Phase I of Human Papillomavirus (HPV) DNA Plasmid (VGX-3100) + Electroporation for CIN 2 or 3

Study Overview
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Brief Summary
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DNA vaccines, which are small pieces of DNA also known as plasmids, have several advantages over traditional vaccines such as live attenuated virus and recombinant protein-based vaccines. DNA vaccines appear to be well tolerated in humans. Therefore, we have developed our DNA vaccine, VGX-3100, to include plasmids targeting E6 and E7 proteins of both HPV subtypes 16 and 18. We have chosen to deliver our candidate vaccines via electroporation (EP) using the CELLECTRA™ constant current device to deliver a small electric charge following intramuscular (IM) injection, since animal studies have shown that this delivery method increases the immune response to our DNA vaccine leading to a decrease in the size of tumors caused by HPV 16 and 18. The vaccine is proposed to be given to patients with a history of CIN 2 and 3 that have been treated by surgery. We will determine which dose the DNA vaccine will be the best tolerated and elicit the strongest immune response.

Official Title
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Phase I Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Immunogenicity of Human Papillomavirus (HPV) DNA Plasmid (VGX-3100) + Electroporation (EP) in Adult Females Post Surgical or Ablative Treatment of Grade 2 or 3 Cervical Intraepithelial Neoplasia (CIN)

Conditions
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Papillomavirus Infections

Intervention / Treatment
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* Biological: VGX-3100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent in accordance with institutional guidelines; Female 18-45 years of age; Post surgical (including LEEP and conization) or ablative treatment and a diagnosis of CIN 2 or 3, while under physician care as per ASCCP guidelines (Appendix D); Normal ECG and normal laboratory values as judged by Grade 0-1 as per Toxicity Grading Scale for Healthy Adults (Appendix C) for CBC, CPK, SMA-12 and urinalysis evaluations done up to 30 days prior to administration of study treatment; Body mass index (BMI) ≤30 kg/m2; Women of child-bearing potential (WOCBP) agree to remain sexually abstinent, use medically effective contraception (oral contraception, barrier methods, spermicide, etc), or have a partner who is sterile (i.e., vasectomy) from enrollment to 3 months after the last injection ( 6 months); Able and willing to comply with all study procedures. Exclusion Criteria: Active infection with herpes simplex virus (HSV); Positive serological test for HIV virus, 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 (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents. All other corticosteroids must be discontinued > 4 weeks prior to Day 1 of treatment;; Administration of any blood product within 3 months of enrollment; Administration of any vaccine within 6 weeks of enrollment; Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent; Metal implants at the site of injection; Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements; Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e. infections disease) illness must not be enrolled into this study; Any other conditions judged by the investigator that would limit the evaluation of a subject.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.6mg of DNA/dose<br>Subjects will receive a 3 dose series of VGX-3100 containing 0.6mg DNA/dose administered via IM injection + electroporation at Day 0, Month 1 and Month 3 | Biological: VGX-3100<br>* DNA plasmid delivered via IM injection + electroporation using CELLECTRA device<br>|
| Experimental: 2mg of DNA/dose<br>Subjects will receive a 3 dose series of VGX-3100 containing 2mg of DNA/dose administered via IM injection + electroporation at Day 0, Month 1 and Month 3 | Biological: VGX-3100<br>* DNA plasmid delivered via IM injection + electroporation using CELLECTRA device<br>|
| Experimental: 6mg of DNA/dose<br>Subjects will receive a 3 dose series of VGX-3100 containing 6mg DNA/dose administered via IM injection + electroporation at Day 0, Month 1 and Month 3 | Biological: VGX-3100<br>* DNA plasmid delivered via IM injection + electroporation using CELLECTRA device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of escalating doses of VGX-3100, administered by IM injection with EP to adult female subjects post surgical or ablative treatment of grade 2 or 3 CIN. |  | Through Month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral and cellular immune responses to VGX-3100 in blood samples obtained from study subjects after each dose of a 3-dose series of VGX-3100 containing 0.6, 2 or 6 mg of DNA/dose. |  | At end of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CIN 2 or 3, cervical cancer