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)

• ClinicalTrials.gov Identifier: NCT03180684
• Recruitment Status: Completed
• First Posted: June 8, 2017
• Last Update Posted: September 5, 2021
• Sponsor: Inovio Pharmaceuticals
• Information provided by (Responsible Party): Inovio Pharmaceuticals

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 (Clinical Trial)
• 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: June 26, 2017
• Actual Primary Completion Date: July 23, 2020
• Actual Study Completion Date: December 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Safety: Percentage of Participants with Adverse Events [ Time Frame: From baseline to Week 100 ]
2. Percentage of Participants with No Histologic Evidence of Vulvar HSIL [ Time Frame: At Week 48 ]
3. Percentage of Participants with No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples [ Time Frame: At Week 48 ]
4. 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 [ Time Frame: At Week 48 ]
5. Percentage of Participants with No Progression of Vulvar HSIL to Vulvar Cancer [ Time Frame: From baseline to Week 48 ]
6. Percent Reduction from Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s) [ Time Frame: From baseline to Weeks 48, 74 and 96 ]
7. Change from Baseline in Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations [ Time Frame: From baseline to Weeks 15, 27, 48, 74 and 96 ]
8. Change from Baseline in Interferon-Gamma Response Magnitude [ Time Frame: From baseline to Weeks 15, 27, 48, 74 and 96 ]
9. Change from Baseline in Flow Cytometry Response Magnitude [ Time Frame: At baseline and Week 27 ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

United States, Delaware

Christiana Care Health Systems

Newark, Delaware, United States, 19713

United States, Georgia

Augusta University

Augusta, Georgia, United States, 30912

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Maine

Maine Medical Center

Scarborough, Maine, United States, 04074

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, Mississippi

St. Dominic Hospital

Jackson, Mississippi, United States, 39216

United States, New Jersey

Rutgers New Jersey

Newark, New Jersey, United States, 07103

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10461

Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

Lyndhurst Clinical Research

Winston-Salem, North Carolina, United States, 27103

United States, Ohio

Complete HealthCare for Women, Inc.

Columbus, Ohio, United States, 43231

United States, Pennsylvania

University of Pittsburgh Medical Center - Magee Womens Hospital

Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

Chattanooga's Program in Women's Oncology

Chattanooga, Tennessee, United States, 37403

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232-2519

United States, Wisconsin

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Sponsors and Collaborators

Inovio Pharmaceuticals

Investigators

• Study Director: Jeffrey Skolnik, MD; Inovio Pharmaceuticals

More Information

• Responsible Party: Inovio Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03180684
• Other Study ID Numbers: HPV-201
• First Posted: June 8, 2017
• Last Update Posted: September 5, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Inovio Pharmaceuticals:

HPV-16; HPV-18

Additional relevant MeSH terms:

Squamous Intraepithelial Lesions of the Cervix; Carcinoma, Squamous Cell; Carcinoma in Situ; Neoplasms; Uterine Cervical Dysplasia; Precancerous Conditions; Uterine Cervical Diseases; Uterine Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Squamous Cell; Imiquimod; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents; Interferon Inducers