Single DermaVir Immunization in HIV-1 Infected Patients on HAART (GIHU004)

February 19, 2013 updated by: Genetic Immunity

A Phase I Study to Evaluate the Tolerability and Safety of LC002, a DermaVir Vaccine, in HIV-1-infected Subjects Currently Under Treatment With Highly Active Antiretroviral Therapy (HAART)

  • DermaVir is a plasmid DNA-containing synthetic nanomedicine. It is administered topically with DermaPrep to target Langerhans cells. Langerhans cells with DermaVir migrate to lymph nodes and express HIV-like particles that induce immune responses to kill HIV-infected cells.
  • Hypothesis: Single DermaVir immunization is safe and immunogenic measured by induction of HIV-specific precursor/memory T cell responses.
  • GIHU004 was a phase I dose escalation study conducted in Hungary. It evaluated the safety and immunogenicity of three dosing regimens of topical DermaVir immunization for the treatment of HIV-infected individuals on fully suppressive highly active antiretroviral therapy (HAART).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study enrolled nine HIV-infected adult subjects in three sequential dose cohorts. All had durable suppression of HIV-RNA on HAART over the previous 6 months and CD4 count over 300 cells/mm3. Subjects, received on study Day 0 a single DermaVir immunization:

  • Low dose: 0.1 mg pDNA, 0.8 mL DermaVir administered under two DermaPrep patches.
  • Medium dose: 0.4 mg pDNA, 3.2 mL DermaVir administered under four DermaPrep patches.
  • High dose: 0.8 mg pDNA, 6.4 mL DermaVir administered under eight DermaPrep patches.

Subjects were on study for a total of 28 days followed by a post-treatment safety follow-up for 48 weeks. HAART was not interrupted. All subjects completed the 28-day treatment and 48 weeks safety follow up phase.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hungary
      • Budapest, Hungary, 1097
        • Saint Laszlo Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability and willingness of subject or legal guardian/representative to give written informed consent
  • HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA
  • On a stable antiretroviral regimen without changes or interruptions for at least 12 weeks prior to study entry
  • Plasma HIV-1 RNA level of less than 50 copies/mL, obtained at least twice within the 12 weeks prior to study entry
  • Peak plasma HIV-1 RNA level before initiation of HAART > 1000 copies/mL
  • CD4 cell count > 300 cells/mm3 within the 12 weeks prior to study entry
  • Nadir (lowest) CD4+ cell count > 250 cells/mm3 at any time prior to study entry

  • The following laboratory values, obtained within 30 days prior to study entry:

    • Absolute neutrophil count (ANC) > 1000/mm3
    • Hemoglobin > 9.0 g/dL
    • Platelet count > 50,000/mm3
    • Serum creatinine < upper limit of the laboratory normal range (ULN)
    • AST (SGOT), ALT (SGPT), and alkaline phosphatase < 2.5 x ULN
    • Total bilirubin < 2.5 x ULN
    • Anti-nuclear antibody (ANA) titer of 1:40 or lower and negative for serum anti-double-stranded DNA antibody (anti-ds-DNA) test result at screening.
  • All women of reproductive potential must have a negative urine beta-HCG pregnancy test performed within 14 days prior to study entry.
  • Female study volunteers who are not of reproductive potential or whose male partner has undergone successful vasectomy are eligible without requiring the use of contraception. Acceptable documentation of menopause, sterilization, and azoospermia is written or oral documentation communicated by clinician.
  • All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization) and, if participating in sexual activity that could lead to pregnancy, the study volunteer/ partner must use two reliable methods of contraception simultaneously while receiving the protocol-specified vaccination and for 3 months after the last vaccination.
  • Karnofsky performance score > 90 within 30 days prior to study entry
  • Men and women age 18-50 years

Exclusion Criteria:

  • Viral load measurement > 50 copies/mL within the last 12 weeks prior to study entry
  • History of or evidence of active skin disease (e.g. atopic dermatitis), chronic autoimmune disease or any other significant active skin disease
  • Treatment with topical corticosteroids in close proximity to the proposed vaccination sites within 2 weeks prior to study entry
  • Excessive exposure to the sun (e.g. sunbathing) within 2 weeks prior to study entry
  • Use of any local skin treatments to the targeted vaccination sites within 7 days prior to study entry
  • History of diabetes and bleeding disorders
  • Previous CDC category C event
  • Pregnancy or breast-feeding
  • Use of immunomodulating therapy, including cyclosporin, IgG-containing products, interleukins, interferons, systemic glucocorticosteroids, or exposure to an experimental HIV vaccine within 6 months prior to study entry
  • Receipt of any vaccine within 30 days prior to study entry
  • Allergy/sensitivity to study vaccine products, including adhesives, will be excluded
  • Active drug or alcohol use or dependence
  • Serious illness until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 14 days prior to study entry
  • Hepatitis B surface antigen and/or anti-hepatitis C positive

