REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

A Prospective, Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of VGX-3100 Delivered Intramuscularly Followed by Electroporation With CELLECTRA™ 5PSP for the Treatment of HPV-16 and/or HPV-18 Related High Grade Squamous Intraepithelial Lesion (HSIL) of the Cervix

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03721978

Enrollment

203

Registered

2018-10-26

Start date

2019-02-28

Completion date

2022-09-15

Last updated

2024-10-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cervical Dysplasia, Cervical High Grade Squamous Intraepithelial Lesion, HSIL

Keywords

Cervical intraepithelial neoplasia (CIN), CIN 2, CIN 3, Human papillomavirus (HPV), HPV-16, HPV-18, High Grade Squamous Intraepithelial Lesion (HSIL), papillomavirus

Brief summary

HPV-303 is a prospective, randomized, double-blind, placebo-controlled study of VGX-3100 delivered intramuscularly (IM) followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed high-grade squamous intraepithelial lesions (HSIL) (cervical intraepithelial neoplasia grade 2 \[CIN2\] or grade 3 \[CIN3\]) of the cervix, associated with human papillomavirus (HPV-16) and/or HPV-18.

Interventions

BIOLOGICALVGX-3100

1 milliliter (mL) VGX-3100 injected IM.

BIOLOGICALMatched Placebo

1 mL of matched Placebo injected IM.

DEVICECELLECTRA™-5PSP

CELLECTRA™-5PSP used for EP following IM injection of VGX 3100.

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

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
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples	At Week 36	Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at Week 36, and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Secondary

Measure	Time frame	Description
Safety Population: Number of Participants With Local and Systemic AEs	From Baseline to Week 40	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 the pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as AEs. Nausea, chills, fatigue, injection site bruising, injection site erythema, injection site haematoma, injection site haemorrhage, injection site induration, injection site oedema, injection site pain, injection site paraesthesia, injection site pruritus, injection site swelling, malaise, pain, pyrexia, temperature regulation disorder, arthralgia, myalgia, headache and erythema were considered as local and systemic AEs for safety population.
Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	From Baseline to Week 40	AE is any untoward medical occurrence in a participant administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. Serious AE (SAE) is any experience that suggested significant hazard, contraindication, side effect/precaution, & fulfilled any of the following: fatal, life-threatening, required in-patient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant/required intervention to prevent other outcomes. TEAEs are any AEs starting on or after the first administration of any investigational product (IP). TEAEs included both serious and non-serious TEAEs. UADE is any SAE on health/safety or any life-threatening problem/death caused by, or associated with a device, if that effect, problem/death was not previously identified in nature, severity/degree of incidence in the investigational plan or application.
Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	From Baseline to Week 40	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. SAE is any experience that suggested significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal, 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 other outcomes. TEAEs are defined as AEs starting on or after the first administration of any IP. TEAEs included both serious and non-serious TEAEs. UADE is any SAE on health/safety or any life-threatening problem/death caused by, or associated with a device, if that effect, problem/death was not previously identified in nature, severity/degree of incidence in the investigational plan or application.
ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples	At 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 Week 36, and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample	At Week 36	Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample 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. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample	At Week 36	Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample 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. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing	At Week 36	Baseline biomarker-positive participants with no evidence of HPV-16 and/or HPV-18 at Week 36 time frame and participants in whom 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing	At Week 36	Participants with no evidence of HPV-16 and/or HPV-18 at Week 36 and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample	At Week 36	Baseline biomarker-positive participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample	At Week 36	Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing	At Week 36	Baseline biomarker-positive participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at Week 36, and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	From Baseline to Week 40	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 the pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as AEs. Nausea, fatigue, injection site bruising, injection site erythema, injection site haematoma, injection site induration, injection site pain, injection site pruritus, injection site swelling, malaise, pyrexia, arthralgia, myalgia, headache and erythema were considered as local and systemic AEs for baseline biomarker-positive participants for safety population.
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma	From Baseline at Week 36	Baseline biomarker-positive participants with no histologic evidence of cervical adenocarcinoma in situ (AIS) or cervical carcinoma at Week 36 relative to baseline and participants in whom an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered as responders. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma	From Baseline at Week 36	Participants with no histologic evidence of cervical AIS or cervical carcinoma at Week 36 relative to baseline and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.
Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations	From Baseline at Week 36	Percentage of baseline biomarker-positive participants who have cleared HPV-16 and/or HPV-18 on specimens from non-cervical anatomic locations (oropharynx, vagina and intra-anal) at Week 36 Visit compared to baseline were reported.
ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations	From Baseline at Week 36	Percentage of participants who have cleared HPV-16 and/or HPV-18 on specimens from non-cervical anatomic locations (oropharynx, vagina, and intra-anal) at Week 36 Visit compared to baseline were reported.
Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	At 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. E7 is a viral protein produced by cells infected by HPV-16/18.
mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	At Week 15 and Week 36	A standardized binding ELISA was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100. E7 is a viral protein produced by cells infected by HPV-16/18.
Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	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. E6 and E7 are viral proteins produced by cells infected by HPV-16/18.
mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	Baseline; Week 15 and Week 36	Assessment of cellular immune activity occurred via the application of the IFN-γ ELISpot. PBMCs isolated from whole blood sample were used for analysis. E6 and E7 are viral proteins produced by cells infected by HPV-16/18.
Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	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, changes from baseline in the percentage of CD8+CD137+Perforin+, CD8+CD38+Perforin+, and CD8+CD69+Perforin+ are reported.
mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	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, changes from baseline in the percentage of CD8+CD137+Perforin+, CD8+CD38+Perforin+, and CD8+CD69+Perforin+ are reported.
ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing	At Week 36	Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at Week 36, and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Countries

Argentina, Brazil, Estonia, Finland, Lithuania, Poland, Puerto Rico, South Africa, Spain, United States

Participant flow

Recruitment details

Participants took part in the study at 53 study sites from 28 February 2019 to 15 September 2022.

Pre-assignment details

A total of 203 participants with human papillomavirus (HPV)-16 and/or HPV-18 related high-grade squamous intraepithelial lesion (HSIL) of the cervix were randomized in 2:1 to receive either VGX-3100+Electroporation (EP) or Matched Placebo+EP.

Participants by arm

Arm	Count
VGX-3100 + EP Participants received 3 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.	134
Matched Placebo + EP Participants received 3 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.	69
Total	203

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	1
Overall Study	Lost to Follow-up	5	1
Overall Study	Progressive Disease	1	0
Overall Study	Reason not Specified	0	2
Overall Study	Withdrawal by Subject	6	1

Baseline characteristics

Characteristic	VGX-3100 + EP	Matched Placebo + EP	Total
Age, Continuous	31.6 years STANDARD_DEVIATION 6.98	31.1 years STANDARD_DEVIATION 7.93	31.4 years STANDARD_DEVIATION 7.3
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants	16 Participants	41 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	108 Participants	53 Participants	161 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Asian	3 Participants	0 Participants	3 Participants
Race/Ethnicity, Customized Black or African American	8 Participants	2 Participants	10 Participants
Race/Ethnicity, Customized Multiple	5 Participants	1 Participants	6 Participants
Race/Ethnicity, Customized Other	2 Participants	0 Participants	2 Participants
Race/Ethnicity, Customized White	116 Participants	66 Participants	182 Participants
Sex: Female, Male Female	134 Participants	69 Participants	203 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 134	0 / 67	0 / 1
other Total, other adverse events	131 / 134	67 / 67	1 / 1
serious Total, serious adverse events	9 / 134	9 / 67	0 / 1

Outcome results

Primary

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples

Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at Week 36, and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized. Only baseline biomarker-positive participants were planned to be analyzed for this outcome measure. Baseline Biomarker-positive Participants for ITT included participants from ITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples	28.6 percentage of participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples	0 percentage of participants

p-value: 0.11595% CI: [-24.6, 50.4]Miettinen and Nurminen method

Secondary

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations

Percentage of baseline biomarker-positive participants who have cleared HPV-16 and/or HPV-18 on specimens from non-cervical anatomic locations (oropharynx, vagina and intra-anal) at Week 36 Visit compared to baseline were reported.

Time frame: From Baseline at Week 36

Population: ITT population included all participants who were randomized. Only baseline biomarker-positive participants were planned to be analyzed for this outcome measure. Baseline Biomarker-positive Participants for ITT included participants from the ITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations	19.0 percentage of participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations	25.0 percentage of participants

95% CI: [-54.7, 25.8]

Secondary

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing

Baseline biomarker-positive participants with no evidence of HPV-16 and/or HPV-18 at Week 36 time frame and participants in whom 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized. Only baseline biomarker-positive participants were planned to be analyzed for this outcome measure. Baseline Biomarker-positive Participants for ITT included participants from the ITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing	38.1 percentage of participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing	0 percentage of participants

95% CI: [-15.7, 59.5]

Secondary

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing

Baseline biomarker-positive participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at Week 36, and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized. Only baseline biomarker-positive participants were planned to be analyzed for this outcome measure. Baseline Biomarker-positive Participants for ITT included participants from the ITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing	28.6 percentage of participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing	0 percentage of participants

95% CI: [-24.6, 50.4]

Secondary

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample

Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample 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. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized. Only baseline biomarker-positive participants were planned to be analyzed for this outcome measure. Baseline Biomarker-positive Participants for ITT included participants from the ITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample	38.1 percentage of participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample	25.0 percentage of participants

95% CI: [-37.7, 46]

Secondary

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample

Baseline biomarker-positive participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample	38.1 percentage of participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample	25.0 percentage of participants

95% CI: [-37.7, 46]

Secondary

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma

Baseline biomarker-positive participants with no histologic evidence of cervical adenocarcinoma in situ (AIS) or cervical carcinoma at Week 36 relative to baseline and participants in whom an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered as responders. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: From Baseline at Week 36

Population: ITT population included all participants who were randomized. Only baseline biomarker-positive participants were planned to be analyzed for this outcome measure. Baseline Biomarker-positive Participants for ITT included participants from the ITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma	76.2 percentage of participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma	75.0 percentage of participants

95% CI: [-31.2, 50.5]

Secondary

Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at 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, changes from baseline in the percentage of CD8+CD137+Perforin+, CD8+CD38+Perforin+, and CD8+CD69+Perforin+ are reported.

Time frame: Baseline, Week 15

Population: Baseline Biomarker-positive Participants for mITT=participants from the mITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood. Overall number of participants analyzed is the number of participants with data available for this outcome measure. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Arm	Measure	Group	Value (MEDIAN)
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Baseline	0.000 percentage of cells
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Change from Baseline at Week 15	0.035 percentage of cells
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Baseline	0.000 percentage of cells
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Change from Baseline at Week 15	0.005 percentage of cells
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Baseline	0.008 percentage of cells
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Change from Baseline at Week 15	0.042 percentage of cells
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Baseline	0.003 percentage of cells
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Baseline	0.020 percentage of cells
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Change from Baseline at Week 15	0.000 percentage of cells
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Change from Baseline at Week 15	0.002 percentage of cells
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Change from Baseline at Week 15	0.030 percentage of cells
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Baseline	0.027 percentage of cells

Comparison: Parameter: CD8+CD137+Perforin+95% CI: [-0.004, 0.325]

Comparison: Parameter: CD8+CD38+Perforin+95% CI: [0, 0.208]

Comparison: Parameter: CD8+CD69+Perforin+95% CI: [-0.055, 0.31]

Secondary

Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 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. E6 and E7 are viral proteins produced by cells infected by HPV-16/18.

Time frame: Baseline; Week 15 and Week 36

Population: mITT population=all participants who received at least one dose of study treatment and who had an analysis endpoint of interest. Baseline Biomarker-positive Participants for mITT=participants from mITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood. Overall number analyzed=number of participants with data available for this outcome measure. Number analyzed=number of participants with data available for analysis at the specified timepoints.

