Assessing Jet Administration of pBI-11 for the Treatment of Patients With HPV16/18+

This is a randomized phase II study. The primary goal of this study is to determine the safety and tolerability of three monthly pBI-11 DNA administrations in each thigh of patients with persistent human papillomavirus 16 (HPV16) and/or human papillomavirus (HPV18+).

This is a randomized phase II study. The primary goal of this study is two-fold; one is to determine the safety and tolerability of three monthly pBI-11 DNA administrations in each thigh of patients with persistent HPV16 and/or HPV18+ \< cervical intraepithelial neoplasia 2 (CIN2), wherein either 0.1 mL (0.3 mg) of the plasmid DNA is administered intradermally (I.D.) into each thigh (for a total of 0.6 mg DNA at each visit) using a Pharmajet Tropis device, or 0.5 mL (1.5 mg) of the plasmid DNA is administered intramuscularly (I.M.) into each thigh (for a total of 3 mg DNA at each visit) using a Pharmajet Stratis device; and the other is to evaluate the effect of vaccine on (HPV16/18) viral DNA clearance. Secondary goals are to seek preliminary evidence of prevention of disease progression and assess induction of an HPV16/18-specific immune response to select the appropriate regimen for a subsequent phase III clinical trial. Persistence is defined as positivity on two sequential tests. A total of 72 participants will be enrolled in 4 arms of the study in a 2:1:2:1 ratio (24 patients randomized to the intervention and 12 patient randomized to placebo via Tropis device, and 24 patients randomized to the intervention and 12 patient randomized to placebo via Stratis device).

Eligibility Criteria:
Inclusion Criteria:

1. Patients must have:

   Negative for Intraepithelial Lesions (NEIL), Atypical Squamous Cells of Undetermined Significance (ASC-US), or Low-grade Squamous Intraepithelial Lesion (LSIL) determined by cervical cytology

   AND

   HPV16 and/or 18+ by Roche Cobas 4800, Roche Linear Array HPV Genotyping test, or other FDA-approved HPV genotyping test (Co-infections with HPV types other than HPV16/18 are permissible).
2. Age ≥ 18 years
3. Baseline Eastern Cooperative Oncology Group performance status of 0, 1 at the time of treatment administration.
4. Patients must have adequate organ function at the time of enrollment as defined by the following parameters:

   * White blood cell count ≥ 3,000
   * Absolute lymphocyte number ≥ 500
   * Absolute neutrophil count ≥ 1,500
   * Platelets ≥ 90,000
   * Hemoglobulin ≥ 9
   * Total bilirubin \< 3 X the institutional limit of normal
   * Aspartate Aminotransferase (AST)/Alanine Aminotransferase(ALT) \< 3 X the institutional limit of normal
   * Creatinine \< 2.5 X the institutional limit of normal
5. Women of child-bearing potential must agree to use long acting contraception (e.g. tubal ligation, intrauterine devine or hormonal implant) or two forms of contraception (e.g. barrier method, oral contraceptives) prior to study entry and for 3 months after final vaccination.
6. Ability to understand and the willingness to sign a written informed consent document.
7. Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Histologic evidence of CIN2, cervical intraepithelial neoplasia 3 (CIN3), adenocarcinoma in situ or malignancy.
2. Patients with a diagnosis of immunosuppression or active systemic use of immunosuppressive medications such as steroids.
3. Patients who are receiving any other investigational agents within 28 days prior to the first dose.
4. Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
5. Patients with a history of systemic autoimmune disease such as multiple sclerosis or systemic lupus erythematosus (SLE), but exclusive of a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.
6. Patients who are pregnant or breast feeding or plan to become pregnant within five months of first study treatment.
7. Patient with active infection of, or receiving treatment for Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), or Hepatitis B Virus (HBV).
8. History of prior malignancy with disease free interval \<5 years; however, individuals with completely resected basal cell or squamous cell carcinoma of the skin within this interval may be enrolled.