Repeated DermaVir Immunizations in HIV-1 Infected Treatment-naïve Patients

HIV Infection Clinical Trial

— GIEU006  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00711230
• Other study ID #: DermaVir Phase II
• Secondary ID: 2007-001955-20
• Status: Completed
• Phase: Phase 2
• Start date: April 2008
• Est. completion date: January 1, 2015

Study information

• Verified date: January 2020
• Source: Genetic Immunity
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: January 1, 2015
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

Biological:
• DermaVir

• Placebo
glucose/dextrose

Locations

Country	Name	City	State
Germany	ICH Grindel	Hamburg
Germany	ifi-Medizin GmbH at the Asklepios Klinik St. Georg	Hamburg
Germany	University Medical Center Hamburg-Eppendorf	Hamburg

Sponsors (2)

Lead Sponsor	Collaborator
Genetic Immunity	Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

References & Publications (10)

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. Epub 2007 Jan 22. — 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 individuals. PLoS One. 2012;7(5):e35416. doi: 10.1371/journal.pone.0035416. Epub 2012 May 9. — 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

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. — View Citation

Lisziewicz J, Trocio J, Xu J, Whitman L, Ryder A, Bakare N, Lewis MG, Wagner W, Pistorio A, Arya S, Lori F. Control of viral rebound through therapeutic immunization with DermaVir. AIDS. 2005 Jan 3;19(1):35-43. — View 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. — View Citation

Lori F. DermaVir: a plasmid DNA-based nanomedicine therapeutic vaccine for the treatment of HIV/AIDS. Expert Rev Vaccines. 2011 Oct;10(10):1371-84. doi: 10.1586/erv.11.118. — 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
Primary	Percent of participants with primary safety endpoint	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.	24 weeks
Secondary	HIV-1 RNA		24 weeks
Secondary	CD4+ and CD8+ T-cell counts		24 weeks
Secondary	HIV-specific memory T cell responses	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)	24 weeks

External Links

•   DermaVir for initial treatment of HIV-infected subjects demonstrates preliminary safety, immunogenicity and HIV-RNA reduction versus placebo immunization
•   Genetic Immunity's homepage