Study of Autologous T-cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases in HIV-Infected Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sangamo Biosciences
ClinicalTrials.gov Identifier:
NCT01252641
First received: November 29, 2010
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

This research study is being carried out to study a new way to possibly treat human immunodeficiency virus (HIV). The agent is called SB-728-T which are CD4+ T-cells obtained from an individual that are genetically modified at the CCR5 gene by Zinc Finger Nucleases. The CCR5 gene is required for certain types of HIV to enter into and infect 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 the CCR5 gene on their T-Cells. These people remain healthy and are resistant to infection with HIV. Other people have a low number of CCR5 genes on their T-cells and their HIV disease is less severe and is slower to cause disease (AIDS).

The purpose of this research study is to find out whether SB-728-T is safe to give to humans and find out how this affects HIV.


Condition Intervention Phase
HIV
HIV Infection
Biological: SB-728-T
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open Label, Single Infusion Study of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases (SB-728-T) in HIV Infected Subjects

Resource links provided by NLM:


Further study details as provided by Sangamo Biosciences:

Primary Outcome Measures:
  • Evaluate the safety and tolerability of SB-728-T cells infusion in HIV-1 positive subjects [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Evaluate the safety and tolerability of a single infusion of 5-30 billion SB-728-T cells in HIV-1 positive subjects


Secondary Outcome Measures:
  • Evaluate persistence of HIV as measured by HIV-1 RNA, [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Change in CD4+ T-cell count [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • Persistence of SB-728-T in the peripheral blood [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: November 2010
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SB-728-T
Subjects will receive one intravenous infusion of SB-728-T
Biological: SB-728-T
Each infusion will be 5-30 billion modified CD4+ T-cells

Detailed Description:

Laboratory studies have shown that when CD4+ T-cells are modified with Zinc Finger Nucleases SB-728, HIV is prevented from killing the CD4+ T-cells. On the basis of these laboratory results, there is the potential that this may work in humans infected with HIV and improve their immune system by allowing their CD4+ T-cells to survive longer.

The new treatment to be studied will involve removing white blood cells from the blood that contain CD4+ T-cells. The extracted CD4+ T-cells are then genetically modified by the Zinc finger Nucleases to be resistant to infection 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 the individual. 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented HIV infection
  • CD4+ T-cell count >500 cell per millimeter cubed (cells/mm3)
  • CD4+ T-cell nadir of >400 cells/mm3
  • HIV viral load >1,000 copies per milliliter (mL)

Exclusion Criteria:

  • Any viral hepatitis
  • Acute HIV infection
  • HIV viral load >1,000,000 copies/mL
  • Active or recent (prior 6 months) AIDS defining complication
  • Any HIV medications within the past 12 weeks
  • Cancer or malignancy that has not been in remission for at least 5 years with the exception of successfully treated basal cell carcinoma of the skin
  • Current diagnosis of NYHA grade 3 or 4 congestive heart failure or uncontrolled angina or arrhythmias
  • History of bleeding problems
  • Use of chronic steroids in past 30 days
  • Pregnant or breast feeding
  • Active drug or alcohol abuse
  • Serious illness in past 30 days
  • Currently participating in another clinical trail or any prior gene therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01252641

Locations
United States, California
UCLA CARE Center
Los Angeles, California, United States, 90035
Orange Coast Medical Group
Newport Beach, California, United States, 92663
Quest Clinical Research
San Francisco, California, United States, 94115
United States, Florida
Orlando Immunology Center
Orlando, Florida, United States, 32803
Sponsors and Collaborators
Sangamo Biosciences
Investigators
Study Director: Winson Tang, M.D. Sangamo BioSciences, Inc.
  More Information

No publications provided

Responsible Party: Sangamo Biosciences
ClinicalTrials.gov Identifier: NCT01252641     History of Changes
Other Study ID Numbers: SB-728-1002
Study First Received: November 29, 2010
Last Updated: February 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Sangamo Biosciences:
HIV

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on September 14, 2014