Cervical Dysplasia, Cervical High Grade Squamous Intraepithelial Lesion, HSIL
Conditions
Keywords
Cervical intraepithelial neoplasia (CIN), Human papillomavirus (HPV), High grade squamous intraepithelial lesion (HSIL), CIN 2, CIN 3, papillomavirus
Brief summary
HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular (IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 \[CIN2\] or grade 3 \[CIN3\]) associated with human papillomavirus (HPV) 16 and/or HPV-18.
Interventions
BIOLOGICALVGX-3100
1 mL VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.
BIOLOGICALPlacebo
1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.
DEVICEElectroporation (EP)
Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.
Sponsors
Inovio Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women aged 18 years and above * Confirmed cervical infection with HPV types 16 and/or 18 at screening * Cervical tissue specimen/slides provided to Study Pathology Adjudication Committee for diagnosis scheduled to be collected within 10 weeks prior to anticipated date of first dose of study drug * Confirmed histologic evidence of cervical HSIL at screening * Must be judged by Investigator to be an appropriate candidate for the protocol-specified procedure required at Week 36 * With respect to their reproductive capacity must be post-menopausal or surgically sterile or willing to use a contraceptive method with failure rate of less than 1% per year when used consistently and correctly from screening until Week 36 * Normal screening electrocardiogram (ECG)
Exclusion criteria
* Microscopic or gross evidence of adenocarcinoma-in-situ (AIS), high grade vulvar, vaginal, or anal intraepithelial neoplasia or invasive cancer in any histopathologic specimen at screening * Cervical lesion(s) that cannot be fully visualized on colposcopy * History of endocervical curettage (ECC) which showed cervical HSIL indeterminate, or insufficient for diagnosis * Treatment for cervical HSIL within 4 weeks prior to screening * Pregnant, breastfeeding or considering becoming pregnant during the study * History of previous therapeutic HPV vaccination * Immunosuppression as a result of underlying illness or treatment * Receipt of any non-study, non-live vaccine within 2 weeks of Day 0 * Receipt of any non-study, live vaccine within 4 weeks of Day 0 * Current or history of clinically significant, medically unstable disease or condition which, in the judgment of the investigator, would jeopardize the safety of the participant, interfere with study assessments or endpoint evaluation, or otherwise impact the validity of the study results * Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM injections, or use of blood thinners within 2 weeks of Day 0 * Participation in an interventional study with an investigational compound or device within 30 days of signing informed consent * Less than two acceptable sites available for IM injection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples | Week 36 | Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame, and participants in which excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With No Evidence of Cervical HSIL on Histology | Week 36 | Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. |
| Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing | Week 36 | Participants with no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®. |
| Percentage of Participants With No Evidence of LSIL or HSIL on Histology | Week 36 | Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment. |
| Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 | Week 36 | Participants with no histologic evidence of cervical HSIL, squamous atypia, and LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at the Week 36 time, and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. |
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study | From baseline up to Week 88 | An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. |
| Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations | Week 36 | Participants with no evidence of HPV-16 and/or HPV-18 on specimens from noncervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 time frame were considered as responder. |
| Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | Week 15 and Week 36 | 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 Interferon-Gamma Response Magnitude | Baseline; Week 15 and Week 36 | Assessment of cellular immune activity occurred via the application of the Interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISpot). Peripheral blood mononuclear cells (PBMCs) isolated from whole blood sample were used for analysis. |
| Change From Baseline in Flow Cytometry Response Magnitude | Baseline, Week 15 | Assessment of cellular immune activity was measured using the application flow cytometry for the purposes of performing a Lytic Granule Loading Assay. The Lytic Granule Loading assay examines the following external cellular markers: CD3, CD4, CD8 (T cell identification), CD137, CD38 and CD69 (T cell activation markers) as well as PD-1 (exhaustion/activation marker). Here change from baseline in CD8+CD137+Perforin+, CD8+CD38+Perforin+ and CD8+CD69+Perforin+ are reported. |
| Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma | Week 36 | Participants with no histologic evidence of cervical Adenocarcinoma in situ or cervical carcinoma at the Week 36 timeframe relative to baseline and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered as responders. |
Countries
Argentina, Belgium, Estonia, Finland, Germany, Italy, Lithuania, Mexico, Peru, Philippines, Poland, Portugal, Puerto Rico, Slovakia, South Africa, Spain, Thailand, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at 96 study centers in 20 countries from 28 June 2017 to 6 April 2021.
Pre-assignment details
A total of 201 participants with human papillomavirus (HPV)-16 and/or HPV-18 related high-grade squamous intraepithelial lesion (HSIL) of the cervix were randomized in this study, 138 in VGX-3100+EP and 63 in Placebo + EP.
