after discontinuation of study therapy.

    1. Male subjects must:
  • Practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 12 weeks (approximately five times the mean terminal half-life of luspatercept based on multiple-dose PK data) following investigational product discontinuation, even if he has undergone a successful vasectomy.

You CAN'T join if...

  • The presence of any of the following will exclude a subject from enrollment:

    1. Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
    2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
    3. Any condition that confounds the ability to interpret data from the study.
    4. A diagnosis of Hemoglobin S/β-thalassemia or alpha (α)-thalassemia (eg, Hemoglobin H);β-thalassemia combined with α-thalassemia is allowed.
    5. Evidence of active hepatitis C (HCV) infection, or active infectious hepatitis B, or known positive human immunodeficiency virus (HIV).
    6. Deep Vein Thrombosis (DVT) or stroke requiring medical intervention ≤ 24 weeks prior to randomization.
    7. Chronic anticoagulant therapy ≤ 28 days prior to randomization, Low Molecular Weight(LMW) heparin for Sinus venous Thrombosis (SVT) and chronic aspirin are allowed.
    8. Platelet count> 1000 x 109/L
    9. Insulin-dependent diabetes, ie, chronic treatment with insulin.
    10. Treatment with another investigational drug or device ≤ 28 days prior to randomization.
    11. Prior exposure to sotatercept (ACE-011) or luspatercept (ACE-536).
    12. Use of an erythropoiesis-stimulating agent (ESA) ≤ 24 weeks prior to randomization.
    13. Iron chelation therapy, if initiated ≤ 24 weeks prior to randomization (allowed if initiated> 24 weeks before or during treatment).
    14. Hydroxyurea treatment ≤ 24 weeks prior to randomization.
    15. Pregnant or lactating females.
    16. Uncontrolled hypertension. Controlled hypertension for this protocol is considered ≤Grade 1 according to NCI Common Terminology Criteria for Adverse Events (CTCAE)version 4.0 (current active minor version).
    17. Major organ damage, including:
  • Liver disease with alanine aminotransferase (ALT)> 3 x the upper limit of normal(ULN) or histopathological evidence of liver cirrhosis/fibrosis on liver biopsy;
  • Heart disease, heart failure as classified by the New York Heart Association(NYHA) classification 3 or higher, or significant arrhythmia requiring treatment,or recent myocardial infarction within 6 months of randomization.
  • Lung disease, including pulmonary fibrosis or pulmonary hypertension which are clinically significant.
  • Creatinine clearance < 60 mL/min (per Cockroff-Gault method).

    1. Proteinuria ≥ Grade 3 according to NCI CTCAE version 4.0 (current active minor version).
    2. Adrenal insufficiency.
    3. Major surgery ≤ 12 weeks prior to randomization (subjects must have completely recovered from any previous surgery prior to randomization).
    4. History of severe allergic or anaphylactic reactions or hypersensitivity to recombinant proteins or excipients in the investigational product (see Investigator Brochure).
    5. Cytotoxic agents, immunosuppressants ≤ 28 days prior to randomization.

Locations

  • Children's Hospital of Los Angeles
    Los Angeles, California, 90027, United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Celgene
ID
NCT02604433
Phase
Phase 3
Study Type
Interventional
Last Updated
July 1, 2017