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

Sponsor

Genetic Immunity (Industry)

Overall Status

Completed

CT.gov ID

NCT00711230

Collaborator

Universitätsklinikum Hamburg-Eppendorf (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection	Biological: DermaVir Biological: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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 Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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)	Biological: DermaVir Other Names: LC002
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)	Biological: Placebo glucose/dextrose
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)	Biological: DermaVir Other Names: LC002
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)	Biological: Placebo glucose/dextrose
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)	Biological: DermaVir Other Names: LC002
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)	Biological: Placebo glucose/dextrose

Outcome Measures

Primary Outcome Measures

Percent of participants with primary safety endpoint [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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	ifi-Medizin GmbH at the Asklepios Klinik St. Georg	Hamburg	Germany	20099
2	ICH Grindel	Hamburg	Germany	20146
3	University Medical Center Hamburg-Eppendorf	Hamburg	Germany	20249