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)

August 23, 2023 updated by: Inovio Pharmaceuticals

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

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 high-grade squamous intraepithelial lesion (HSIL) [vulval intraepithelial neoplasia 2 or 3 (VIN 2 or VIN 3)] associated with human papilloma virus (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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

33

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Delaware
      • Newark, Delaware, United States, 19713
        • Christiana Care Health Systems
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Augusta University
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
    • Maine
      • Scarborough, Maine, United States, 04074
        • Maine Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan
    • Mississippi
      • Jackson, Mississippi, United States, 39216
        • St. Dominic Hospital
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Rutgers New Jersey
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center
      • New York, New York, United States, 10032
        • Columbia University Medical Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27103
        • Lyndhurst Clinical Research
    • Ohio
      • Columbus, Ohio, United States, 43231
        • Complete Healthcare for Women, Inc.
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center - Magee Womens Hospital
    • Tennessee
      • Chattanooga, Tennessee, United States, 37403
        • Chattanooga's Program in Women's Oncology
      • Nashville, Tennessee, United States, 37232-2519
        • Vanderbilt University Medical Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert and The Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VGX-3100 + EP
Participants with histologically confirmed vulvar high-grade squamous intraepithelial lesion (HSIL) associated with human papilloma virus (HPV) 16 and/or 18, received four doses of 6 mg VGX-3100 as an intramuscular (IM) injection on Day 0, Week 4, Week 12, and Week 24 followed by electroporation (EP) using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
Biological: VGX-3100
One milliliter (1 mL) VGX-3100 injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24.
Device: CELLECTRA™ 2000
IM injection of VGX-3100 was followed by EP with the CELLECTRA™ 2000 device.
Experimental: VGX-3100 + EP + Imiquimod
Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.
Biological: VGX-3100
One milliliter (1 mL) VGX-3100 injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24.
Device: CELLECTRA™ 2000
IM injection of VGX-3100 was followed by EP with the CELLECTRA™ 2000 device.
Drug: Imiquimod 5% Cream
Participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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: Week 48
A treatment responder for the primary endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or vulvar low grade squamous intraepithelial lesions (LSIL) [vulval intraepithelial neoplasia 1 (VIN1)] or condyloma) and no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.
Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose
Time Frame: 7 days following each dose: Day 0 (Days 0 to 7), Week 4 (Days 22 to 28), Week 12 (Days 78 to 84), Week 24 (Days 162 to 168), and Week 52 (Days 358 to 364)
An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. A TEAE was defined per protocol as any AE with onset after the administration of study medication through the end of the study (i.e., study discharge).
7 days following each dose: Day 0 (Days 0 to 7), Week 4 (Days 22 to 28), Week 12 (Days 78 to 84), Week 24 (Days 162 to 168), and Week 52 (Days 358 to 364)
Percentage of Participants With Adverse Events (AEs)
Time Frame: From baseline up to Week 100
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product.
From baseline up to Week 100
Percentage of Participants With No Histologic Evidence of Vulvar HSIL
Time Frame: Week 48
Participants with no histologic evidence of vulvar HSIL (normal tissue or vulvar LSIL [VIN1] or condyloma) based on histology (i.e. biopsies or excisional treatment) were considered. All lesions were evaluated for histologic evidence of vulvar HSIL.
Week 48
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Time Frame: Week 48
Participants with no evidence of HPV-16 and/or HPV-18 indicated the clearance of the specific HPV genotypes [16, 18, or both]. All lesions were evaluated for evidence of HPV-16/18 in vulvar tissue.
Week 48
Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue
Time Frame: Week 48
A treatment responder for the endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or LSIL [VIN1] or condyloma) based on histology (i.e. biopsies or excisional treatment) or no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.
Week 48
Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology
Time Frame: Week 48
Histologic regression was defined as a participant with no histologic evidence of vulvar HSIL, no evidence of LSIL (VIN1), and no evidence of condyloma. Histologic regression of vulvar HSIL to normal tissue was assessed.
Week 48
Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer
Time Frame: From baseline up to Week 48
Non-progression of vulvar HSIL to vulvar cancer was evaluated from baseline to Week 48. Progression was defined as advancement to carcinoma by histology.
From baseline up to Week 48
Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)
Time Frame: From baseline to Week 48
Lesion(s), defined as areas that stain acetowhite were assessed. Analysis of qualifying lesions was defined as the change in total surface area of only lesions with both baseline and Week 48 measurements. Percent change in the cumulative surface area of the acetowhite vulvar lesion(s) was determined by the quantitative analysis of standardized prebiopsy photographic imaging of qualifying lesion(s) at Week 48 compared to baseline.
From baseline to Week 48
Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude
Time Frame: Baseline; Weeks 15, 27, 48, 74, and 96
Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples. Assessment of cellular immune activity was performed by IFN-γ enzyme-linked immunosorbent spot-forming (ELISpot) assay.
Baseline; Weeks 15, 27, 48, 74, and 96
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
Time Frame: Weeks 15, 27, 48, 74, and 96
A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.
Weeks 15, 27, 48, 74, and 96
Change From Baseline in Flow Cytometry Response Magnitude
Time Frame: Baseline; Week 27
Assessment of cellular immune activity was measured using the application of flow cytometry for the purpose of performing a Lytic Granule Loading Assay. The Lytic Granule Loading Assay examines the following external cellular markers: cluster of differentiation 3 (CD3), CD4, CD8 (T-cell identification), CD137, CD38, and CD69 (T-cell activation markers) as well as PD-1 (exhaustion/activation marker). Here, a change from baseline in CD8+/CD137+ PBMCs expressing Perforin+ was reported.
Baseline; Week 27

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Inovio Pharmaceuticals

Investigators

  • Study Director: Jeffrey Skolnik, MD, Inovio Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 31, 2017

Primary Completion (Actual)

July 23, 2020

Study Completion (Actual)

December 18, 2020

Study Registration Dates

First Submitted

June 6, 2017

First Submitted That Met QC Criteria

June 6, 2017

First Posted (Actual)

June 8, 2017

Study Record Updates

Last Update Posted (Actual)

August 25, 2023

Last Update Submitted That Met QC Criteria

August 23, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HPV-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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