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HIVPhase 1NCT00295477

Evaluate the Tolerability and Therapeutic Effects of Repeated Doses of Autologous T Cells With VRX496 in HIV

A Phase 1 study testing VRX496 in people with HIV, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The study is intended for individuals who are doing well on HAART therapy. In Step 1 of the trial, individuals will be given up to 6 infusions of the study drug VRX496 to see the effect on viral load and CD4 counts. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV
What is being tested?
VRX496
Type of treatment
Injection or infusion
How many people
25 participants
Where
1 siteUnited States
Study dates
Jan 2006to Dec 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HIV-1 positive by western blot or detection of HIV RNA in blood and responding to combination antiviral therapy
  • No changes in antiretroviral medications within past 4 weeks of study entry and willing to continue on current therapy for the duration of the study
  • 18 years of age and older
  • Karnofsky Performance score of greater than 80
  • HIV viral load < 59 copies/mL
  • CD4 T cell count > 350 cells per uL
  • adequate venous access

Who cannot join

  • HIV seroconversion within past year
  • History of cancer (other than a removed basal or squamous cell of the skin)
  • History of congestive heart failure.
  • Previous treatment with HIV experimental vaccine within past year
  • Previous treatment with any gene therapy
  • Positive serology for Vesicular Stomatitis Virus (VSV-G or VSV-G DNA)
Show all 14Show fewer
  • Currently breastfeeding, pregnant, or unwilling to use birth control
  • Using oral corticosteroids, hydroxyurea, or immunomodulating agents (IL-2, interferon-gamma, granulocyte colony stimulating factors, megestrol acetate) within the past 30 days or foresee the need to use these during the study period.
  • Are presently drug or alcohol dependent
  • Have other serious illness or acute opportunistic infection or bacterial infection requiring systemic treatment and/or hospitalization within the past 30 days
  • Have chronic hepatitis B or hepatitis C
  • Have an active AIDS defining illness
  • Have an allergy or hypersensitivity to human serum albumin, DMSO or Dextran 40
  • Have diabetes or a coagulopathy with in the opinion of the investigator would exclude subjects from participating in rectal biopsy.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pennsylania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Phase I/II, Open-label, Single Center Study to Evaluate the Tolerability, Trafficking and Therapeutic Effects of Repeated Doses of Autologous T Cells Transduced With VRX496 in HIV Infected Subjects

The study is intended for individuals who are doing well on HAART therapy. In Step 1 of the trial, individuals will be given up to 6 infusions of the study drug VRX496 to see the effect on viral load and CD4 counts. If individuals have no serious adverse effects from the infusions of VRX496 and the viral load and CD4 counts remain stable, they may go on to Step 2 of the study. In Step 2, individuals will stop taking their HAART medication and their viral load, CD4 counts and the number of VRX496 in T cells will be monitored.

All subjects who receive VRX496 T cells will enroll in a Long-Term Follow-up study to monitor subjects. Subjects will be followed every 6 months for five years following the 1st infusion of the T cells. If the VRX496 T cells are no longer found in the blood after five years, then subjects will be contacted yearly for the next 10 years. If the VRX496 T cells are found in the blood at five years after the 1st infusion of T cells, then the subjects will continue to be seen once a year until the VRX496 T cells are no longer found in the blood for a maximum of 15 years.

Read the detailed description

HIV-based antisense vectors may provide several important advantages over current HIV combination therapies. VIRxSYS Corporation (VIRxSYS) is developing the candidate clinical vector VRX496. VRX496 is an HIV-based lentiviral vector containing an anti-HIV antisense sequence targeted to the HIV envelope (env) coding sequence. First, HIV-1 vectors are likely to be less toxic than current combination drug therapies because the genetic antisense antiviral is expressed only in cells that become infected with wt-HIV. The payload is located upstream of a major splice acceptor site and is thus dependent on the expression of Tat and Rev proteins that are provided by wt-HIV. Second, the length of the antisense region is over 900 nucleotides long, making it difficult for wt-HIV to create resistant strains that are sufficiently fit to cause disease. Third, HIV vectors are predicted to be safe because no novel genetic sequences are introduced into the patient (i.e., no novel functional genes are contained in the HIV-1 vector). All the sequences present in the vector are derived from highly conserved regions of wt-HIV that would almost certainly be present in any HIV-1-infected individual. The HIV sequences that are used to create VRX496 are solely derived from pNL4-3, a prototypic HIV-1 molecular clone that is derived from two North American strains of HIV-1.

In the present trial, T cells will be harvested from infected individuals, transduced ex vivo with the vector at the University of Pennsylvania, and then reintroduced by autologous transfusions. VIRxSYS recently completed a Phase 1 clinical study at the University of Pennsylvania of the vector VRX496 in 5 HIV-positive subjects who had failed at least two HAART regimens. Data available to date for the primary endpoints, viral load and CD4 counts, are promising. Specifically, 4 of 5 subjects had stable or increased CD4 counts, and viral loads were stable in 4 of 5 patients, and decreased by 1.7 log in 1 of 5 subjects following a single infusion of VRX496 T cells. In the present trial, subjects will receive up to 6 infusions of VRX496 modified CD4 T cells, and then undergo a series of tests, including rectal mucosal biopsies, to determine the longevity and trafficking of the VRX496 T cells. In addition, subjects will have the opportunity to have a supervised drug holiday (structured treatment interruption) to determine if the VRX496 have an antiviral effect.

Conditions
HIV
Being tested
VRX496
Keywords
HIV, Treatment Experienced

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VRX496Genetic

    In Step 1 of the protocol, each subject will receive up to 2 cycles of VRX496. Each treatment cycle consists of 3 infusions of VRX496.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of serious adverse events & dose related toxicity.

    Measured: 18 months

  2. Effects on viral load and CD4 counts from baseline through STI.

    Measured: 18 months

  3. Estimate antiviral effects of VRX496 after STI.

    Measured: 18 months

Secondary outcomes (1)

  1. Determine persistence and number of VRX496 containing T cells

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2006 (estimated)
  2. Study startJan 2006
  3. Primary completionApr 2010
  4. Study completionDec 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00295477
Sponsor's protocol ID
Tebas 066290 - Protocol 802456
Other IDs
NIAID U19-A1066290
Status last verified
Oct 2019
First submitted
21 Feb 2006
Last updated
23 Oct 2019
Results posted
No
Data monitoring committee
Yes
FDA-regulated device
No

Publications

  • Tebas P, Stein D, Binder-Scholl G, Mukherjee R, Brady T, Rebello T, Humeau L, Kalos M, Papasavvas E, Montaner LJ, Schullery D, Shaheen F, Brennan AL, Zheng Z, Cotte J, Slepushkin V, Veloso E, Mackley A, Hwang WT, Aberra F, Zhan J, Boyer J, Collman RG, Bushman FD, Levine BL, June CH. Antiviral effects of autologous CD4 T cells genetically modified with a conditionally replicating lentiviral vector expressing long antisense to HIV. Blood. 2013 Feb 28;121(9):1524-33. doi: 10.1182/blood-2012-07-447250. Epub 2012 Dec 20.

    PubMed 23264589

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VRX496 in people with HIV, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of serious adverse events & dose related toxicity. (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00295477, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2019.

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