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)
- Conditions
- Vulvar High Grade Squamous Intraepithelial Lesion (HSIL)Vulvar DysplasiaVulvar Intraepithelial Neoplasia (VIN)VIN2VIN3Pre-cancerous Lesions of the VulvaHuman Papillomavirus (HPV)
- Interventions
- Registration Number
- NCT03180684
- Lead Sponsor
- Inovio Pharmaceuticals
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 33
- 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;
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description VGX-3100 + EP VGX-3100 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. VGX-3100 + EP CELLECTRA™ 2000 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. VGX-3100 + EP + Imiquimod VGX-3100 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. VGX-3100 + EP + Imiquimod Imiquimod 5% Cream 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. VGX-3100 + EP + Imiquimod CELLECTRA™ 2000 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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.
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.
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.
Trial Locations
- Locations (15)
St. Dominic Hospital
🇺🇸Jackson, Mississippi, United States
Complete HealthCare for Women, Inc.
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center - Magee Womens Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Christiana Care Health Systems
🇺🇸Newark, Delaware, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Augusta University
🇺🇸Augusta, Georgia, United States
Maine Medical Center
🇺🇸Scarborough, Maine, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Chattanooga's Program in Women's Oncology
🇺🇸Chattanooga, Tennessee, United States
Rutgers New Jersey
🇺🇸Newark, New Jersey, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Lyndhurst Clinical Research
🇺🇸Winston-Salem, North Carolina, United States
Froedtert and The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States