Single DermaVir Immunization in HIV-1 Infected Patients on HAART

NCT00712530 | Completed Phase 1 Results DMC

• 1 other identifier: GIHU004
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

HIV Infection

Keywords

HIV; Vaccine; Immune Therapy; DermaVir

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  28 days

Other Outcomes (1)

• Change in HIV-specific Memory T Cell Responses at Week 48

  48 weeks

Study Arms (3)

1

EXPERIMENTAL

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; Drug: HAART

2

EXPERIMENTAL

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; Drug: HAART

3

EXPERIMENTAL

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; Drug: HAART

Interventions

DermaVir BIOLOGICAL

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.

Also known as: LC002

1; 2; 3

HAART DRUG

Three or more antiretroviral drugs that can fully suppress HIV RNA

Also known as: Highly active antiretroviral therapy

1; 2; 3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Genetic Immunity: lead

Study Sites (1)

Saint Laszlo Hospital

Budapest, Budapest, 1097, Hungary

Location

Related Publications (6)

• 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.

  PMID: 21839051 BACKGROUND

• 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.

  PMID: 21109034 BACKGROUND

• 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.

  PMID: 20347027 BACKGROUND

• 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. doi: 10.4049/jimmunol.180.9.5907.

  PMID: 18424710 BACKGROUND

• 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.

  PMID: 22590502 RESULT

• 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.

  PMID: 22659241 RESULT

Related Links

• Genetic Immunity's homepage

MeSH Terms

Conditions

HIV Infections

Interventions

DermaVir; Antiretroviral Therapy, Highly Active

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Drug Therapy, Combination; Drug Therapy; Therapeutics

Limitations and Caveats

This is a Phase I small sample study that was not powered for the secondary efficacy endpoints.

Results Point of Contact

• Title: Dr. Denes Banhegyi
• Organization: Szent Laszlo Hospital, Budapest, Hungary

immunol@mail.datanet.hu

+3614558152

Study Officials

• Denes Banhegyi, MD

  Saint Laszlo Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 4, 2008
• First Posted: July 10, 2008
• Study Start: January 1, 2005
• Primary Completion: June 1, 2006
• Study Completion: June 1, 2006
• Last Updated: March 26, 2013
• Results First Posted: March 26, 2013

Record last verified: 2013-02

Locations

HU (1)