Safety and Efficacy of T Cell Genetic Immunotherapy for HIV

NCT00131560 | Unknown Phase 2 DMC

• 1 other identifier: VRX496-USA-05-002
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

HIV Infection

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Change in viral load

  1 Year

• Change in CD4 counts

  1 Year

• Safety

  15 Years

Secondary Outcomes (3)

• Immune function

  1 Year

• AIDS related illness

  1 Year

• Persistence of vector modified cells

  15 Years

Study Arms (1)

A

OTHER

Genetic: VRX496-Modified Autologous T cells

Interventions

VRX496-Modified Autologous T cells GENETIC

Genetic: Anti-HIV antisense

A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• VIRxSYS Corporation: lead

Study Sites (5)

Stanford AIDS Clinical Trials Unit

Palo Alto, California, 94304, United States

Location

CIRCLE Medical, LLC

Norwalk, Connecticut, 06851, United States

Location

Steinhart Medical Associates

Miami, Florida, 33133, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Jacobi Medical Center

The Bronx, New York, 10461, United States

Location

Related Publications (5)

• 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. doi: 10.1089/hum.2005.16.17.

  PMID: 15703485 BACKGROUND

• 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. doi: 10.1002/jgm.726.

  PMID: 15693055 BACKGROUND

• 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. doi: 10.1002/jgm.593.

  PMID: 15352069 BACKGROUND

• 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. doi: 10.1128/JVI.78.13.7079-7088.2004.

  PMID: 15194784 BACKGROUND

• 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. doi: 10.1016/j.ymthe.2004.03.005.

  PMID: 15194057 BACKGROUND

Related Links

• VIRxSYS Corporation website

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Tessio Rebello, PhD

  VIRxSYS Corporation

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: August 16, 2005
• First Posted: August 18, 2005
• Study Start: July 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: June 1, 2023
• Last Updated: June 8, 2011

Record last verified: 2011-06

Locations

US (5)