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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 3 Subjects will receive a single infusion of 0.5-1.0 x 1010 SB-728-T |
|
| Cohort 2 | Experimental | 3 Subjects will receive a single infusion of 2.0 x 1010 SB-728-T |
|
| Cohort 3 | Experimental | 3 Subjects will receive a single infusion of 3.0 x 1010 SB-728-T |
|
| Cohort 4 | Experimental | Up to 4 HAART failure subjects will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T |
|
| Cohort 5 | Experimental | Up to 20 subjects with heterozygote CCR5 delta-32 mutation will receive a single intravenous infusion of 0.5 to 3.0 x 1010 SB-728-T. Cohort 5 subjects will undergo a structured treatment interruption 2 months following infusion in which their anti-retroviral therapy will be discontinued for 16 weeks. HAART will be reinstituted in subjects whose CD4+ cell counts drop to <350 cells/mm3 and/or whose HIV-RNA increases to >100,000 on three consecutive weekly measurements. At the end of the STI, subjects with a sustained detectable viral load will be reinstituted on HAART. Subjects with HIV RNA levels below the limit of detection will remain off HAART. Subjects with an undetectable viral load will remain off HAART until HIV RNA levels are detectable or their CD4 count drops below 350 cell/mm3 on three consecutive weekly measurements. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SB-728-T | Genetic | Each infusion will be 5-30 billion ZFN modified CD4+ T-cells |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety - Treatment related adverse events | 12 months after the first infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Evaluate the long-term persistence and activity of CCR5 ZFN-modified autologous T-Cells | 12 months after the first infusion |
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Inclusion Criteria:
Cohort 1, 2 and 3 (Enrollment Completed)
Cohort 5:
Cohort 4
Exclusion Criteria:
Cohort 4 only:
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| Name | Affiliation | Role |
|---|---|---|
| Winson Tang, M.D. | Sangamo Therapeutics | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UCLA Center for AIDS Research and Education | Los Angeles | California | 90035 | United States | ||
| Orange Coast Medical Group |
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|
| Newport Beach |
| California |
| 92663 |
| United States |
| Quest Clinical Research | San Francisco | California | 94115 | United States |
| Circle CARE Center, LLC | Norwalk | Connecticut | 06851 | United States |
| Orlando Immunology Center | Orlando | Florida | 32803 | United States |
| Central West Clinical Research, Inc. | St Louis | Missouri | 63108 | United States |
| Southwest CARE Center | Santa Fe | New Mexico | 87505 | United States |
| Ricky K Hsu, MD, PC | New York | New York | 10011 | United States |
| Gordon Crofoot, MD, PA | Houston | Texas | 77098 | United States |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
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