Participants by arm
| Arm | Count |
|---|---|
| VGX-3100 + Electroporation (EP) Participants received three IM injections of 6 mg (in 1 mL) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | 138 |
| Placebo + EP Participants received three IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12. | 63 |
| Total | 201 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Progressive Disease | 1 | 0 |
| Overall Study | Protocol Deviation | 2 | 0 |
| Overall Study | Reason not Specified | 3 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 3 |
Baseline characteristics
| Characteristic | VGX-3100 + Electroporation (EP) | Total | Placebo + EP |
|---|---|---|---|
| Age, Continuous | 31.3 years STANDARD_DEVIATION 6.53 | 31.5 years STANDARD_DEVIATION 6.38 | 31.9 years STANDARD_DEVIATION 6.08 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 31 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 112 Participants | 166 Participants | 54 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 9 Participants | 15 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 8 Participants | 13 Participants | 5 Participants |
| Race/Ethnicity, Customized Missing | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 10 Participants | 12 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 109 Participants | 155 Participants | 46 Participants |
| Sex: Female, Male Female | 138 Participants | 201 Participants | 63 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 | 1 / 136 | 0 / 62 |
| other Total, other adverse events | 131 / 136 | 61 / 62 |
| serious Total, serious adverse events | 13 / 136 | 6 / 62 |
Outcome results
Primary
Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples
Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame, and participants in which excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®.
Time frame: Week 36
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + Electroporation (EP) | Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples | 22.5 percentage of participants |
| Placebo + EP | Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples | 11.1 percentage of participants |
p-value: 0.02995% CI: [-0.4, 21.2]Miettinen and Nurminen method
Secondary
Change From Baseline in Flow Cytometry Response Magnitude
Assessment of cellular immune activity was measured using the application flow cytometry for the purposes of performing a Lytic Granule Loading Assay. The Lytic Granule Loading assay examines the following external cellular markers: CD3, CD4, CD8 (T cell identification), CD137, CD38 and CD69 (T cell activation markers) as well as PD-1 (exhaustion/activation marker). Here change from baseline in CD8+CD137+Perforin+, CD8+CD38+Perforin+ and CD8+CD69+Perforin+ are reported.
Time frame: Baseline, Week 15
Population: mITT population included all participants who received at least one dose of clinical trial treatment and who had the analysis endpoint of interest. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VGX-3100 + Electroporation (EP) | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD137+Perforin+: Baseline | 0.004 SFU/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD137+Perforin+: Change from Baseline at Week 15 | 0.035 SFU/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD38+Perforin+: Baseline | 0.000 SFU/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD38+Perforin+: Change from Baseline at Week 15 | 0.011 SFU/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD69+Perforin+: Baseline | 0.009 SFU/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD69+Perforin+: Change from Baseline at Week 15 | 0.044 SFU/10^6 PBMC |
| Placebo + EP | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD69+Perforin+: Baseline | 0.001 SFU/10^6 PBMC |
| Placebo + EP | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD137+Perforin+: Baseline | 0.001 SFU/10^6 PBMC |
| Placebo + EP | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD38+Perforin+: Change from Baseline at Week 15 | 0.000 SFU/10^6 PBMC |
| Placebo + EP | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD137+Perforin+: Change from Baseline at Week 15 | 0.000 SFU/10^6 PBMC |
| Placebo + EP | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD69+Perforin+: Change from Baseline at Week 15 | 0.000 SFU/10^6 PBMC |
| Placebo + EP | Change From Baseline in Flow Cytometry Response Magnitude | CD8+CD38+Perforin+: Baseline | 0.000 SFU/10^6 PBMC |
Comparison: Parameter: CD8+CD137+Perforin+95% CI: [0.002, 0.046]
Comparison: Parameter: CD8+CD38+Perforin+95% CI: [0, 0.014]
Comparison: Parameter: CD8+CD69+Perforin+95% CI: [0.017, 0.058]
Secondary
Change From Baseline in Interferon-Gamma Response Magnitude
Assessment of cellular immune activity occurred via the application of the Interferon-γ enzyme-linked immunosorbent spot (IFN-γ ELISpot). Peripheral blood mononuclear cells (PBMCs) isolated from whole blood sample were used for analysis.
