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NCT03180684

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)

Completed Phase 2 Results posted Last updated 25 August 2023
What this trial tests

Phase 2 trial testing VGX-3100 in Vulvar High Grade Squamous Intraepithelial Lesion (HSIL) in 33 participants. Completed in 18 December 2020.

Timeline
31 August 2017
Primary endpoint
23 July 2020
18 December 2020

Quick facts

Lead sponsorInovio Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment33
Start date31 August 2017
Primary completion23 July 2020
Estimated completion18 December 2020
Sites15 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Inovio Pharmaceuticals — full company profile →

Who can join

18 and older, female only, with Vulvar High Grade Squamous Intraepithelial Lesion (HSIL) or Vulvar Dysplasia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples Primary · 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.

GroupValue95% CI
VGX-3100 + EP15.03.2 – 37.9
VGX-3100 + EP + Imiquimod37.58.5 – 75.5
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose Secondary · 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).

GroupValue95% CI
VGX-3100 + EP84.063.92 – 95.46
VGX-3100 + EP + Imiquimod75.034.91 – 96.81
Percentage of Participants With Adverse Events (AEs) Secondary · 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.

GroupValue95% CI
VGX-3100 + EP92.0
VGX-3100 + EP + Imiquimod100
Percentage of Participants With No Histologic Evidence of Vulvar HSIL Secondary · 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.

GroupValue95% CI
VGX-3100 + EP15.03.2 – 37.9
VGX-3100 + EP + Imiquimod37.58.5 – 75.5
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples Secondary · 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.

GroupValue95% CI
VGX-3100 + EP15.03.2 – 37.9
VGX-3100 + EP + Imiquimod50.015.7 – 84.3
Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue Secondary · 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.

GroupValue95% CI
VGX-3100 + EP15.03.2 – 37.9
VGX-3100 + EP + Imiquimod50.015.7 – 84.3
Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology Secondary · 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.

GroupValue95% CI
VGX-3100 + EP10.01.2 – 31.7
VGX-3100 + EP + Imiquimod37.58.5 – 75.5
Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer Secondary · 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.

GroupValue95% CI
VGX-3100 + EP100.083.2 – 100.0
VGX-3100 + EP + Imiquimod100.063.1 – 100.0
Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s) Secondary · 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.

GroupValue95% CI
VGX-3100 + EP47.7± 249.62
VGX-3100 + EP + Imiquimod10.5± 117.95
Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude Secondary · 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.

HPV-16 E6 (Baseline)
GroupValue95% CI
VGX-3100 + EP1.6670.00 – 35.00
VGX-3100 + EP + Imiquimod1.6670.00 – 8.33
HPV-16 E6 (Change From Baseline at Week 15)
GroupValue95% CI
VGX-3100 + EP0.8330.00 – 78.33
VGX-3100 + EP + Imiquimod0.0000.00 – 43.33
HPV-16 E6 (Change From Baseline at Week 27)
GroupValue95% CI
VGX-3100 + EP0.8330.00 – 58.33
VGX-3100 + EP + Imiquimod3.3330.00 – 36.67
HPV-16 E6 (Change From Baseline at Week 48)
GroupValue95% CI
VGX-3100 + EP0.8330.00 – 56.67
VGX-3100 + EP + Imiquimod0.0000.00 – 3.33
HPV-16 E6 (Change From Baseline at Week 74)
GroupValue95% CI
VGX-3100 + EP1.6670.00 – 30.00
VGX-3100 + EP + Imiquimod0.0000.00 – 25.00
HPV-16 E6 (Change From Baseline at Week 96)
GroupValue95% CI
VGX-3100 + EP1.6670.00 – 38.33
VGX-3100 + EP + Imiquimod0.8330.00 – 8.33
HPV-16 E7 (Baseline)
GroupValue95% CI
VGX-3100 + EP1.6670.00 – 15.00
VGX-3100 + EP + Imiquimod0.0000.00 – 1.67
HPV-16 E7 (Change From Baseline at Week 15)
GroupValue95% CI
VGX-3100 + EP3.3330.00 – 43.33
VGX-3100 + EP + Imiquimod1.6670.00 – 56.67
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Secondary · 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.

Anti-HPV-16 (Week 15)
GroupValue95% CI
VGX-3100 + EP7.3± 3.22
VGX-3100 + EP + Imiquimod13.1± 2.89
Anti-HPV-16 (Week 27)
GroupValue95% CI
VGX-3100 + EP9.6± 3.24
VGX-3100 + EP + Imiquimod15.0± 3.07
Anti-HPV-16 (Week 48)
GroupValue95% CI
VGX-3100 + EP15.9± 3.33
VGX-3100 + EP + Imiquimod17.2± 3.06
Anti-HPV-16 (Week 74)
GroupValue95% CI
VGX-3100 + EP14.5± 3.31
VGX-3100 + EP + Imiquimod6.1± 2.80
Anti-HPV-16 (Week 96)
GroupValue95% CI
VGX-3100 + EP37.0± 3.13
VGX-3100 + EP + Imiquimod11.4± 2.85
Anti-HPV-18 (Week 15)
GroupValue95% CI
VGX-3100 + EP24.8± 3.73
VGX-3100 + EP + Imiquimod133.7± 4.32
Anti-HPV-18 (Week 27)
GroupValue95% CI
VGX-3100 + EP44.7± 3.67
VGX-3100 + EP + Imiquimod89.4± 4.85
Anti-HPV-18 (Week 48)
GroupValue95% CI
VGX-3100 + EP69.3± 3.87
VGX-3100 + EP + Imiquimod133.7± 4.36
Change From Baseline in Flow Cytometry Response Magnitude Secondary · 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.

