Vulvar High Grade Squamous Intraepithelial Lesion (HSIL), Vulvar Dysplasia, Vulvar Intraepithelial Neoplasia (VIN), VIN2, VIN3, Pre-cancerous Lesions of the Vulva, Human Papillomavirus (HPV)
Conditions
Keywords
HPV-16, HPV-18
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
Interventions
BIOLOGICALVGX-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.
Participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.
DEVICECELLECTRA™ 2000
IM injection of VGX-3100 was followed by EP with the CELLECTRA™ 2000 device.
Sponsors
Inovio Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose | 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). |
| Percentage of Participants With Adverse Events (AEs) | 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. |
| Percentage of Participants With No Histologic Evidence of Vulvar HSIL | 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. |
| Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples | 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. |
| Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue | 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. |
| Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | 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. |
| Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer | 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. |
| Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s) | 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. |
| Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | 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. |
| Change From Baseline in Flow Cytometry Response Magnitude | 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. |
| Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 20 study sites in the United States from 31 August 2017 to 18 December 2020.
Pre-assignment details
A total of 70 participants were screened out of which 33 participants were enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| VGX-3100 + EP 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. | 25 |
| 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. | 8 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive Disease | 1 | 0 |
| Overall Study | Withdrawal by Subject (Not Related to AE) | 5 | 0 |
Baseline characteristics
| Characteristic | VGX-3100 + EP | VGX-3100 + EP + Imiquimod | Total |
|---|---|---|---|
| Age, Continuous | 50.2 years STANDARD_DEVIATION 12.86 | 45.4 years STANDARD_DEVIATION 9.13 | 49.1 years STANDARD_DEVIATION 12.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 8 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Other | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 21 Participants | 8 Participants | 29 Participants |
| Region of Enrollment United States | 25 participants | 8 participants | 33 participants |
| Sex: Female, Male Female | 25 Participants | 8 Participants | 33 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 8 |
| other Total, other adverse events | 23 / 25 | 8 / 8 |
| serious Total, serious adverse events | 3 / 25 | 0 / 8 |
Outcome results
Primary
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.
Time frame: Week 48
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples | 15.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples | 37.5 percentage of participants |
p-value: 0.0071Clopper Pearson
p-value: 0.0004Clopper Pearson
Secondary
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.
Time frame: Baseline; Week 27
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VGX-3100 + EP | Change From Baseline in Flow Cytometry Response Magnitude | Baseline | 0.150 SFU/10^6 PBMC |
| VGX-3100 + EP | Change From Baseline in Flow Cytometry Response Magnitude | Change from Baseline at Week 27 | 0.000 SFU/10^6 PBMC |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Flow Cytometry Response Magnitude | Baseline | 1.250 SFU/10^6 PBMC |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Flow Cytometry Response Magnitude | Change from Baseline at Week 27 | 0.000 SFU/10^6 PBMC |
Secondary
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.
Time frame: Baseline; Weeks 15, 27, 48, 74, and 96
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants available for analysis at individual time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 27) | 0.833 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 48) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 74) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 96) | 3.333 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Baseline) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 15) | 0.833 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 27) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 48) | 0.833 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 74) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 96) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Baseline) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 15) | 3.333 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 27) | 3.333 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 48) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 74) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 96) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Baseline) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 15) | 19.167 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 27) | 10.833 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 48) | 14.167 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 74) | 8.333 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 96) | 20.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Baseline) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 15) | 2.500 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Baseline) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 27) | 6.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 27) | 6.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 48) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 27) | 5.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 74) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 48) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 96) | 4.167 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 96) | 19.167 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Baseline) | 1.667 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 74) | 0.833 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 15) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 48) | 3.333 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 27) | 3.333 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 96) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 48) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E7 (Change From Baseline at Week 15) | 3.333 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 74) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Baseline) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E6 (Change From Baseline at Week 96) | 0.833 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 74) | 9.167 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Baseline) | 0.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-18 E6 (Change From Baseline at Week 15) | 10.000 spot forming units (SFU) per 10^6 cells |
| VGX-3100 + EP + Imiquimod | Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude | HPV-16 E7 (Change From Baseline at Week 15) | 1.667 spot forming units (SFU) per 10^6 cells |
Secondary
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.
Time frame: Weeks 15, 27, 48, 74, and 96
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis. 'Number analyzed' indicates the number of participants available for analysis at individual time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 48) | 15.9 reciprocal endpoint titer | Standard Deviation 3.33 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 15) | 24.8 reciprocal endpoint titer | Standard Deviation 3.73 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 27) | 44.7 reciprocal endpoint titer | Standard Deviation 3.67 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 27) | 9.6 reciprocal endpoint titer | Standard Deviation 3.24 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 48) | 69.3 reciprocal endpoint titer | Standard Deviation 3.87 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 74) | 14.5 reciprocal endpoint titer | Standard Deviation 3.31 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 74) | 83.2 reciprocal endpoint titer | Standard Deviation 3.98 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 15) | 7.3 reciprocal endpoint titer | Standard Deviation 3.22 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 96) | 2.9 reciprocal endpoint titer | Standard Deviation 1.86 |
| VGX-3100 + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 96) | 37.0 reciprocal endpoint titer | Standard Deviation 3.13 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 96) | 2.2 reciprocal endpoint titer | Standard Deviation 1.61 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 15) | 13.1 reciprocal endpoint titer | Standard Deviation 2.89 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 27) | 15.0 reciprocal endpoint titer | Standard Deviation 3.07 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 48) | 17.2 reciprocal endpoint titer | Standard Deviation 3.06 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 74) | 6.1 reciprocal endpoint titer | Standard Deviation 2.8 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-16 (Week 96) | 11.4 reciprocal endpoint titer | Standard Deviation 2.85 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 27) | 89.4 reciprocal endpoint titer | Standard Deviation 4.85 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 48) | 133.7 reciprocal endpoint titer | Standard Deviation 4.36 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 74) | 45.0 reciprocal endpoint titer | Standard Deviation 4.23 |
| VGX-3100 + EP + Imiquimod | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Anti-HPV-18 (Week 15) | 133.7 reciprocal endpoint titer | Standard Deviation 4.32 |
Secondary
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.
Time frame: From baseline up to Week 100
Population: Safety population included all participants who received at least 1 dose of VGX-3100 (with or without EP).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With Adverse Events (AEs) | 92.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With Adverse Events (AEs) | 100 percentage of participants |
Secondary
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).
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)
Population: Safety population included all participants who received at least one (1) dose of VGX-3100 (with or without EP).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose | 84.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose | 75.0 percentage of participants |
Secondary
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.
Time frame: Week 48
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples | 15.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples | 50.0 percentage of participants |
Secondary
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.
Time frame: Week 48
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology | 10.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology | 37.5 percentage of participants |
Secondary
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.
Time frame: Week 48
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With No Histologic Evidence of Vulvar HSIL | 15.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With No Histologic Evidence of Vulvar HSIL | 37.5 percentage of participants |
Secondary
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.
Time frame: Week 48
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue | 15.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue | 50.0 percentage of participants |
Secondary
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.
Time frame: From baseline up to Week 48
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + EP | Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer | 100.0 percentage of participants |
| VGX-3100 + EP + Imiquimod | Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer | 100.0 percentage of participants |
Secondary
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.
Time frame: From baseline to Week 48
Population: mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| VGX-3100 + EP | Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s) | 47.7 percent change in surface area | Standard Deviation 249.62 |
| VGX-3100 + EP + Imiquimod | Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s) | 10.5 percent change in surface area | Standard Deviation 117.95 |