Arm	Measure	Group	Value (MEDIAN)
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Baseline	0.00 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Baseline	1.67 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 15	25.00 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 36	15.00 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 15	16.67 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 36	5.00 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Baseline	0.00 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 15	26.67 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 36	11.67 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Baseline	0.00 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 15	3.33 spot forming units (SFU)/10^6 PBMC
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 36	4.17 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 15	0.00 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Baseline	2.50 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Baseline	4.17 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Baseline	4.17 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 15	0.00 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 15	0.00 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 36	0.0 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Baseline	1.67 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 36	0.00 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 15	0.00 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 36	0.00 spot forming units (SFU)/10^6 PBMC
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 36	0.00 spot forming units (SFU)/10^6 PBMC

Comparison: HPV-16 E6: Week 1595% CI: [0, 73.33]

Comparison: HPV-16 E6: Week 3695% CI: [0, 38.33]

Comparison: HPV-16 E7: Week 1595% CI: [0, 85]

Comparison: HPV-16 E7: Week 3695% CI: [0, 36.67]

Comparison: HPV-18 E6: Week 1595% CI: [0, 181.67]

Comparison: HPV-18 E6: Week 3695% CI: [0, 31.67]

Comparison: HPV-18 E7: Week 1595% CI: [0, 46.67]

Comparison: HPV-18 E7: Week 3695% CI: [0, 20]

Secondary

Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody

A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100. E7 is a viral protein produced by cells infected by HPV-16/18.

Time frame: At Week 15 and Week 36

Population: mITT population included all participants who received at least one dose of study treatment and who had analysis endpoint of interest. Baseline Biomarker-positive Participants for mITT included participants from the mITT population who were biomarker-positive as identified by miRNA profiling performed from peripheral blood. Overall number of participants analyzed is the number of participants with data available for this outcome measure.

Arm	Measure	Group	Value (MEDIAN)
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 15	4050.0 reciprocal endpoint titer
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 36	13.0 reciprocal endpoint titer
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 36	675.0 reciprocal endpoint titer
VGX-3100 + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 15	450.0 reciprocal endpoint titer
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 36	1.0 reciprocal endpoint titer
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 36	1.0 reciprocal endpoint titer
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 15	1.0 reciprocal endpoint titer
Matched Placebo + EP	Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 15	1.0 reciprocal endpoint titer

Comparison: Week 15: HPV-16 E795% CI: [0, 18224]

Comparison: Week 36: HPV-16 E795% CI: [-18224, 674]

Comparison: Week 15: HPV-18 E795% CI: [224, 18224]

Comparison: Week 36: HPV-18 E795% CI: [-18000, 6074]

Secondary

Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)

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 the pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as AEs. Nausea, fatigue, injection site bruising, injection site erythema, injection site haematoma, injection site induration, injection site pain, injection site pruritus, injection site swelling, malaise, pyrexia, arthralgia, myalgia, headache and erythema were considered as local and systemic AEs for baseline biomarker-positive participants for safety population.

Time frame: From Baseline to Week 40

Population: Safety set included all participants who received at least one dose of study treatment. Only baseline biomarker-positive participants were planned to be analyzed for this outcome measure. Baseline Biomarker-positive Participants for the safety set included participants from the safety set who were biomarker-positive as identified by miRNA profiling performed from peripheral blood.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Haematoma	1 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Swelling	10 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Fatigue	10 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Malaise	2 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Induration	1 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Pyrexia	4 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Erythema	4 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Arthralgia	6 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Pain	19 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Myalgia	13 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Bruising	7 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Headache	13 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Pruritus	7 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Erythema	1 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Nausea	6 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Erythema	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Nausea	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Fatigue	2 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Bruising	1 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Erythema	2 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Haematoma	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Induration	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Pain	4 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Pruritus	2 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Injection Site Swelling	2 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Malaise	1 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Pyrexia	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Arthralgia	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Myalgia	2 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)	Headache	3 Participants

Secondary

Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])

AE is any untoward medical occurrence in a participant administered a pharmaceutical product, which does not necessarily have a causal relationship with the treatment. Serious AE (SAE) is any experience that suggested significant hazard, contraindication, side effect/precaution, & fulfilled any of the following: fatal, life-threatening, required in-patient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant/required intervention to prevent other outcomes. TEAEs are any AEs starting on or after the first administration of any investigational product (IP). TEAEs included both serious and non-serious TEAEs. UADE is any SAE on health/safety or any life-threatening problem/death caused by, or associated with a device, if that effect, problem/death was not previously identified in nature, severity/degree of incidence in the investigational plan or application.

