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

HIV Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01252641
• Other study ID #: SB-728-1002
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: November 2010
• Est. completion date: May 2015

Study information

• Verified date: September 2019
• Source: Sangamo Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: May 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• HIV
• HIV Infection
• HIV Infections

Intervention

Biological:
• SB-728-T
Each infusion will be 5-30 billion modified CD4+ T-cells

Locations

Country	Name	City	State
United States	UCLA CARE Center	Los Angeles	California
United States	Orange Coast Medical Group	Newport Beach	California
United States	Orlando Immunology Center	Orlando	Florida
United States	Quest Clinical Research	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Sangamo Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety and tolerability of SB-728-T cells infusion in HIV-1 positive subjects	Evaluate the safety and tolerability of a single infusion of 5-30 billion SB-728-T cells in HIV-1 positive subjects	12 months
Secondary	Evaluate persistence of HIV as measured by HIV-1 RNA,		12 months
Secondary	Change in CD4+ T-cell count		12 months
Secondary	Persistence of SB-728-T in the peripheral blood		12 months