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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Inovio Pharmaceuticals
- Enrollment
- 33
- Locations
- 15
- Primary Endpoint
- Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts 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.
Arms & Interventions
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.
Intervention: VGX-3100 (Biological)
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.
Intervention: CELLECTRA™ 2000 (Device)
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.
Intervention: VGX-3100 (Biological)
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.
Intervention: Imiquimod 5% Cream (Drug)
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.
Intervention: CELLECTRA™ 2000 (Device)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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))
- Percentage of Participants With Adverse Events (AEs)(From baseline up to Week 100)
- Percentage of Participants With No Histologic Evidence of Vulvar HSIL(Week 48)
- Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples(Week 48)
- Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No 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(Week 48)
- Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer(From baseline up to Week 48)
- Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)(From baseline to Week 48)
- Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude(Baseline; Weeks 15, 27, 48, 74, and 96)
- Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations(Weeks 15, 27, 48, 74, and 96)
- Change From Baseline in Flow Cytometry Response Magnitude(Baseline; Week 27)