Time frame: Baseline; Week 15 and Week 36
Population: mITT population included all participants who received at least one dose of clinical trial treatment and who had the analysis endpoint of interest. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E6: Change from Baseline at Week 15 | 13.33 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E6: Baseline | 0.00 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E7: Baseline | 0.00 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E6: Change from Baseline at Week 15 | 50.83 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E6: Baseline | 0.83 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E6: Change from Baseline at Week 36 | 38.33 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E7: Baseline | 0.00 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E7: Change from Baseline at Week 15 | 10.83 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E7: Change from Baseline at Week 15 | 14.17 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E6: Change from Baseline at Week 36 | 8.33 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E7: Change from Baseline at Week 36 | 10.00 spot forming units (SFU)/10^6 PBMC |
| VGX-3100 + Electroporation (EP) | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E7: Change from Baseline at Week 36 | 7.50 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E7: Change from Baseline at Week 36 | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E6: Baseline | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E6: Change from Baseline at Week 15 | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E6: Change from Baseline at Week 36 | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E7: Baseline | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E7: Change from Baseline at Week 15 | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-16 E7: Change from Baseline at Week 36 | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E6: Baseline | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E6: Change from Baseline at Week 15 | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E7: Baseline | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E7: Change from Baseline at Week 15 | 0.00 spot forming units (SFU)/10^6 PBMC |
| Placebo + EP | Change From Baseline in Interferon-Gamma Response Magnitude | HPV-18 E6: Change from Baseline at Week 36 | 0.0 spot forming units (SFU)/10^6 PBMC |
Comparison: HPV-16 E6: Week 1595% CI: [8.33, 20]
Comparison: HPV-16 E6: Week 3695% CI: [3.33, 11.67]
Comparison: HPV-16 E7: Week 1595% CI: [5, 15]
Comparison: HPV-16 E7: Week 3695% CI: [1.67, 10]
Comparison: HPV-18 E6: Week 1595% CI: [31.67, 66.67]
Comparison: HPV-18 E6: Week 3695% CI: [18.33, 51.67]
Comparison: HPV-18 E7: Week 1595% CI: [6.67, 18.33]
Comparison: HPV-18 E7: Week 3695% CI: [5, 15]
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: Week 15 and Week 36
Population: mITT population included all participants who received at least one dose of clinical trial treatment and who had the analysis endpoint of interest. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| VGX-3100 + Electroporation (EP) | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-16 E7 at Week 15 | 225.0 reciprocal endpoint titer |
| VGX-3100 + Electroporation (EP) | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-16 E7 at Week 36 | 1.0 reciprocal endpoint titer |
| VGX-3100 + Electroporation (EP) | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-18 E7 at Week 15 | 2025.0 reciprocal endpoint titer |
| VGX-3100 + Electroporation (EP) | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-18 E7 at Week 36 | 225.0 reciprocal endpoint titer |
| Placebo + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-18 E7 at Week 36 | 1.0 reciprocal endpoint titer |
| Placebo + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-16 E7 at Week 15 | 1.0 reciprocal endpoint titer |
| Placebo + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-18 E7 at Week 15 | 1.0 reciprocal endpoint titer |
| Placebo + EP | Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations | HPV-16 E7 at Week 36 | 1.0 reciprocal endpoint titer |
Comparison: Week 15: HPV-16 E795% CI: [24, 224]
Comparison: Week 36: HPV-16 E795% CI: [0, 0]
Comparison: Week 15: HPV-18 E795% CI: [2000, 6050]
Comparison: Week 36: HPV-18 E795% CI: [74, 674]
Secondary
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.
Time frame: From baseline up to Week 88
Population: Safety set included all participants who received at least one dose of clinical trial treatment. One participant received mixed treatment and was excluded from the safety analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| VGX-3100 + Electroporation (EP) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study | Number of Participants with any AE | 131 Participants |
| VGX-3100 + Electroporation (EP) | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study | Number of Participants with any SAE | 13 Participants |
| Placebo + EP | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study | Number of Participants with any AE | 61 Participants |
| Placebo + EP | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study | Number of Participants with any SAE | 6 Participants |
Secondary
Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations
Participants with no evidence of HPV-16 and/or HPV-18 on specimens from noncervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 time frame were considered as responder.
Time frame: Week 36
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + Electroporation (EP) | Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations | 20.3 percentage of participants |
| Placebo + EP | Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations | 9.5 percentage of participants |
95% CI: [-0.5, 20.1]
Secondary
Percentage of Participants With No Evidence of Cervical HSIL on Histology
Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL.
Time frame: Week 36
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + Electroporation (EP) | Percentage of Participants With No Evidence of Cervical HSIL on Histology | 31.9 percentage of participants |
| Placebo + EP | Percentage of Participants With No Evidence of Cervical HSIL on Histology | 19.0 percentage of participants |
95% CI: [-0.6, 24.5]
Secondary
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing
Participants with no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®.
Time frame: Week 36
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + Electroporation (EP) | Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing | 34.1 percentage of participants |
| Placebo + EP | Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing | 15.9 percentage of participants |
95% CI: [5.1, 29.4]
Secondary
Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18
Participants with no histologic evidence of cervical HSIL, squamous atypia, and LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at the Week 36 time, and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment.
Time frame: Week 36
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + Electroporation (EP) | Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 | 18.1 percentage of participants |
| Placebo + EP | Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 | 6.3 percentage of participants |
95% CI: [1.5, 20.3]
Secondary
Percentage of Participants With No Evidence of LSIL or HSIL on Histology
Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment.
Time frame: Week 36
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + Electroporation (EP) | Percentage of Participants With No Evidence of LSIL or HSIL on Histology | 24.6 percentage of participants |
| Placebo + EP | Percentage of Participants With No Evidence of LSIL or HSIL on Histology | 11.1 percentage of participants |
95% CI: [1.7, 23.5]
Secondary
Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma
Participants with no histologic evidence of cervical Adenocarcinoma in situ or cervical carcinoma at the Week 36 timeframe relative to baseline and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered as responders.
Time frame: Week 36
Population: ITT population included all participants who were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| VGX-3100 + Electroporation (EP) | Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma | 84.1 percentage of participants |
| Placebo + EP | Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma | 85.7 percentage of participants |
95% CI: [-11.5, 10.3]