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1

Single low-dose DermaVir immunization

  • 0.1 mg pDNA/subject, 0.8 mL total volume of DermaVir
  • Administered topically with DermaPrep under two skin patches (0.4 mL/patch)
Biological: DermaVir
DermaVir is a synthetic pathogen-like nanomedicine. The active pharmaceutical ingredient is a plasmid DNA expressing fifteen HIV proteins that assemble into HIV-like particles. These particles are safe, cannot replicate, integrate or reverse transcribed. DermaVir is targeted to Langerhans cells with DermaPrep medical device. These DermaVir-containing Langerhans cells migrate to the lymph nodes, where induce HIV-specific cytotoxic T cells that can recognize and kill HIV-infected cells.
Other Names:
  • LC002
Drug: HAART
Three or more antiretroviral drugs that can fully suppress HIV RNA
Other Names:
  • Highly active antiretroviral therapy
Experimental: 2

Single medium-dose DermaVir immunization

  • 0.4 mg pDNA/subject, 3.2 mL total volume of DermaVir
  • Administered topically with DermaPrep under four skin patches (0.8 mL/patch)
Biological: DermaVir
DermaVir is a synthetic pathogen-like nanomedicine. The active pharmaceutical ingredient is a plasmid DNA expressing fifteen HIV proteins that assemble into HIV-like particles. These particles are safe, cannot replicate, integrate or reverse transcribed. DermaVir is targeted to Langerhans cells with DermaPrep medical device. These DermaVir-containing Langerhans cells migrate to the lymph nodes, where induce HIV-specific cytotoxic T cells that can recognize and kill HIV-infected cells.
Other Names:
  • LC002
Drug: HAART
Three or more antiretroviral drugs that can fully suppress HIV RNA
Other Names:
  • Highly active antiretroviral therapy
Experimental: 3

Single high-dose DermaVir immunization

  • 0.8 mg pDNA/subject, 6.4 mL total volume of DermaVir
  • Administered topically with DermaPrep under eight skin patches (0.4 mL/patch)
Biological: DermaVir
DermaVir is a synthetic pathogen-like nanomedicine. The active pharmaceutical ingredient is a plasmid DNA expressing fifteen HIV proteins that assemble into HIV-like particles. These particles are safe, cannot replicate, integrate or reverse transcribed. DermaVir is targeted to Langerhans cells with DermaPrep medical device. These DermaVir-containing Langerhans cells migrate to the lymph nodes, where induce HIV-specific cytotoxic T cells that can recognize and kill HIV-infected cells.
Other Names:
  • LC002
Drug: HAART
Three or more antiretroviral drugs that can fully suppress HIV RNA
Other Names:
  • Highly active antiretroviral therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Grade 3 Adverse Event Related to DermaVir Treatment
Time Frame: 28 days
Occurrence of at least one grade 3 or higher adverse event including signs/symptoms, laboratory toxicities and clinical events possibly, probably or definitely related to study treatment as judged by the Principal Investigator or the site investigators during the 28 days after DermaVir administration.
28 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CD4+ T Cell Counts/mm3
Time Frame: 28 days
28 days
Number of Subjects With Detectable Anti-ds Antibody and ANA
Time Frame: 28 days
28 days
Number of Subjects Having More Than 50 Copies/mL HIV RNA
Time Frame: 28 days
28 days
Change in HIV-specific Memory T Cell Responses at Day 28 Compare to Baseline
Time Frame: 28 days
HIV-specific T cell precursors with high proliferative capacity (PHPC) were quantified as described earlier [Calarota et al. J Immunol 2008]. Gag-, Tat- and Rev-specific T cells were measured representing ca. 25% of HIV epitopes included in DermaVir.
28 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in HIV-specific Memory T Cell Responses at Week 48
Time Frame: 48 weeks

HIV-specific T cell precursors with high proliferative capacity (PHPC) were quantified as described earlier [Calarota et al. J Immunol 2008]. Gag-, Tat- and Rev-specific T cells were measured representing ca. 25% of HIV epitopes included in DermaVir.

Note, group Single low-dose was measured at 24 weeks, for this group the 48 weeks data is not available
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genetic Immunity

Investigators

  • Principal Investigator: Denes Banhegyi, MD, Saint Laszlo Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2005

Primary Completion (Actual)

June 1, 2006

Study Completion (Actual)

June 1, 2006

Study Registration Dates

First Submitted

July 4, 2008

First Submitted That Met QC Criteria

July 8, 2008

First Posted (Estimate)

July 10, 2008

Study Record Updates

Last Update Posted (Estimate)

March 26, 2013

Last Update Submitted That Met QC Criteria

February 19, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GIHU004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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