Baseline
GroupValue95% CI
VGX-3100 + EP0.1500.00 – 14.50
VGX-3100 + EP + Imiquimod1.2500.00 – 3.35
Change from Baseline at Week 27
GroupValue95% CI
VGX-3100 + EP0.0000.00 – 18.70
VGX-3100 + EP + Imiquimod0.0000.00 – 7.70

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first injection up to Week 100. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

VGX-3100 + EP
Serious: 3/25 (12%)
Deaths: 0/25
VGX-3100 + EP + Imiquimod
Serious: 0/8 (0%)
Deaths: 0/8

Serious adverse events (4 terms)

ReactionSystemVGX-3100 + EPVGX-3100 + EP + Imiquimod
Back painMusculoskeletal and connective tissue disorders
UlcerGeneral disorders
CellulitisInfections and infestations
Pulmonary massRespiratory, thoracic and mediastinal disorders
Other adverse events (64 terms — click to expand)

ReactionSystemVGX-3100 + EPVGX-3100 + EP + Imiquimod
Injection site painGeneral disorders
FatigueGeneral disorders
MyalgiaMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Injection site bruisingGeneral disorders
HeadacheNervous system disorders
Injection site swellingGeneral disorders
Injection site erythemaGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Injection site pruritisGeneral disorders
Vulvovaginal pruritisReproductive system and breast disorders
MalaiseGeneral disorders
DizzinessNervous system disorders
DiarrhoeaGastrointestinal disorders
Procedural painInjury, poisoning and procedural complications
Body temperature increasedInvestigations
Vulvovaginal discomfortReproductive system and breast disorders
Vulval disorderReproductive system and breast disorders
HypertensionVascular disorders
PalpitationsCardiac disorders
PyrexiaGeneral disorders
Influenza like illnessGeneral disorders
Urinary tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
HypoaesthesiaNervous system disorders
DepressionPsychiatric disorders
Urinary incontinenceRenal and urinary disorders
DyspareuniaReproductive system and breast disorders
Rhinitis allergicRespiratory, thoracic and mediastinal disorders
Sinus congestionRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
Hot flushVascular disorders
Ear painEar and labyrinth disorders
Vision blurredEye disorders
VomitingGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Application site painGeneral disorders
Injection site haemorrhageGeneral disorders

Most-reported serious reactions: Back pain, Ulcer, Cellulitis, Pulmonary mass.

Data from ClinicalTrials.gov NCT03180684 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Trial Watch: Toll-like receptor agonists in cancer immunotherapy.
    Smith M, García-Martínez E, Pitter MR, Fucikova J, et al · · 2018 · cited 171× · PMID 30524908 · DOI 10.1080/2162402x.2018.1526250
  2. Therapeutic Vaccines for HPV-Associated Malignancies.
    Smalley Rumfield C, Roller N, Pellom ST, Schlom J, et al · · 2020 · cited 87× · PMID 33117742 · DOI 10.2147/itt.s273327
  3. Application of toll-like receptors (TLRs) and their agonists in cancer vaccines and immunotherapy.
    Chakraborty S, Ye J, Wang H, Sun M, et al · · 2023 · cited 57× · PMID 37936697 · DOI 10.3389/fimmu.2023.1227833
  4. Therapeutic DNA Vaccines for Human Papillomavirus and Associated Diseases.
    Cheng MA, Farmer E, Huang C, Lin J, et al · · 2018 · cited 55× · PMID 29316817 · DOI 10.1089/hum.2017.197
  5. Pattern recognition receptors: function, regulation and therapeutic potential.
    Chen R, Zou J, Chen J, Zhong X, et al · · 2025 · cited 53× · PMID 40640149 · DOI 10.1038/s41392-025-02264-1
  6. Nucleic Acid-Based Approaches for Tumor Therapy.
    Hager S, Fittler FJ, Wagner E, Bros M. · · 2020 · cited 47× · PMID 32917034 · DOI 10.3390/cells9092061
  7. Toll-like receptor-targeted anti-tumor therapies: Advances and challenges.
    Yang Y, Li H, Fotopoulou C, Cunnea P, et al · · 2022 · cited 44× · PMID 36479129 · DOI 10.3389/fimmu.2022.1049340
  8. Current and future direction in treatment of HPV-related cervical disease.
    Khairkhah N, Bolhassani A, Najafipour R. · · 2022 · cited 44× · PMID 35478255 · DOI 10.1007/s00109-022-02199-y

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