Repeated DermaVir Immunizations in HIV-1 Infected Treatment-naïve Patients (GIEU006)

A Phase II Randomized, Placebo-Controlled, Multi-Center Study to Evaluate the Safety, Tolerability, Immunogenicity, and Antiretroviral Activity of DermaVir Patch (LC002) in Treatment-Naïve HIV-1-Infected Patients

DermaVir is a synthetic pathogen-like nanomedicine. The active pharmaceutical ingredient is a single plasmid DNA expressing fifteen HIV antigens that assemble to HIV-like particles. These particles are safe; replication, integration and reverse transcription deficient. DermaVir is targeted to Langerhans cells by topical administration with DermaPrep. Langerhans cells with DermaVir migrate to lymph nodes and induce HIV-specific T cells that can kill HIV-infected cells. GIEU006 is a Phase II randomized, placebo-controlled, dose-finding, double-blinded, multicenter study to assess the safety, tolerability, immunogenicity, and preliminary antiretroviral activity of DermaVir in antiretroviral therapy naïve adults with HIV-infection.

Patients were randomized into one of the following 6 arms: Arm 1: Low dose DermaVir (0.2 mg DNA in 2 DermaPrep patches, n=9) Arm 2: Low dose Placebo (2 DermaPrep patches, n=3) Arm 3: Medium dose DermaVir (0.4 mg DNA in 4 DermaPrep patches, n=9) Arm 4: Medium dose Placebo (4 DermaPrep patches, n=3) Arm 5: High dose DermaVir (0.8 mg DNA in 8 DermaPrep patches, n=9) Arm 6: High dose Placebo (8 DermaPrep patches, n=3) DermaPrep Patch size: 80 cm2. DermaVir Standard Unit per patch is 0.1 mg DNA = 0.8 mL of DermaVir nanomedicine. The patch sites for immunization are preferably the left or right upper back and left or right upper ventral thigh. The same skin sites should be used for all immunizations. Immunization schedule (Days): 0, 42, 84, and 126. The total DermaVir dose: Low dose: 0.8 mg DNA Medium dose: 1.6 mg DNA High Dose: 3.2 mg DNA DermaVir immunizations were administered over an 18-week period Primary endpoint: 24 weeks Safety follow up: 234 weeks

Dosage: 0.2 mg DNA Dosage form: 1.6 mL DNA/PEIm nanomedicine Administration with 2 DermaPrep patches Frequency: every six weeks Duration: 18 weeks (4 DermaVir treatments)

Dosage form: 1.6 mL Placebo Administration with 2 DermaPrep patches Frequency: every six weeks Duration: 18 weeks (4 Placebo treatments)

Dosage: 0.4 mg DNA Dosage form: 3.2 mL DNA/PEIm nanomedicine Administration with 4 DermaPrep patches Frequency: every six weeks Duration: 18 weeks (4 DermaVir treatments)

Dosage form: 1.6 mL Placebo Administration with 4 DermaPrep patches Frequency: every six weeks Duration: 18 weeks (4 Placebo treatments)

Dosage: 0.8 mg DNA Dosage form: 6.4 mL DNA/PEIm nanomedicine Administration with 8 DermaPrep patches Frequency: every six weeks Duration: 18 weeks (4 DermaVir treatments)

Dosage form: 6.4 mL Placebo Administration with 8 DermaPrep patches Frequency: every six weeks Duration: 18 weeks (4 Placebo treatments)

Primary safety endpoint: occurrence of at least two > Grade 3 adverse event including signs/symptoms, lab toxicities, and/or clinical events that is possibly or definitely related to study treatment (as judged by the GIEU006 team, including site clinicians on the team, blinded to treatment arm) any time from the first day of study treatment until 42 days after the last study vaccine administration.

Measured with Precursors with High Proliferative Capacity (PHPC) assay (Calarota et al. HIV-1-Specific T cell precursors with high proliferative capacity correlate with low viremia and high CD4 counts in untreated individuals. J Immunol 2008;180:5907-15)

Main inclusion Criteria: HIV antibody positive Plasma HIV RNA value ≥5,000 copies/mL and ≤ 150,000 c/mL Antiretroviral therapy naïve Documented CD4+ T-cell count at screening ≥400 cells/mm3 Main exclusion Criteria: No skin disease No tattoos, or changes in pigmentation at the selected skin immunization sites No acute or chronic illness (e.g Hepatitis C) No chronic autoimmune diseases No treatment with any immune modulating agents

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DermaVir for initial treatment of HIV-infected subjects demonstrates preliminary safety, immunogenicity and HIV-RNA reduction versus placebo immunization