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
Condition: Anal Neoplasm
MeSH terms: Acquired Immunodeficiency Syndrome; HIV Infections; Squamous Intraepithelial Lesions of the Cervix; Carcinoma, Squamous Cell; Carcinoma in Situ; Anus Neoplasms
Intervention: VGX-3100; CELLECTRA™ 5PSP
Intervention description: One milliliter (1 mL) VGX-3100 (deoxyribonucleic acid [DNA] plasmids encoding E6 and E7 proteins of HPV types 16 and 18) will be injected IM and delivered by EP using CELLECTRA™ 5PSP on Day 0, Week 4 and Week 12, and potentially Week 40.; IM injection of VGX-3100 is followed by EP with the CELLECTRA™ 5PSP device.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: High-grade squamous intraepithelial lesions (HSIL); Human papillomavirus (HPV); HPV-16; HPV-18; Anal intraepithelial neoplasia 2 (AIN2); Anal intraepithelial neoplasia 3 (AIN3); Peri-anal intraepithelial neoplasia 2 (PAIN2); Peri-anal intraepithelial neoplasia 3 (PAIN3)

Summary:

      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.
    

Eligibility criteria:

        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.