Safety and Efficacy of T Cell Genetic Immunotherapy for HIV

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
VIRxSYS Corporation
ClinicalTrials.gov Identifier:
NCT00131560
First received: August 16, 2005
Last updated: June 7, 2011
Last verified: June 2011
  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 2

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:


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
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: 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:
Publications:

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 July 26, 2014