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

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)

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.

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.