Ignite Creation Date:
2025-12-25 @ 2:39 AM
Ignite Modification Date:
2025-12-26 @ 6:20 PM
Study NCT ID:
NCT00842634
Status:
COMPLETED
Last Update Posted:
2019-02-08
First Post:
2009-02-04
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 for HIV
Sponsor:
University of Pennsylvania
Organization:
Study Overview
Official Title:
A Phase I Study of Autologous T-Cells Genetically Modified at the CCR5 Gene by Zinc Finger Nucleases SB-728 in HIV-Infected Patients
Status:
COMPLETED
Status Verified Date:
2019-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Zinc-Finger
Brief Summary:
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 common types of HIV (CCR5 tropic) 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 T-cells are those 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).
In order to delete the CCR5 protein on the T cells, this study will isolate large numbers of T-cells from subjects, and then deliver the ZFNs using a delivery vehicle called a viral vector. The viral vector used in this study is called an adenoviral vector. The vector is added to the cells at the beginning of the manufacture process and the ZFNs knock out the CCR5 protein. By the time T-cells are returned to subjects, there is minimal adenovirus or ZFN present. The removal of the CCR5 protein on the T-cells subjects receive, however, is permanent.
The purpose of this research study is to find out whether "zinc finger" modified T-cells are
1. safe to give to humans and
2. find how "zinc finger" modified T cell affects HIV
This is an experimental study. Laboratory studies have shown that when CD4 T-cells are modified with "zinc fingers", HIV is prevented from killing the CD4 T cells. On the basis of these laboratory results, there is the potential that "zinc fingers" may work in humans infected with HIV and improve their immune system by allowing their CD4 T-cells to survive longer (HIV usually kills T cells it infects).
All subjects who receive ZFN Modified CD4+T cells will enroll in a Long Term, Follow-up study to monitor subjects. Subjects will be followed every 3 months for four years. If the ZFN Modified CD4+T cells are no longer found in the blood after four years, then subjects will be contacted yearly for the next 6 years. If the ZFN Modified CD4+T cells are found in the blood at year four, then the subjects will continue to be seen once a year until the ZFN Modified CD4+T cells are no longer found in the blood for a maximum of 10 years.
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).
In order to delete the CCR5 protein on the T cells, this study will isolate large numbers of T-cells from subjects, and then deliver the ZFNs using a delivery vehicle called a viral vector. The viral vector used in this study is called an adenoviral vector. The vector is added to the cells at the beginning of the manufacture process and the ZFNs knock out the CCR5 protein. By the time T-cells are returned to subjects, there is minimal adenovirus or ZFN present. The removal of the CCR5 protein on the T-cells subjects receive, however, is permanent.
The purpose of this research study is to find out whether "zinc finger" modified T-cells are
1. safe to give to humans and
2. find how "zinc finger" modified T cell affects HIV
This is an experimental study. Laboratory studies have shown that when CD4 T-cells are modified with "zinc fingers", HIV is prevented from killing the CD4 T cells. On the basis of these laboratory results, there is the potential that "zinc fingers" may work in humans infected with HIV and improve their immune system by allowing their CD4 T-cells to survive longer (HIV usually kills T cells it infects).
All subjects who receive ZFN Modified CD4+T cells will enroll in a Long Term, Follow-up study to monitor subjects. Subjects will be followed every 3 months for four years. If the ZFN Modified CD4+T cells are no longer found in the blood after four years, then subjects will be contacted yearly for the next 6 years. If the ZFN Modified CD4+T cells are found in the blood at year four, then the subjects will continue to be seen once a year until the ZFN Modified CD4+T cells are no longer found in the blood for a maximum of 10 years.
Detailed Description:
Cohort 1 - Patients who have failed two more HAART regimens (6 subjects)
Cohort 2 - Patients doing well on a stable antiretroviral medication (6 subjects)
Cohort 3 - Patients who have an undetectable viral load on HAART who have exhibited suboptimal CD4+ T cell gains during long term antiretroviral therapy. This group will not participate in the structured treatment interruption. (6 subjects)
1. Eligibility: Physical Exam, Medical History, Blood Draws for clinical labs and research.
2. 1st Procedure to collect T cells (called apheresis)
3. 2nd Procedure to collect T cells (called apheresis occurs \~3 weeks after 1st Apheresis)and Rectal Biopsy
4. Clinic visit: Physical Exam, Blood Draw for clinical labs and research (\~1 to 2 weeks after 2nd Apheresis)
5. Infusion of ZFN modified T cells (\~2weeks after Clinic Visit)
Cohort 1 and Cohort 3 only:
6. Follow up Clinic Visits 48, 72 hours; 1,2,3,6 weeks; 2,3,6, 9 months after ZFN infusion.
Cohort 2 Only:
6\. Stop Antiretroviral Medications 4 Weeks after ZFN modified T cell Infusion.
7\. Follow-up Clinic Visits 6, 8, 10, 12, 16, weeks after ZFN modified T cell Infusion.
8\. Restart Antiretroviral Medications 20 weeks after ZFN modified T cell Infusion.
9\. Follow-up Clinic Visits: monthly visits until no detectable HIV found in blood.
Cohort 2 - Patients doing well on a stable antiretroviral medication (6 subjects)
Cohort 3 - Patients who have an undetectable viral load on HAART who have exhibited suboptimal CD4+ T cell gains during long term antiretroviral therapy. This group will not participate in the structured treatment interruption. (6 subjects)
1. Eligibility: Physical Exam, Medical History, Blood Draws for clinical labs and research.
2. 1st Procedure to collect T cells (called apheresis)
3. 2nd Procedure to collect T cells (called apheresis occurs \~3 weeks after 1st Apheresis)and Rectal Biopsy
4. Clinic visit: Physical Exam, Blood Draw for clinical labs and research (\~1 to 2 weeks after 2nd Apheresis)
5. Infusion of ZFN modified T cells (\~2weeks after Clinic Visit)
Cohort 1 and Cohort 3 only:
6. Follow up Clinic Visits 48, 72 hours; 1,2,3,6 weeks; 2,3,6, 9 months after ZFN infusion.
Cohort 2 Only:
6\. Stop Antiretroviral Medications 4 Weeks after ZFN modified T cell Infusion.
7\. Follow-up Clinic Visits 6, 8, 10, 12, 16, weeks after ZFN modified T cell Infusion.
8\. Restart Antiretroviral Medications 20 weeks after ZFN modified T cell Infusion.
9\. Follow-up Clinic Visits: monthly visits until no detectable HIV found in blood.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: