REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

Study Overview
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Brief Summary
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HPV-303 is a prospective, randomized, double-blind, placebo-controlled phase 3 study of VGX-3100 delivered intramuscularly (IM) followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed high-grade squamous intraepithelial lesions (HSIL) (cervical intraepithelial neoplasia grade 2 [CIN2] or grade 3 [CIN3]) of the cervix, associated with HPV-16 and/or HPV-18.

Official Title
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Randomized Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL

Conditions
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Cervical Dysplasia, Cervical High Grade Squamous Intraepithelial Lesion, HSIL

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


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VGX-3100 + EP<br>IM injections with VGX-3100 followed by electroporation (EP) using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12. | Biological: VGX-3100<br>* 1 milliLiter (mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.<br>Device: CELLECTRA™-5PSP<br>* CELLECTRA™-5PSP is used for EP following IM injection of VGX 3100 or placebo on Day 0, Week 4 and Week 12.<br>|
| Placebo Comparator: Placebo + EP<br>IM injections with matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12. | Biological: Placebo<br>* 1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.<br>Device: CELLECTRA™-5PSP<br>* CELLECTRA™-5PSP is used for EP following IM injection 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 |
| --- | --- | --- |
| Percentage of Baseline Biomarker-Positive Women with No Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36 | Participants will be evaluated for evidence of cervical HSIL on histology as well as evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit. | At Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Number of Baseline Biomarker-Positive Women and all Women with Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment and for the Duration of the Study | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. | From baseline to Week 40 | 
| Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36 | Participants will be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit. | At Week 36 | 
| Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of Cervical HSIL on Histology Sample at Week 36 | Participants will be evaluated for evidence of cervical HSIL on histology at the Week 36 visit. | At Week 36 | 
| Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of Low Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36 | Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of cervical intraepithelial neoplasia grade 1 [CIN1], CIN2 or CIN3) on histology at the Week 36 visit. | At Week 36 | 
| Percentage of All Women with No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 at Week 36 | Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of CIN1, CIN2 or CIN3) on histology and be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit. | At Week 36 | 
| Percentage of Baseline Biomarker-Positive Women and All Women with No Progression of Cervical HSIL to Cervical Carcinoma from Baseline at Week 36 | Participants will be evaluated for progression of cervical HSIL to cervical carcinoma from baseline on histology at the Week 36 visit. | At Week 36 | 
| Percentage of Baseline Biomarker-Positive Women and All Women Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations at Week 36 | Participants will be evaluated for HPV-16 and/or HPV-18 status in specimens from non-cervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 Visit. | Baseline and Week 36 | 
| Among Baseline Biomarker-Positive Women and All Women Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations at Weeks 15 and 36 |  | At Weeks 15 and 36 | 
| Among Baseline Biomarker-Positive Women and All Women Interferon-gamma Response Magnitudes at Baseline, Weeks 15 and 36 | Interferon-gamma response magnitudes will be determined using the ELISpot assay at baseline, Weeks 15 and 36 visits. | At Baseline, Weeks 15 and 36 | 
| Among Baseline Biomarker-Positive Women and All Women Cellular Immune Response Magnitudes at Baseline and Week 15 | Using flow cytometry cellular immune response magnitudes will be determined at the baseline and Week 15 visits. | At Baseline and Week 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cervical intraepithelial neoplasia (CIN), CIN 2, CIN 3, Human papillomavirus (HPV), HPV-16, HPV-18, High Grade Squamous Intraepithelial Lesion (HSIL), papillomavirus