PVX4 for the Treatment of Human Papilloma Virus (HPV)16+ Cervical Dysplasia

PVX4 for the Treatment of Human Papilloma Virus (HPV)16+ Cervical Dysplasia

The purpose of this Phase 2 study is to compare the effects of administering the PVX4 combination device biologic product (pBI-4 DNA vaccine via electroporation-mediated intramuscular delivery with the TriGrid™ Delivery System) in patients with biopsy-confirmed, human papilloma virus (HPV) 16-associated high grade cervical intraepithelial neoplasia (CIN2/3) as compared to the administration of placebo.

Inclusion Criteria:

1. Female subjects 18-60 years old with biopsy-confirmed high grade cervical intraepithelial neoplasia (CIN2/3) confirmed by central review.
2. Patients whose cytobrush samples are HPV16+ by Roche Cobas genotyping test. Co-infections with HPV types other than HPV16 are permissible for study entry
3. HIV negative
4. Patients who are able and willing to comply with all study procedures, and with anticipated availability for the planned follow-up period of one year
5. Patients who are of childbearing potential agree to remain sexually abstinent, use methods of contraception (e.g. oral contraception, barrier methods, spermicide, intrauterine device (IUD)), or have a partner who is sterile (i.e., vasectomy) through 6 months.
6. Patients must have adequate organ function at the time of enrollment as defined by the following parameters: white blood cell count >3,000/mcL; lymphocyte number >500/mcL; absolute neutrophil count >1,000/mcL; platelets >90,000/mcL; hemoglobin >9 g/dL; total bilirubin <3 X the institutional limit of normal; aspartate aminotransferase (AST [SGOT]) / alanine aminotransferase (ALT [SGPT]) <3 X the institutional limit of normal; creatinine <2.5X the institutional limit of normal.

Exclusion Criteria:

1. Patients who are attempting pregnancy within 6 months, pregnant, or breastfeeding.

2. Patients with immunodeficiency, or treatment with immunosuppressive medications

3. Administration of any blood product within 3 months of enrollment.

4. Administration of any licensed vaccine within 2 weeks of enrollment (4 weeks for a live vaccine)

5. Participation in a study with an investigational compound or device within 30 days of signing informed consent.

6. History of seizures (unless seizure free for 5 years)

7. Previous cancer history within the past 5 years, except localized skin cancer.

8. Patients who have had chemotherapy, radiation, biological cancer therapy, or other investigational agents within 28 days prior to the first dose of study drug.

9. Patients who have had surgery within 28 days, excluding minor procedures (dental work, skin biopsy, etc).

10. 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.

11. Patients who have an active autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis).

12. Previous cervical conization or LEEP procedure or previous total hysterectomy due to cervical lesions at enrollment

13. High-grade intraepithelial lesions (CIN2/3) encompassing more than 180-degree (more than 2 quarters) of cervix

14. Positive HBV PCR if Hepatitis B surface antigen positive

15. Positive HCV PCR if anti-HCV positive

16. Border of high-grade intraepithelial lesions (CIN2/3) could not be completely observed by colposcope and positive for high grade disease by endocervical curettage.

17. Cervical biopsy and/or ECC of adenocarcinoma in situ (AIS)

18. Pre-biopsy Pap of Atypical Glandular Cells (AGC)/AGC favor neoplasm, squamous cell carcinoma (SCC), or cervical biopsy of CIN2/3 with postmenopausal bleeding

19. Participant has:

    1. Less than 2 acceptable potential injection sites for IM injection and electroporation considering the left and right medial deltoid, and anterolateral quadriceps muscles. A site for injection and electroporation is not acceptable if there is inadequate muscle mass to support at least a 19 mm/0.75 inch injection depth or a skinfold thickness measurement of ≥50 mm as assessed using the provided caliper. Eligible injection sites must also be free from tattoos, hypertrophic skin patches, keloids or other skin conditions which could interfere with the administration procedure or subsequent assessment of local reactogenicity.
    2. Note: To ensure adequate muscle mass for administrations, for participants with a weight ≤65 kg, potentially eligible administration sites are confined to the outer aspect of the upper thigh (left or right vastus lateralis muscle) (i.e., the left and right medial deltoid are not eligible administration sites).

20. Contraindication to intramsucular injections and blood draws.

21. A metal implant or implantable device within the area of the electroporation injection site at > 2 of the eligible injection sites.

22. A nonremovable electronic stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac defibrillator, nerve stimulators, or deep brain stimulators.

23. Participant is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.

24. Vulnerable participants (e.g., incarcerated individuals, individuals under a legal protection measure).