A Study of VGX-3100 DNA Vaccine With Electroporation in Patients With Cervical Intraepithelial Neoplasia Grade 2/3 or 3

Study Overview
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Brief Summary
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This is randomized, placebo controlled study to determine safety and efficacy of VGX-3100 DNA Vaccine delivered by Electroporation to adult women with biopsy-proven HPV 16 or 18 associated Cervical intraepithelial neoplasia grade 2/3 or 3.

Official Title
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Phase II Placebo Controlled Study of VGX-3100, (HPV16 E6/E7, HPV18 E6/E7 DNA Vaccine) Delivered IM Followed by Electroporation With CELLECTRA-5P for the Treatment of Biopsy-proven CIN 2/3 or CIN 3 With Documented HPV 16 or 18.

Conditions
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Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Biological: VGX 3100
* Biological: Placebo
* Device: CELLECTRA™-5P


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female subjects age 18-55 years; Histologically confirmed HPV-16 or HPV-18-associated CIN 2/3 or CIN 3 from tissue collected less than 10 weeks prior to Vaccination/EP #1 with no evidence of invasive cancer in any specimen; Colposcopy is satisfactory based on visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area; lesions in ≤ 3 cervical quadrants (4 quadrant disease where the lesion occupies less than 50% of each quadrant will be considered for inclusion); Healthy subjects as judged by the Investigator based on medical history, PE, and normal results for an ECG, CBC, Serum Chemistries, CPK and urinalysis done up to 4 weeks prior to enrollment and administration of study drug; Women of child-bearing potential agree to remain sexually abstinent, use two medically effective methods of contraception (e.g. oral contraception, barrier methods, spermicide, intrauterine device (IUD)), or have a partner who is sterile (i.e., vasectomy) through 36 weeks (9 months); Able and willing to comply with all study procedures and voluntarily signs informed consent form Exclusion Criteria: Unsatisfactory colposcopy defined as incomplete visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area; Pregnancy or breastfeeding Immunosuppression including any concurrent condition requiring the continued use of systemic or topical steroids at or near the injection site [deltoid, upper arm] (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents. All other corticosteroids must be discontinued > 4 weeks prior to Day 0 of study vaccine administration; autoimmune disorders, transplant recipients; History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines (e.g. Gardasil®, Cervarix®) are not excluded); Positive serological test for hepatitis C virus or hepatitis B virus surface antigen(HBsAg) or human immunodeficiency virus (HIV) Administration of any blood product within 3 months of enrollment Administration of any licensed vaccine within 2 weeks of enrollment( 4weeks for measles vaccine) Participation in a study with an investigational compound or device within 30 days of signing informed consent; Cardiac pre-excitation syndromes (such as Wolff-Parkinson-White); History of seizures (unless seizure free for 5 years); Tattoos, scars, or active lesions/rashes within 2 cm of the intended site of vaccination/EP or any implantable leads; or any implantable leads; Active drug or alcohol use or dependence that, in the opinion of the investigator,would interfere with adherence to study requirements; Prisoners or subjects who are compulsorily detained (involuntarily incarcerated)for treatment of either a psychiatric or physical (i.e. infections disease) illness must not be enrolled into this study; Any other conditions judged by the investigator that would limit the evaluation of a subject

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VGX 3100<br> | Biological: VGX 3100<br>* 1ml of VGX-3100 delivered IM followed by electroporation at Day 0, Week 4 and Week 12.<br>Device: CELLECTRA™-5P<br>* CELLECTRA™-5P is used for electroporation following IM delivery of VGX 3100 or placebo on Day 0, Week 4 and Week 12.<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* 1ml of placebo delivered IM followed by electroporation at Day 0, Week 4 and Week 12.<br>Device: CELLECTRA™-5P<br>* CELLECTRA™-5P is used for electroporation following IM delivery of VGX 3100 or placebo on Day 0, Week 4 and Week 12.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Histopathological Regression of Cervical Lesions to CIN 1 or Less as a Measure of Efficacy. | The number of participants with histopathologically confirmed CIN2/3 or CIN 3 associated with HPV16 or HPV18 whose cervical lesions regress to CIN 1 or less at the 36 week visit. | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Virologically-proven Clearance of HPV 16 or 18 in Combination with Histopathological Regression of Cervical Lesions to CIN 1 or Less as a Secondary Measure of Efficacy | The number of participants with histopathologically confirmed CIN2/3 or CIN 3 associated with HPV16 or HPV18 whose cervical lesions regress to CIN 1 or less and have virologically-proven clearance of HPV16 or HPV18 at the 36 week visit. | 36 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CIN 2/3 or CIN 3, Cervical cancer, Papillomavirus