A Follow-On Study With an H5 Influenza Vaccine for Subjects Who Participated in Study FLU-001
DNA vaccines consist of small pieces of DNA also known as plasmids, and have several potential advantages over traditional vaccines. Thus far, DNA vaccines appear to be well tolerated in humans. The investigators have developed a DNA vaccine, INO-3401, which includes plasmids targeting the proteins of the H5N1 avian influenza virus. The vaccine will be delivered via electroporation (EP) which uses the CELLECTRA constant current device to deliver a small electric charge following injection, since animal studies have shown that this delivery method increases the immune response to vaccine. The vaccine will be given to up 30 healthy adult subjects who have participated in study FLU-001. It is hypothesized that a booster dose with INO-3401 + EP will be well tolerated and immunogenic.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
|Official Title:||PHASE I, OPEN-LABEL, SAFETY, TOLERABILITY, AND IMMUNOGENICITY STUDY OF AN H5 INFLUENZA PLASMID VACCINE (INO-3401) IN HEALTHY ADULTS PREVIOUSLY VACCINATED WITH VGX-3400X|
- Safety [ Time Frame: Day 0 through Month 9 ] [ Designated as safety issue: Yes ]Frequency and severity of local and systemic reactogenicity, signs and symptoms, adverse events and serious adverse events.
- Humoral and cellular immune responses [ Time Frame: Day 0 through Month 9 ] [ Designated as safety issue: No ]Magnitude and frequency of antibody and cell-mediated immune responses to influenza proteins.
- Tolerability [ Time Frame: Day 0 and Month 3 ] [ Designated as safety issue: No ]Tolerability by Visual Analog Scale (VAS)
|Study Start Date:||May 2011|
|Study Completion Date:||August 2012|
|Primary Completion Date:||August 2012 (Final data collection date for primary outcome measure)|
Experimental: All subjects
All subjects will receive 0.9mg/mL of study vaccine (INO-3401 DNA plasmid vaccine) at Day o and Month 3.
Biological: INO-3401 + EP
All subjects will receive 0.9mg/mL of study vaccine (INO-3401 DNA plasmid vaccine)at Day 0 and Month 3.
The use of DNA plasmids containing genes that express viral antigens may be a promising way to formulate a vaccine that can effectively prevent infection and disease caused by the H5N1 avian influenza virus. Plasmid vectors are simple to construct and are easy to manufacture at a relatively low cost. Vaccination with plasmids that express influenza proteins should induce the development of serum antibodies and might also induce significant quantities of secretory IgA antibodies and/or CMI. The DNA sequences included in the vaccine could also result in the proliferation of T lymphocytes that could broaden the effectiveness of the vaccine to include variant strains of H5N1 with antigenically modified HA (i.e., drifted strains).
Electroporation (EP) is a technology in which a transmembrane electrical field is applied to increase the permeability of cell membranes to create microscopic pathways (pores) and thereby enhance the uptake of drugs, vaccines, or other agents into target cells. Their presence allows macromolecules, ions, and water to pass from one side of the membrane to the other. The presence of a constant field influences the kinetics of directional translocation of the macromolecular plasmid, such that the plasmid delivery in vivo has been sufficient to achieve physiological levels of secreted proteins. Intradermal (ID) injection of plasmid followed by EP has been used very successfully to deliver therapeutic genes that encode for a variety of hormones, cytokines, or enzymes in a variety of species. EP is currently being used in humans to deliver cancer vaccines and therapeutics as well as in gene therapy. The expression levels are increased by as much as 3 orders of magnitude over plasmid injection alone.
The use of EP via the CELLECTRA® device should increase the expression of H5N1 influenza virus genes in the INO-3401 DNA vaccine.
|United States, Kansas|
|Vince and Associates Clinical Research|
|Overland Park, Kansas, United States|
|United States, Maryland|
|Rockville, Maryland, United States|
|Study Director:||Mark Bagarazzi, MD||Inovio Pharmaceuticals|