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

• ClinicalTrials.gov Identifier: NCT00711230
• Recruitment Status: Completed
• First Posted: July 8, 2008
• Last Update Posted: January 28, 2020
• Sponsor: Genetic Immunity
• Collaborator: Universitätsklinikum Hamburg-Eppendorf
• Information provided by (Responsible Party): Genetic Immunity

Tracking Information

• First Submitted Date: July 4, 2008
• First Posted Date: July 8, 2008
• Last Update Posted Date: January 28, 2020
• Study Start Date: April 2008
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2013)

Percent of participants with primary safety endpoint [ Time Frame: 24 weeks ]

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.

• Original Primary Outcome Measures (submitted: July 7, 2008): Safety and tolerability of DermaVir Patch [ Time Frame: Throughout the study ]

Current Secondary Outcome Measures (submitted: February 7, 2013)

• HIV-1 RNA [ Time Frame: 24 weeks ]
• CD4+ and CD8+ T-cell counts [ Time Frame: 24 weeks ]
• HIV-specific memory T cell responses [ Time Frame: 24 weeks ]
  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)

Original Secondary Outcome Measures (submitted: July 7, 2008)

• HIV-1 RNA measurements to assess the antiretroviral activity of the DermaVir Patch [ Time Frame: Throughout the study ]
• Changes in CD4+ and CD8+ T-cell counts during DermaVir Patch treatment [ Time Frame: Throughout the study ]
• Immunogenicity of DermaVir Patch [ Time Frame: Throughout the study ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: HIV Infection

Intervention

• Biological: DermaVir
  Other Name: LC002
• Biological: Placebo
  glucose/dextrose

Study Arms

• Experimental: 1: Low dose DermaVir
  • 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)
  Intervention: Biological: DermaVir
• Experimental: 2: Low dose Placebo
  • Dosage form: 1.6 mL Placebo
  • Administration with 2 DermaPrep patches
  • Frequency: every six weeks
  • Duration: 18 weeks (4 Placebo treatments)
  Intervention: Biological: Placebo
• Experimental: 3: Medium dose DermaVir
  • 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)
  Intervention: Biological: DermaVir
• Experimental: 4: Medium dose Placebo
  • Dosage form: 1.6 mL Placebo
  • Administration with 4 DermaPrep patches
  • Frequency: every six weeks
  • Duration: 18 weeks (4 Placebo treatments)
  Intervention: Biological: Placebo
• Experimental: 5: High dose DermaVir
  • 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)
  Intervention: Biological: DermaVir
• Experimental: 6: High dose Placebo
  • Dosage form: 6.4 mL Placebo
  • Administration with 8 DermaPrep patches
  • Frequency: every six weeks
  • Duration: 18 weeks (4 Placebo treatments)
  Intervention: Biological: Placebo

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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. doi: 10.1097/00002030-200501030-00004.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 7, 2008): 36
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: January 1, 2015
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT00711230
• Other Study ID Numbers: DermaVir Phase II; 2007-001955-20 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Genetic Immunity
• Original Responsible Party: Julianna Lisziewicz, PhD, Genetic Immunity Kft.
• Current Study Sponsor: Genetic Immunity
• Original Study Sponsor: Same as current
• Collaborators: Universitätsklinikum Hamburg-Eppendorf

Investigators

• Principal Investigator: Jan Van Lunzen, PhD, MD; Universitätsklinikum Hamburg-Eppendorf

• PRS Account: Genetic Immunity
• Verification Date: January 2020