AGT4HB: Gene Therapy for Hemophilia B

Dose-Escalation Study of a Self-Complementary Adeno-Associated Viral Vector for Gene Transfer in Hemophilia B

Categories:

Hematological Disorders

Phase I/II

Diseases Treated:

Hemophilia

Eligibility Overview:

  • 18 years old or older
  • Diagnosis of severe hemophilia B
  • Male
  • Treated/exposed to FIX products (e.g., concentrates or fresh, frozen plasma) for at least 10 years or 50 exposure days
  • At least 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes
  • Currently free of inhibitor and no history of inhibitors to FIX protein
  • Negative family history for development of an inhibitor
  1. Brief Summary

    Hemophilia is an excellent target for gene therapy. Even a small rise in circulating clotting factor could transform the lives of patients with severe hemophilia. Continuous synthesis of FIX by the host cells after gene therapy provides a real opportunity to prevent bleeding episodes rather than to treat bleeds after they have occurred. Additionally, successful gene therapy could avoid the risks and the inconvenience of regular infusion of clotting factor concentrates.

    This open-label, dose-escalation, Phase I/II study is designed to evaluate the safety and potential efficacy of a single bolus infusion of scAAV2/8-LP1-hFIXco into the peripheral vein of patients with severe hemophilia B. The vector is produced at the GMP Manufacturing Facility on the campus of St. Jude Children’s Research Hospital. Our modified vector design restricts expression to the liver, while enabling packaging of self-complementary genomes in a single capsid. This feature significantly improves the potency of AAV without compromising safety.

    Primary Objective

    • The primary goal of this study is to assess the safety of a novel, self- complementary AAV vector in adults with severe hemophilia B.

    Eligibility Criteria

    Inclusion criteria include:

    • 18 years old or older
    • Diagnosis of severe hemophilia B
    • Male
    • Treated/exposed to FIX products (concentrates or fresh, frozen plasma) for at least 10 years or 50 exposure days
    • At least 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes
    • Currently free of inhibitor and no history of inhibitors to FIX protein
    • Negative family history for development of an inhibitor

    Exclusion Criteria include:

    • Active hepatitis B or C infection
    • Exposure to hepatitis B or C and currently on antiviral therapy
    • Inadequately treated HIV infection

    Study Sites

    St. Jude Children’s Research Hospital, Memphis, Tennessee
    Collaborating sites in and outside the U.S.

  2. About this study

    Hemophilia B is a blood disease caused by a missing or abnormal factor IX gene. Genes tell the cells of our bodies how to grow, develop and function. Factor IX is a protein that helps blood clot properly.

    Patients with hemophilia B are almost always male. They do not have enough of the factor IX protein in their blood and experience severe bleeding, often into their joints. This can cause chronic joint disease and lead to disability.

    Factor IX replacement therapy is the only treatment for patients with hemophilia B. Injections are given through the veins in the arm or hand every time a patient has a severe bleed. Treatment may also include frequent factor IX injections on a regular basis to prevent bleeding.

    Researchers have studied gene therapy as a way of permanently fixing the factor IX gene. This study tests the safety of giving a normal factor IX gene to adults with hemophilia B. Researchers will use an inactivated virus to carry the new factor IX gene into the patient’s liver where factor IX is normally made. This virus, also known as a vector, was developed in a laboratory at St. Jude Children’s Research Hospital and has been changed so it cannot cause an infection. It has not been tested in humans.

    Purpose of this clinical trial

    The main purpose of this study is to see if this gene transfer method is safe for adults with hemophilia B.

    Eligibility overview

    • 18 years old or older
    • Diagnosis of severe hemophilia B
    • Male
    • Treated/exposed to FIX products (concentrates or fresh, frozen plasma) for at least 10 years or 50 exposure days
    • At least 3 bleeding episodes per year requiring FIX infusions or prophylactic FIX infusions because of frequent prior bleeding episodes
    • Currently free of inhibitor and no history of inhibitors to FIX protein
    • Negative family history for development of an inhibitor
  3. AGT4HB Quick View
    Sponsors St. Jude Children’s Research Hospital    
    ClinicalTrials.gov identifier NCT00979238
    Trial Start Date August 2009
    Estimated Enrollment 16
    Study Type Interventional
    Study Phase Phase I
    Conditions Hemophilia B
    Ages 18 and older
    Principal investigator Ulrike Reiss, MD
    Study Sites St. Jude Children’s Research Hospital and collaborating sites in and outside the U.S.
    For a consultation or to discuss AGT4HB
    St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.