Back to resultsEvaluation 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)
Primary Purpose
Vulvar High Grade Squamous Intraepithelial Lesion (HSIL), Vulvar Dysplasia, Vulvar Intraepithelial Neoplasia (VIN)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
VGX-3100
Imiquimod 5% Cream
CELLECTRA™ 2000
Sponsored by
About this trial
This is an interventional treatment trial for Vulvar High Grade Squamous Intraepithelial Lesion (HSIL) focused on measuring HPV-16, HPV-18
Eligibility 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.
Sites / Locations
- Christiana Care Health Systems
- Augusta University
- Rush University Medical Center
- Maine Medical Center
- University of Michigan
- St. Dominic Hospital
- Rutgers New Jersey
- Montefiore Medical Center
- Columbia University Medical Center
- Lyndhurst Clinical Research
- Complete HealthCare for Women, Inc.
- University of Pittsburgh Medical Center - Magee Womens Hospital
- Chattanooga's Program in Women's Oncology
- Vanderbilt University Medical Center
- Froedtert and The Medical College of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
VGX-3100 + EP
VGX-3100 + EP + Imiquimod
Arm Description
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.
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.
Outcomes
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
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.
Secondary Outcome Measures
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose
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).
Percentage of Participants With Adverse Events (AEs)
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.
Percentage of Participants With No Histologic Evidence of Vulvar HSIL
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.
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
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.
Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue
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.
Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology
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.
Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer
Non-progression of vulvar HSIL to vulvar cancer was evaluated from baseline to Week 48. Progression was defined as advancement to carcinoma by histology.
Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)
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.
Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude
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.
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.
Change From Baseline in Flow Cytometry Response Magnitude
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03180684
Brief Title
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)
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
August 31, 2017 (Actual)
Primary Completion Date
July 23, 2020 (Actual)
Study Completion Date
December 18, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Inovio Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. 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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vulvar High Grade Squamous Intraepithelial Lesion (HSIL), Vulvar Dysplasia, Vulvar Intraepithelial Neoplasia (VIN), VIN2, VIN3, Pre-cancerous Lesions of the Vulva, Human Papillomavirus (HPV)
Keywords
HPV-16, HPV-18
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VGX-3100 + EP
Arm Type
Experimental
Arm Description
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.
Arm Title
VGX-3100 + EP + Imiquimod
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
VGX-3100
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Imiquimod 5% Cream
Intervention Description
Participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.
Intervention Type
Device
Intervention Name(s)
CELLECTRA™ 2000
Intervention Description
IM injection of VGX-3100 was followed by EP with the CELLECTRA™ 2000 device.
Primary Outcome Measure Information:
Title
Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Description
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.
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose
Description
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).
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)
Title
Percentage of Participants With Adverse Events (AEs)
Description
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.
Time Frame
From baseline up to Week 100
Title
Percentage of Participants With No Histologic Evidence of Vulvar HSIL
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology
Description
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.
Time Frame
Week 48
Title
Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer
Description
Non-progression of vulvar HSIL to vulvar cancer was evaluated from baseline to Week 48. Progression was defined as advancement to carcinoma by histology.
Time Frame
From baseline up to Week 48
Title
Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)
Description
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.
Time Frame
From baseline to Week 48
Title
Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude
Description
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.
Time Frame
Baseline; Weeks 15, 27, 48, 74, and 96
Title
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
Description
A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.
Time Frame
Weeks 15, 27, 48, 74, and 96
Title
Change From Baseline in Flow Cytometry Response Magnitude
Description
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.
Time Frame
Baseline; Week 27
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Skolnik, MD
Organizational Affiliation
Inovio Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Christiana Care Health Systems
City
Newark
State/Province
Delaware
ZIP/Postal Code
19713
Country
United States
Facility Name
Augusta University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Maine Medical Center
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
St. Dominic Hospital
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
Rutgers New Jersey
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10461
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Lyndhurst Clinical Research
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Complete HealthCare for Women, Inc.
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43231
Country
United States
Facility Name
University of Pittsburgh Medical Center - Magee Womens Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Chattanooga's Program in Women's Oncology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37403
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232-2519
Country
United States
Facility Name
Froedtert and The Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
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)
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