Single DermaVir Immunization in HIV-1 Infected Patients on HAART

HIV Infection Clinical Trial

— GIHU004  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00712530
• Other study ID #: GIHU004
• Status: Completed
• Phase: Phase 1
• First received: July 4, 2008
• Last updated: February 19, 2013
• Start date: January 2005
• Est. completion date: June 2006

Study information

• Verified date: February 2013
• Source: Genetic Immunity
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hungary: National Institute of Pharmacy
• Study type: Interventional

Clinical Trial Summary

• 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: June 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

Intervention

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.

Drug:
• HAART
Three or more antiretroviral drugs that can fully suppress HIV RNA

Locations

Country	Name	City	State
Hungary	Saint Laszlo Hospital	Budapest

Sponsors (1)

Lead Sponsor	Collaborator
Genetic Immunity

Country where clinical trial is conducted

Hungary, 

References & Publications (6)

Calarota SA, Foli A, Maserati R, Baldanti F, Paolucci S, Young MA, Tsoukas CM, Lisziewicz J, Lori F. HIV-1-specific T cell precursors with high proliferative capacity correlate with low viremia and high CD4 counts in untreated individuals. J Immunol. 2008 May 1;180(9):5907-15. — View Citation

Lisziewicz J, Bakare N, Calarota SA, Bánhegyi D, Szlávik J, Ujhelyi E, Toke ER, Molnár 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 individ — View Citation

Lisziewicz J, Toke ER. Nanomedicine applications towards the cure of HIV. Nanomedicine. 2013 Jan;9(1):28-38. doi: 10.1016/j.nano.2012.05.012. Epub 2012 May 30. Review. — View Citation

Lorincz O, Toke ER, Somogyi E, Horkay F, Chandran PL, Douglas JF, Szebeni J, Lisziewicz J. Structure and biological activity of pathogen-like synthetic nanomedicines. Nanomedicine. 2012 May;8(4):497-506. doi: 10.1016/j.nano.2011.07.013. Epub 2011 Aug 10. — View Citation

Somogyi E, Xu J, Gudics A, Tóth J, Kovács 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. — View Citation

Toke ER, Lorincz O, Somogyi E, Lisziewicz J. Rational development of a stable liquid formulation for nanomedicine products. Int J Pharm. 2010 Jun 15;392(1-2):261-7. doi: 10.1016/j.ijpharm.2010.03.048. Epub 2010 Mar 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in HIV-specific Memory T Cell Responses at Week 48	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	No
Primary	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	Yes
Secondary	CD4+ T Cell Counts/mm3		28 days	Yes
Secondary	Number of Subjects With Detectable Anti-ds Antibody and ANA		28 days	Yes
Secondary	Number of Subjects Having More Than 50 Copies/mL HIV RNA		28 days	Yes
Secondary	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	No

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