VGX-3100 Delivered Intramuscularly (IM) Followed by Electroporation (EP) for the Treatment of HPV-16 and/or HPV-18 Related Anal or Anal/Peri-Anal, High Grade Squamous Intraepithelial Lesion (HSIL) in Individuals Seronegative for Human Immunodeficiency Virus (HIV)-1/2
VGX-3100 Delivered Intramuscularly (IM) Followed by Electroporation (EP) for the Treatment of HPV-16 and/or HPV-18 Related Anal or Anal/Peri-Anal, High Grade Squamous Intraepithelial Lesion (HSIL) in Individuals Seronegative for Human Immunodeficiency Virus (HIV)-1/2
This is a phase 2, open-label efficacy study of VGX-3100 administered by intramuscular (IM)
 injection followed by electroporation (EP) in adult men and women who are human
 immunodeficiency virus (HIV) negative with histologically confirmed anal or anal/peri-anal
 high-grade squamous intraepithelial lesion (HSIL) associated with human papilloma virus
 (HPV)-16 and/or HPV-18. Approximately 24 participants will receive at least 3 doses of
 VGX-3100.
Inclusion Criteria:

 -  Negative screening test for HIV-1/2 within 30 days of Dose 1;

 -  Confirmed anal or anal/peri-anal HPV-16/18 infection at Screening by polymerase chain
 reaction (PCR) from HSIL specimen;

 -  Anal tissue specimen/slides for diagnosis must be collected within 10 weeks of first
 dose of VGX-3100;

 -  At least one anal or anal/peri-anal (AIN2/3 and/or PAIN2/PAIN3) lesion that is
 histologically-confirmed as HSIL at Screening;

 -  Appropriate candidate for histology collection procedures (i.e. excision or biopsy) as
 judged by the Investigator;

 -  Female subjects must be post-menopausal, surgically sterile or agree to avoid
 pregnancy by continued abstinence or use of a contraceptive method with failure rate
 of less than 1% per year from Screening to one month after last dose of study
 medication (Week 12 or Week 40)

 -  Men who could father a child must agree to use at least one form of birth control
 during or continued abstinence from heterosexual intercourse prior to the study, for
 the duration of study participation and one month after last dose of study medication.

 -  Normal Screening electrocardiogram (ECG).

 Exclusion Criteria:

 -  Untreated micro invasive or invasive cancer;

 -  Biopsy-proven Vaginal Intraepithelial Neoplasia (VAIN) and not undergoing medical care
 and/or treatment for VAIN;

 -  Biopsy-proven Vulvar Intraepithelial Neoplasia (VIN) and not undergoing medical care
 and/or treatment for VIN;

 -  Biopsy-proven Cervical Intraepithelial Neoplasia (CIN) 2/3 and not undergoing medical
 care and/or treatment for CIN;

 -  Biopsy-proven Penile Intraepithelial Neoplasia (PIN) and not undergoing medical care
 and/or treatment for PIN;

 -  Anal or anal/peri-anal HSIL that is not accessible for sampling by biopsy instrument;

 -  Intra-anal and/or peri-anal lesion(s) that cannot be fully visualized at Screening;

 -  Inability to have complete and satisfactory high resolution anoscopic exams (HRAs)

 -  Any treatment for anal or anal/peri-anal HSIL (e.g. surgery) within 4 weeks of
 Screening;

 -  Pregnant, breast feeding or considering becoming pregnant within one month following
 the last dose of study medication;

 -  Presence of any abnormal clinical laboratory values greater than Grade 1 per Common
 Toxicity Criteria for Adverse Events (CTCAE) version 4.03 within 45 days prior to Day
 0 or less than Grade 1 but deemed clinically significant by the Investigator;

 -  Immunosuppression as a result of underlying illness or treatment;

 -  History of previous therapeutic HPV vaccination;

 -  Receipt of any non-study related non-live vaccine within 2 weeks of any VGX-3100 dose;

 -  Receipt of any non-study related live vaccine (e.g. measles vaccine) within 4 weeks of
 any VGX-3100 dose;

 -  Significant acute or chronic medical illness that could be negatively impacted by the
 electroporation treated as deemed by the Investigator;

 -  Current or history of clinically significant, medically unstable disease which, in the
 judgment of the investigator, would jeopardize the safety of the subject, interfere
 with study assessments or endpoint evaluation, or otherwise impact the validity of the
 study results;

 -  Prior major surgery within 4 weeks of Day 0;

 -  Participation in an interventional study with an investigational compound or device
 within 4 weeks of signing the ICF;

 -  Any illness or condition that in the opinion of the Investigator may affect the safety
 of the subject or the evaluation of any study endpoint.