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
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)
Completion Date
Completion Date Type
Actual
Conditions
Vulvar High Grade Squamous Intraepithelial Lesion (HSIL)
Vulvar Dysplasia
Vulvar Intraepithelial Neoplasia (VIN)
VIN2
VIN3
Pre-cancerous Lesions of the Vulva
Human Papillomavirus (HPV)
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.
* 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.
Inclusion 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;
* 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;
Gender
Female
Gender Based
false
Keywords
HPV-16
HPV-18
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03180684
Org Class
Industry
Org Full Name
Inovio Pharmaceuticals
Org Study Id
HPV-201
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome 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.
Outcome Measure
Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Outcome Time Frame
Week 48
Secondary Outcomes
Outcome 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).
Outcome 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)
Outcome Measure
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose
Outcome 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.
Outcome Time Frame
From baseline up to Week 100
Outcome Measure
Percentage of Participants With Adverse Events (AEs)
Outcome 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.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants With No Histologic Evidence of Vulvar HSIL
Outcome 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.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Outcome 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.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue
Outcome 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.
Outcome Time Frame
Week 48
Outcome Measure
Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology
Outcome 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.
Outcome Time Frame
From baseline up to Week 48
Outcome Measure
Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer
Outcome 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.
Outcome Time Frame
From baseline to Week 48
Outcome Measure
Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)
Outcome 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.
Outcome Time Frame
Baseline; Weeks 15, 27, 48, 74, and 96
Outcome Measure
Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude
Outcome Description
A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.
Outcome Time Frame
Weeks 15, 27, 48, 74, and 96
Outcome Measure
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
Outcome 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.
Outcome Time Frame
Baseline; Week 27
Outcome Measure
Change From Baseline in Flow Cytometry Response Magnitude
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Anne Van Arsdale
Investigator Email
aarsdale@montefiore.org
Investigator Phone
718-904-2769
MeSH Terms
VGX-3100
IMIQUIMOD
AMINOQUINOLINES
QUINOLINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS