Study of VGX-3400X, H5N1 Avian Influenza Virus DNA Plasmid + Electroporation in Healthy Adults
Phase I, Open-label, Dose Escalation Study to Evaluate the Safety, Tolerability, and Immunogenicity in Healthy Adults of a DNA Plasmid Vaccine for H5 Avian Influenza (VGX-3400X) Administered by Intramuscular (IM) Injection Followed by Electroporation (EP)
Study Overview
Detailed Description
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. IM 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 VGX-3400X DNA vaccine.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Kansas
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Overland Park, Kansas, United States, 66212
- Vince & Associates
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Maryland
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Rockville, Maryland, United States, 20850
- Accelovance
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Written informed consent in accordance with institutional guidelines. If required by local law, candidates must also authorize the release and use of protected health information (PHI);
- Adults of either gender 18-50 years of age;
- Healthy subjects as judged by the Investigator;
- Current nonsmoker;
- Body mass index (BMI) ≤30 kg/m^2
- Women of child-bearing potential (WOCBP) agree to remain sexually abstinent, use medically effective contraception or have a partner who is sterile for the duration of the study (7 months);
- Able and willing to comply with all study procedures.
Exclusion Criteria:
- Positive serological test for HIV, hepatitis C virus or hepatitis B virus surface antigen (HBsAg);
- Pregnant or breastfeeding subjects;
- Any concurrent condition requiring the continued use of systemic or topical steroids at or near the injection site or the use of immunosuppressive agents. All other corticosteroids must be discontinued > 4 weeks prior to Day 0 of study vaccine administration;
- Administration of any blood product within 3 months of enrollment;
- Prior receipt of an H5N1 influenza vaccine at any time;
- Subjects with a contraindication to influenza vaccination other than egg allergy (such as Guillain-Barre Syndrome after receiving influenza vaccination);
- Administration of any vaccine within 6 weeks of enrollment;
- Subject is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent;
- Subjects with cardiac pre-excitation syndromes (such as Wolff-Parkinson- White);
- Subjects with a history of seizures (unless seizure free for 5 years);
- Subjects with tattoos, scars, or active lesions/rashes within 2 cm of the site of vaccination/EP;
- Subjects with any implantable leads;
- Active drug or alcohol use or dependence;
- Prisoners or subjects who are compulsorily detained;
- Any other conditions judged by the investigator that would limit the evaluation of a subject.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: PREVENTION
- Allocation: NON_RANDOMIZED
- Interventional Model: PARALLEL
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: 0.6mg of DNA/dose
Subjects will receive a 2 dose series of VGX-3400X containing 0.6 mg DNA/dose administered via IM injection + electroporation at Day 0 and Month 1
|
DNA plasmids delivered via IM injection + electroporation using CELLECTRA device
|
|
EXPERIMENTAL: 2mg DNA/dose
Subjects will receive a 2 dose series of VGX-3400X containing 2mg of DNA/dose administered via IM injection + electroporation at Day 0 and Month 1
|
DNA plasmids delivered via IM injection + electroporation using CELLECTRA device
|
|
EXPERIMENTAL: 6mg DNA/dose
Subjects will receive a 2 dose series of VGX-3400X containing 6 mg DNA/dose administered via IM injection + electroporation at Day 0 and Month 1
|
DNA plasmids delivered via IM injection + electroporation using CELLECTRA device
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Safety and tolerability
Time Frame: Day 0 through Month 12
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Frequency and severity of local and systemic reactogenicity signs and symptoms, adverse events and serious adverse events.
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Day 0 through Month 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Humoral and cellular immune responses
Time Frame: Day 0 through Month 12
|
Magnitude and frequency of antibody and cell-mediated immune responses to influenza proteins.
|
Day 0 through Month 12
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Steven Hull, MD, Vince & Associates
- Principal Investigator: Rita Ghosh, MD, Accelovance
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- FLU-001
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