Safety and Efficacy of T Cell Genetic Immunotherapy for HIV - Full Text View

Sponsor:	VIRxSYS Corporation
Information provided by:	VIRxSYS Corporation
ClinicalTrials.gov Identifier:	NCT00131560

Purpose

This study uses autologous (one's own) CD4 T cells modified with a viral vector expressing a genetic antisense targeting HIV, this vector is called VRX496. Study treatment is by intravenous infusion of vector modified cells and infusions will be provided every other week for a total of 4 or 8 doses. These modified cells, once infused, may provide immune support and are not destroyed by HIV, and thus may delay or reverse HIV disease progression. The study will enroll up to 40 male and female HIV-positive subjects in up to 8 centers. Subjects will be 18 years of age and over who have failed or are intolerant to at least one triple combination of antiretroviral drugs. Subjects must have a viral load between 5,000 and 200,000 copies/ml and a CD4+ count of ≥150, be in good health and have no evidence of active opportunistic infection, heart disease, or bleeding disorders. Subjects must not be on corticosteroids, immunomodulating agents or hydroxyurea. Subjects must not have received an AIDS vaccine or any investigational gene therapy product at any time. Females must not be pregnant or breastfeeding.

Condition	Intervention	Phase
HIV Infection	Genetic: VRX496-Modified Autologous T cells	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II, Open-label, Multicenter Study to Evaluate the Safety, Tolerability, and Biological Activity of Single and Repeated Doses of Autologous T Cells Transduced With VRX496 in HIV-Positive Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by VIRxSYS Corporation:

Primary Outcome Measures:

Change in viral load [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
Change in CD4 counts [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
Safety [ Time Frame: 15 Years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Immune function [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
AIDS related illness [ Time Frame: 1 Year ] [ Designated as safety issue: Yes ]
Persistence of vector modified cells [ Time Frame: 15 Years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	60
Study Start Date:	July 2005
Estimated Study Completion Date:	June 2023
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A	Genetic: VRX496-Modified Autologous T cells Genetic: Anti-HIV antisense

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Sero-positive for infection with HIV and failed, or be intolerant to, at least one triple combination of antiretroviral agent
If on antiretroviral therapy, subject must be willing to continue on current antiretroviral therapy; or if discontinues antiretroviral therapy must have a wash-out period of 6 weeks prior to screening; or if not on antiretroviral therapy must be willing to remain off antiretroviral therapy for the duration of the study (i.e. up to 1 year)
Male or female, 18 years of age and older
Karnofsky Performance score of 80 or higher
Stable HIV viral load between 5,000 and 200,000 copies/mL at the time of screening. Stable will be defined as a variation of less than 0.5 log10 in the 3 months prior to screening while on a stable regimen or no therapy
CD4 T cell count equal to or greater than 150 cells per μL at the time of screening
A body weight greater than 50 Kg
Adequate venous access and no other contraindications for leukapheresis
Subject must be willing to comply with study-mandated evaluations

Exclusion Criteria:

A history of any type of cancer or malignancy, with the exception of (successfully) treated basal cell or squamous cell carcinoma of the skin
A history or any features on physical examination indicative of cardiac disease or hemodynamic instability
Any history or any features on physical examination indicative of a bleeding diathesis
Previous treatment with any HIV experimental vaccine or any gene therapy products
A positive signal for VSV-G antibodies and/or VSV-G DNA in the blood at screening
Any of the following lab results:
- Hemoglobin: <10 (males); <9.5 (females) g/dL
- Absolute neutrophil count: < 1000/μL
- Platelet count: <100,000/mm3
- Serum creatinine: > 1.5 mg/dL (133µ mol/L)
- AST or ALT: > 2.5 times the upper limit of normal
- Total serum bilirubin: > 1.5 times the upper limit of normal
- Proteinuria: 2+ on urine dipstick
Subjects must not be breastfeeding, be pregnant, or unwilling to use acceptable methods of birth control
Subjects must not be on chronic oral corticosteroids within 30 days of screening - (if subjects are prescribed a brief course of oral corticosteroids the use should be limited to less than 1 week), hydroxyurea, or immunomodulating agents (e.g., IL 2, interferon-gamma, granulocyte colony stimulating factors, etc.) within 30-days of screening or foreseeably need any of these within the study period
Subjects must not be using aspirin, dipyridamole, warfarin or any other medication likely to affect platelet function or other aspects of blood coagulation during the period when leukapheresis is scheduled
Subjects must not suffer from active drug or alcohol dependence or abuse, to an extent that, in the opinion of the investigator, would interfere with their ability to comply with study requirements
Any serious illnesses or acute opportunistic infection
Any other illness or condition which in the opinion of the investigator would exclude the subject from the study
Subjects unable or unwilling to give written informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00131560

