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

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 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:

MedlinePlus related topics: Genes and Gene Therapy HIV/AIDS

U.S. FDA Resources

Further study details as provided by Sangamo Therapeutics:

Primary Outcome Measures:

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


Enrollment:	21
Study Start Date:	November 2010
Study Completion Date:	May 2015
Primary Completion Date:	December 2014 (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 (Adult, Senior)
Sexes Eligible for Study:	All
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 Therapeutics

Investigators


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

More Information


Responsible Party:	Sangamo Therapeutics
ClinicalTrials.gov Identifier:	NCT01252641 History of Changes
Other Study ID Numbers:	SB-728-1002
Study First Received:	November 29, 2010
Last Updated:	May 18, 2015

Keywords provided by Sangamo Therapeutics:


HIV

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases	Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases

ClinicalTrials.gov processed this record on July 17, 2017