REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)
Condition: Cervical Dysplasia; Cervical High Grade Squamous Intraepithelial Lesion; HSIL
MeSH terms: Uterine Cervical Dysplasia; Squamous Intraepithelial Lesions of the Cervix; Carcinoma, Squamous Cell; Carcinoma in Situ
Intervention: VGX-3100; Placebo; Electroporation (EP)
Intervention description: 1 mL VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.; 1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.; Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 201.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Cervical intraepithelial neoplasia (CIN); Human papillomavirus (HPV); High grade squamous intraepithelial lesion (HSIL); CIN 2; CIN 3; papillomavirus

Summary:

      HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to
      determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular
      (IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women
      with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL)
      (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) associated with human
      papillomavirus (HPV) 16 and/or HPV-18.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women aged 18 years and above

          -  Confirmed cervical infection with HPV types 16 and/or 18 at screening

          -  Cervical tissue specimen/slides provided to Study Pathology Adjudication Committee for
             diagnosis scheduled to be collected within 10 weeks prior to anticipated date of first
             dose of study drug

          -  Confirmed histologic evidence of cervical HSIL at screening

          -  Must be judged by Investigator to be an appropriate candidate for the
             protocol-specified procedure required at Week 36

          -  With respect to their reproductive capacity must be post-menopausal or surgically
             sterile or willing to use a contraceptive method with failure rate of less than 1% per
             year when used consistently and correctly from screening until Week 36

          -  Normal screening electrocardiogram (ECG)

        Exclusion Criteria:

          -  Microscopic or gross evidence of adenocarcinoma-in-situ (AIS), high grade vulvar,
             vaginal, or anal intraepithelial neoplasia or invasive cancer in any histopathologic
             specimen at screening

          -  Cervical lesion(s) that cannot be fully visualized on colposcopy

          -  History of endocervical curettage (ECC) which showed cervical HSIL indeterminate, or
             insufficient for diagnosis

          -  Treatment for cervical HSIL within 4 weeks prior to screening

          -  Pregnant, breastfeeding or considering becoming pregnant during the study

          -  History of previous therapeutic HPV vaccination

          -  Immunosuppression as a result of underlying illness or treatment

          -  Receipt of any non-study, non-live vaccine within 2 weeks of Day 0

          -  Receipt of any non-study, live vaccine within 4 weeks of Day 0

          -  Current or history of clinically significant, medically unstable disease or condition
             which, in the judgment of the investigator, would jeopardize the safety of the
             participant, interfere with study assessments or endpoint evaluation, or otherwise
             impact the validity of the study results

          -  Presence of acute or chronic bleeding or clotting disorder that would contraindicate
             IM injections, or use of blood thinners within 2 weeks of Day 0

          -  Participation in an interventional study with an investigational compound or device
             within 30 days of signing informed consent

          -  Less than two acceptable sites available for IM injection