Locations

United States, California
Stanford AIDS Clinical Trials Unit
Palo Alto, California, United States, 94304
United States, Connecticut
CIRCLE Medical, LLC
Norwalk, Connecticut, United States, 06851
United States, Florida
Steinhart Medical Associates
Miami, Florida, United States, 33133
United States, Kentucky
University of Kentucky
Lexington, Kentucky, United States, 40536
United States, New York
Jacobi Medical Center
Bronx, New York, United States, 10461

Sponsors and Collaborators

VIRxSYS Corporation

Investigators

Study Director:

Tessio Rebello, PhD

VIRxSYS Corporation

More Information

Additional Information:

VIRxSYS Corporation website This link exits the ClinicalTrials.gov site

Publications:

Manilla P, Rebello T, Afable C, Lu X, Slepushkin V, Humeau LM, Schonely K, Ni Y, Binder GK, Levine BL, MacGregor RR, June CH, Dropulic B. Regulatory considerations for novel gene therapy products: a review of the process leading to the first clinical lentiviral vector. Hum Gene Ther. 2005 Jan;16(1):17-25. Review. Erratum in: Hum Gene Ther. 2005 Feb;16(2):279.

Ni Y, Sun S, Oparaocha I, Humeau L, Davis B, Cohen R, Binder G, Chang YN, Slepushkin V, Dropulic B. Generation of a packaging cell line for prolonged large-scale production of high-titer HIV-1-based lentiviral vector. J Gene Med. 2005 Jun;7(6):818-34.

Lu X, Humeau L, Slepushkin V, Binder G, Yu Q, Slepushkina T, Chen Z, Merling R, Davis B, Chang YN, Dropulic B. Safe two-plasmid production for the first clinical lentivirus vector that achieves >99% transduction in primary cells using a one-step protocol. J Gene Med. 2004 Sep;6(9):963-73.

Lu X, Yu Q, Binder GK, Chen Z, Slepushkina T, Rossi J, Dropulic B. Antisense-mediated inhibition of human immunodeficiency virus (HIV) replication by use of an HIV type 1-based vector results in severely attenuated mutants incapable of developing resistance. J Virol. 2004 Jul;78(13):7079-88.

Humeau LM, Binder GK, Lu X, Slepushkin V, Merling R, Echeagaray P, Pereira M, Slepushkina T, Barnett S, Dropulic LK, Carroll R, Levine BL, June CH, Dropulic B. Efficient lentiviral vector-mediated control of HIV-1 replication in CD4 lymphocytes from diverse HIV+ infected patients grouped according to CD4 count and viral load. Mol Ther. 2004 Jun;9(6):902-13.

Responsible Party:	Tessio Rebello/ Vice President Clinical Affairs, VIRxSYS Corporation
ClinicalTrials.gov Identifier:	NCT00131560 History of Changes
Other Study ID Numbers:	VRX496-USA-05-002
Study First Received:	August 16, 2005
Last Updated:	June 7, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by VIRxSYS Corporation:

HIV, gene therapy, leukapheresis, autologous CD4 T cell, lentivector

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases

Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on February 13, 2012