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Phase 1 Dose Escalation Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Patients

Sponsored by Sangamo Biosciences

Phase Quota
Phase 1

This research study is being carried out to study a new way to possibly treat HIV. This agent is called a "Zinc Finger Nuclease" or ZFN for short. ZFNs are proteins that can delete another protein named CCR5. This CCR5 protein is required for certain types of HIV (CCR5 tropic) to enter into and infect your T-cells. T cells are one of the white blood cells used by the body to fight HIV. The most important of these are called "CD4 T-cells." Some People are born without CCR5 on their T-cells. These people remain healthy and are resistant to infection with HIV. Other people have a low number of CCR5 on their T-cells, and their HIV disease is less severe and is slower to cause disease (AIDS). Even with no detectable levels of HIV in the blood, HIV remains in some tissues in the body, primarily the gut tissue. HIV infects the CD4+ T-cells including in the blood and gut. The new treatment to be studied will involve removing white blood cell from the blood that contains CD4+ T-cells. The extracted CD4+ T-cells are then genetically modified by the ZFNs to be resistant to infection by HIV by removing the CCR5 gene from the surface of the CD4+ T cell where HIV enters the cell. Additional genetically modified cells are manufactured and then re-infused back into you. Researchers hope that these genetically modified cells will be resistant to infection by HIV and will be able to reproduce additional resistant CD4+ T-cells in your body. Laboratory studies have shown that when CD4+ T-cells are modified with ZFNs, HIV is prevented from killing the CD4+ T-cells. On the basis of these laboratory results, thre is the potential that ZFNs may work in humans infected with HIV and improve their immune system by allowing their CD4+ T-cells to survive longer. The purpose of this research study is to find out whether "zinc finger" modified CD4+ T-cells are safe to give to humans and find how "zinc finger" modified T-cell affects HIV.

Study Start Date: December 2009

Estimated Completion Date: December 2014

Specialties: Internal Medicine: Infectious Disease Nursing: Immuno/Infectious Dz Infectious Disease: Basic Science/Genetics,HIV/Immunodeficiency Physician Assistant: Infectious Disease

Interventions

  • Genetic: SB-728-T

Inclusion criteria

  • Documented HIV infection prior to study entry
  • Cohort 1, 2 and 3:
    • At least 2 years of continuous antiretroviral therapy
    • Undetectable viral load since 6 months of beginning therapy
    • CD4+ T-cell count > 200 cells/mm3 and </= 500 cells/mm3 at screen
  • Cohort 4
  • CD4+ T cell count >/= 250 cells/mm3
  • HIV-1 RNA </=1,000 copies/mL
  • On stable antiretroviral medication (no changes within 4 weeks of screening) and willing to continue on current therapy through week 8 after infusion

Exclusion criteria

  • Acute or chronic hepatitis B or hepatitis C infection
  • Active or recent (in prior 6 months) AIDS defining complication
  • Any cancer or malignancy within the past 5 years, with the exception of successfully treated basal cell or squamous cell carcinoma of the skin or low grade (0 or 1) anal or cervical dysplasia
  • Current diagnosis of NYHA grade 3 or 4 CHF, uncontrolled angina or uncontrolled arrhythmias
  • History or any features on physical examination indicative of a bleeding diathesis
  • Previous treatment with any HIV experimental vaccine within 6 months prior to screening, or any previous gene therapy using an integrating vector
  • Use of chronic corticosteroids, hydroxyurea, or immunomodulating agents (e.g., interleukin-2, interferon-alpha or gamma, granulocyte colony stimulating factors, etc.) within 30 days prior to enrollment
  • Breast-feeding, pregnant or unwilling to use acceptable methods of birth control for 6 months following the last infusion of SB-728-T cells
  • warfarin or any other medication that is likely to affect platelet function or other aspects of blood coagulation during the 2 week period prior to leukapheresis
  • Active drug or alcohol use or dependence
  • Serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
  • Recent vaccination or intercurrent illness (within 5 weeks prior to infusion)
  • Have an allergy or hypersensitivity to study product excipients (human serum albumin, DMSO and Dextran 40)
  • Subjects who are currently taking maraviroc or have received maraviroc within 6 months prior to screening
  • Cohort 4 only:
    • HIV-1 RNA >1,000 copies/mL at screen and not responding to current antiviral therapy
    • CD4+ T cell count >350 cells/mm3

Study Locations And Contact Information

  • Orange Coast Medical Group, Newport Beach California
  • Gordon Crofoot MD PA, Houston Texas
  • Ricky K Hsu MD PC, New York New York
  • UCLA Center for AIDS Research and Education, Los Angeles California
  • Circle CARE Center LLC, Norwalk Connecticut
  • Southwest CARE Center, Santa Fe New Mexico
  • Quest Clinical Research, San Francisco California
  • Central West Clinical Research Inc, St Louis Missouri
  • Orlando Immunology Center, Orlando Florida

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