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

Sponsor

Sangamo Therapeutics (Industry)

Overall Status

Completed

CT.gov ID

NCT01252641

Collaborator

(none)

Enrollment

Locations

Arm

53.9

Duration (Months)

5.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HIV HIV Infection	Biological: SB-728-T	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Dec 1, 2014

Actual Study Completion Date :

May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Evaluate the safety and tolerability of SB-728-T cells infusion in HIV-1 positive subjects [12 months]
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, [12 months]
Change in CD4+ T-cell count [12 months]
Persistence of SB-728-T in the peripheral blood [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	UCLA CARE Center	Los Angeles	California	United States	90035
2	Orange Coast Medical Group	Newport Beach	California	United States	92663
3	Quest Clinical Research	San Francisco	California	United States	94115
4	Orlando Immunology Center	Orlando	Florida	United States	32803

Sponsors and Collaborators

Sangamo Therapeutics

Investigators

Study Director: Winson Tang, M.D., Sangamo BioSciences, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Sangamo Therapeutics

ClinicalTrials.gov Identifier:

NCT01252641

Other Study ID Numbers:

SB-728-1002

First Posted:

Dec 3, 2010

Last Update Posted:

Sep 20, 2019

Last Verified:

Sep 1, 2019

Keywords provided by Sangamo Therapeutics

HIV

Additional relevant MeSH terms:

HIV Infections

Study Results

No Results Posted as of Sep 20, 2019