Evaluation of VGX-3100 and Electroporation Alone or in Combination With Imiquimod for the Treatment of HPV-16 and/or HPV-18 Related Vulvar HSIL (Also Referred as: VIN 2 or VIN 3)

Sponsor

Inovio Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03180684

Collaborator

(none)

Enrollment

Locations

Arms

41.8

Actual Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to test the safety and efficacy of an investigational immunotherapy VGX-3100, in combination with a study device, to treat women with vulvar HSIL (VIN 2 or VIN 3) associated with HPV types 16 and/or 18. VGX-3100 is being assessed as an alternative to surgery with the potential to clear the underlying HPV infection. For more information visit our study website at: www.VINresearchstudy.com

Condition or Disease	Intervention/Treatment	Phase
Vulvar High Grade Squamous Intraepithelial Lesion (HSIL) Vulvar Dysplasia Vulvar Intraepithelial Neoplasia (VIN) VIN2 VIN3 Pre-cancerous Lesions of the Vulva Human Papillomavirus (HPV)	Biological: VGX-3100 Drug: Imiquimod 5% cream Device: CELLECTRA™ 2000	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

33 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2, Randomized, Open Label, Efficacy Study of VGX-3100 Delivered Intramuscularly Followed by Electroporation With CELLECTRA™ 2000 Alone or in Combination With Imiquimod, for the Treatment of HPV-16 and/or HPV-18 Related High Grade Squamous Intraepithelial Lesion (HSIL) of the Vulva

Actual Study Start Date :

Jun 26, 2017

Actual Primary Completion Date :

Jul 23, 2020

Actual Study Completion Date :

Dec 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VGX-3100 + EP Intramuscular (IM) injections with VGX-3100 followed by EP using the CELLECTRA™ 2000 device on Day 0, Week 4, Week 12 and Week 24.	Biological: VGX-3100 One milliliter (1 mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24. A fifth dose and sixth dose of six mg VGX-3100 may be administered IM with EP per the judgment of the Investigator. Device: CELLECTRA™ 2000 IM injection of VGX-3100 is followed by EP with the CELLECTRA™ 2000 device.
Experimental: VGX-3100 + EP + Imiquimod IM injections with VGX-3100 followed by EP using the CELLECTRA™ 2000 device on Day 0, Week 4, Week 12 and Week 24. In addition, participants will apply imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.	Biological: VGX-3100 One milliliter (1 mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24. A fifth dose and sixth dose of six mg VGX-3100 may be administered IM with EP per the judgment of the Investigator. Drug: Imiquimod 5% cream Participants will apply imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks. Device: CELLECTRA™ 2000 IM injection of VGX-3100 is followed by EP with the CELLECTRA™ 2000 device.

Arm

Intervention/Treatment

Experimental: VGX-3100 + EP

Intramuscular (IM) injections with VGX-3100 followed by EP using the CELLECTRA™ 2000 device on Day 0, Week 4, Week 12 and Week 24.

Biological: VGX-3100

One milliliter (1 mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24. A fifth dose and sixth dose of six mg VGX-3100 may be administered IM with EP per the judgment of the Investigator.

Device: CELLECTRA™ 2000

IM injection of VGX-3100 is followed by EP with the CELLECTRA™ 2000 device.

Experimental: VGX-3100 + EP + Imiquimod

IM injections with VGX-3100 followed by EP using the CELLECTRA™ 2000 device on Day 0, Week 4, Week 12 and Week 24. In addition, participants will apply imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Biological: VGX-3100

Drug: Imiquimod 5% cream

Participants will apply imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Device: CELLECTRA™ 2000

IM injection of VGX-3100 is followed by EP with the CELLECTRA™ 2000 device.

Outcome Measures

Primary Outcome Measures

Percentage of Participants with No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples [At Week 48]

Secondary Outcome Measures

Safety: Percentage of Participants with Adverse Events [From baseline to Week 100]
Percentage of Participants with No Histologic Evidence of Vulvar HSIL [At Week 48]
Percentage of Participants with No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples [At Week 48]
Percentage of Participants with No Evidence of Vulvar HSIL, No Evidence of Vulvar Low Grade Squamous Intraepithelial Lesions (LSIL) (Vulvar Intraepithelial Neoplasia 1 [VIN1]), and No Evidence of Condyloma on Histology [At Week 48]
Percentage of Participants with No Progression of Vulvar HSIL to Vulvar Cancer [From baseline to Week 48]
Percent Reduction from Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s) [From baseline to Weeks 48, 74 and 96]
Change from Baseline in Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations [From baseline to Weeks 15, 27, 48, 74 and 96]
Change from Baseline in Interferon-Gamma Response Magnitude [From baseline to Weeks 15, 27, 48, 74 and 96]
Change from Baseline in Flow Cytometry Response Magnitude [At baseline and Week 27]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women aged 18 and above;
Have high grade squamous intraepithelial lesion (HSIL) of the vulva (VIN2 or VIN3) caused by infection with HPV types 16 and/or 18 confirmed at screening visit;

Exclusion Criteria:

Biopsy-proven differentiated VIN;
Any previous treatment for vulvar HSIL within 4 weeks prior to screening;
Allergy to imiquimod 5% cream or to an inactive ingredient in imiquimod 5% cream;
Pregnant, breastfeeding or considering becoming pregnant within 6 months following the last dose of investigational product;
Immunosuppression as a result of underlying illness or treatment;
Significant acute or chronic medical illness.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Christiana Care Health Systems	Newark	Delaware	United States	19713
2	Augusta University	Augusta	Georgia	United States	30912
3	Rush University Medical Center	Chicago	Illinois	United States	60612
4	Maine Medical Center	Scarborough	Maine	United States	04074
5	University of Michigan	Ann Arbor	Michigan	United States	48109
6	St. Dominic Hospital	Jackson	Mississippi	United States	39216
7	Rutgers New Jersey	Newark	New Jersey	United States	07103
8	Montefiore Medical Center	Bronx	New York	United States	10461
9	Columbia University Medical Center	New York	New York	United States	10032
10	Lyndhurst Clinical Research	Winston-Salem	North Carolina	United States	27103
11	Complete HealthCare for Women, Inc.	Columbus	Ohio	United States	43231
12	University of Pittsburgh Medical Center - Magee Womens Hospital	Pittsburgh	Pennsylvania	United States	15213
13	Chattanooga's Program in Women's Oncology	Chattanooga	Tennessee	United States	37403
14	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-2519
15	Froedtert and The Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226