Single DermaVir Immunization in HIV-1 Infected Patients on HAART

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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)

Conditions
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HIV Infection

Intervention / Treatment
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* Biological: DermaVir
* Drug: HAART


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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<br>* 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.<br>* Other names: LC002;Drug: HAART<br>* Three or more antiretroviral drugs that can fully suppress HIV RNA<br>* Other names: Highly active antiretroviral therapy;|
| Experimental: 2<br>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<br>* 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.<br>* Other names: LC002;Drug: HAART<br>* Three or more antiretroviral drugs that can fully suppress HIV RNA<br>* Other names: Highly active antiretroviral therapy;|
| Experimental: 3<br>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<br>* 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.<br>* Other names: LC002;Drug: HAART<br>* Three or more antiretroviral drugs that can fully suppress HIV RNA<br>* Other names: Highly active antiretroviral therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 3 Adverse Event Related to DermaVir Treatment | 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 |  | 28 days | 
| Number of Subjects With Detectable Anti-ds Antibody and ANA |  | 28 days | 
| Number of Subjects Having More Than 50 Copies/mL HIV RNA |  | 28 days | 
| Change in HIV-specific Memory T Cell Responses at Day 28 Compare to Baseline | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Vaccine, Immune Therapy, DermaVir