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

• ClinicalTrials.gov Identifier: NCT01252641
• Recruitment Status: Completed
• First Posted: December 3, 2010
• Last Update Posted: September 20, 2019
• Sponsor: Sangamo Therapeutics
• Information provided by (Responsible Party): Sangamo Therapeutics

Tracking Information

• First Submitted Date: November 29, 2010
• First Posted Date: December 3, 2010
• Last Update Posted Date: September 20, 2019
• Study Start Date: November 2010
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 24, 2011)

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

Original Primary Outcome Measures (submitted: December 1, 2010)

Treatment related adverse events [ Time Frame: 12 months ]

Number of participants who report adverse events as a measure of safety and tolerability

Current Secondary Outcome Measures (submitted: December 1, 2010)

• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• HIV
• HIV Infection

Intervention

Biological: SB-728-T

Each infusion will be 5-30 billion modified CD4+ T-cells

Study Arms

Experimental: SB-728-T

Subjects will receive one intravenous infusion of SB-728-T

Intervention: Biological: SB-728-T

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 20, 2014): 21
• Original Estimated Enrollment (submitted: December 1, 2010): 14
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01252641
• Other Study ID Numbers: SB-728-1002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Sangamo Therapeutics
• Original Responsible Party: Sangamo BioSciences, Inc., Sangamo BioSciences, inc.
• Current Study Sponsor: Sangamo Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Sangamo Therapeutics
• Verification Date: September 2019