Clinical trial NCT00711230: Repeated DermaVir Immunizations in HIV-1 Infected Treatment-naïve Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
Keywords: HIV
Vaccine
Immune Therapy
DermaVir
Lead sponsor: Genetic Immunity
Sponsor class: INDUSTRY
Collaborators: name: Universitätsklinikum Hamburg-Eppendorf
First posted: 2008-07-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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

Primary outcomes:
measure: Percent of participants with primary safety endpoint
timeFrame: 24 weeks
Secondary outcomes:
measure: HIV-1 RNA
timeFrame: 24 weeks
measure: CD4+ and CD8+ T-cell counts
timeFrame: 24 weeks
measure: HIV-specific memory T cell responses
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: ifi-Medizin GmbH at the Asklepios Klinik St. Georg
city: Hamburg
country: Germany
facility: ICH Grindel
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf
name: Jan Van Lunzen, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lisziewicz J, Bakare N, Calarota SA, Banhegyi D, Szlavik J, Ujhelyi E, Toke ER, Molnar L, Lisziewicz Z, Autran B, Lori F. Single DermaVir immunization: dose-dependent expansion of precursor/memory T cells against all HIV antigens in HIV-1 infected individuals. PLoS One. 2012;7(5):e35416. doi: 10.1371/journal.pone.0035416. Epub 2012 May 9.
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citation: Somogyi E, Xu J, Gudics A, Toth J, Kovacs AL, Lori F, Lisziewicz J. A plasmid DNA immunogen expressing fifteen protein antigens and complex virus-like particles (VLP+) mimicking naturally occurring HIV. Vaccine. 2011 Jan 17;29(4):744-53. doi: 10.1016/j.vaccine.2010.11.019. Epub 2010 Nov 23.
citation: Calarota SA, Weiner DB, Lori F, Lisziewicz J. Induction of HIV-specific memory T-cell responses by topical DermaVir vaccine. Vaccine. 2007 Apr 20;25(16):3070-4. doi: 10.1016/j.vaccine.2007.01.024. Epub 2007 Jan 22.
citation: Lisziewicz J, Trocio J, Whitman L, Varga G, Xu J, Bakare N, Erbacher P, Fox C, Woodward R, Markham P, Arya S, Behr JP, Lori F. DermaVir: a novel topical vaccine for HIV/AIDS. J Invest Dermatol. 2005 Jan;124(1):160-9. doi: 10.1111/j.0022-202X.2004.23535.x.
citation: Lori F, Trocio J, Bakare N, Kelly LM, Lisziewicz J. DermaVir, a novel HIV immunisation technology. Vaccine. 2005 Mar 18;23(17-18):2030-4. doi: 10.1016/j.vaccine.2005.01.004.
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