Time frame: From Baseline to Week 40

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with any TEAEs	20 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with any Serious TEAEs	3 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with SUSAR	0 Participants
VGX-3100 + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with UADE	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with UADE	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with any TEAEs	4 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with SUSAR	0 Participants
Matched Placebo + EP	Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])	Participants with any Serious TEAEs	0 Participants

Secondary

ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations

Percentage of participants who have cleared HPV-16 and/or HPV-18 on specimens from non-cervical anatomic locations (oropharynx, vagina, and intra-anal) at Week 36 Visit compared to baseline were reported.

Time frame: From Baseline at Week 36

Population: ITT population included all participants who were randomized.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations	22.4 percentage of participants
Matched Placebo + EP	ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations	10.1 percentage of participants

95% CI: [1.1, 21.9]

Secondary

ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample

Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample	32.1 percentage of participants
Matched Placebo + EP	ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample	14.5 percentage of participants

95% CI: [5.2, 28.5]

Secondary

ITT Population: 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 Week 36 and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing	38.1 percentage of participants
Matched Placebo + EP	ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing	10.1 percentage of participants

95% CI: [16, 38.2]

Secondary

ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing

Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at Week 36, and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. No evidence of LSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing	26.1 percentage of participants
Matched Placebo + EP	ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing	5.8 percentage of participants

95% CI: [10.1, 29.5]

Secondary

ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample

Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants who did not have unscheduled excision or biopsy sample 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. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample	34.3 percentage of participants
Matched Placebo + EP	ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample	21.7 percentage of participants

95% CI: [-0.8, 24.5]

Secondary

ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample 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 Week 36, and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: At Week 36

Population: ITT population included all participants who were randomized.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples	27.6 percentage of participants
Matched Placebo + EP	ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples	8.7 percentage of participants

p-value: 0.00195% CI: [7.8, 28.6]Miettinen and Nurminen method

Secondary

ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma

Participants with no histologic evidence of cervical AIS or cervical carcinoma at Week 36 relative to baseline and participants who did not have unscheduled excision or biopsy sample obtained between the initial dose up to Week 36 were considered to be responders. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

Time frame: From Baseline at Week 36

Population: ITT population included all participants who were randomized.

Arm	Measure	Value (NUMBER)
VGX-3100 + EP	ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma	82.1 percentage of participants
Matched Placebo + EP	ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma	76.8 percentage of participants

95% CI: [-6, 17.9]

Secondary

mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15

Time frame: Baseline, Week 15

Population: mITT population included all participants who received at least one dose of clinical trial treatment and who had an analysis endpoint of interest. Overall number of participants analyzed is the number of participants with data available for this outcome measure. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Arm	Measure	Group	Value (MEDIAN)
VGX-3100 + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Baseline	0.001 percentage of cells
VGX-3100 + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Baseline	0.000 percentage of cells
VGX-3100 + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Change from Baseline at Week 15	0.049 percentage of cells
VGX-3100 + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Change from Baseline at Week 15	0.023 percentage of cells
VGX-3100 + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Baseline	0.003 percentage of cells
VGX-3100 + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Change from Baseline at Week 15	0.037 percentage of cells
Matched Placebo + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Baseline	0.007 percentage of cells
Matched Placebo + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Baseline	0.007 percentage of cells
Matched Placebo + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD38+Perforin+: Change from Baseline at Week 15	0.000 percentage of cells
Matched Placebo + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Baseline	0.012 percentage of cells
Matched Placebo + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD69+Perforin+: Change from Baseline at Week 15	0.000 percentage of cells
Matched Placebo + EP	mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15	CD8+CD137+Perforin+: Change from Baseline at Week 15	0.000 percentage of cells

Comparison: Parameter: CD8+CD137+Perforin+95% CI: [0.004, 0.077]

Comparison: Parameter: CD8+CD38+Perforin+95% CI: [0.003, 0.028]

Comparison: Parameter: CD8+CD69+Perforin+95% CI: [0.022, 0.053]

Secondary

mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36

Assessment of cellular immune activity occurred via the application of the IFN-γ ELISpot. PBMCs isolated from whole blood sample were used for analysis. E6 and E7 are viral proteins produced by cells infected by HPV-16/18.

Time frame: Baseline; Week 15 and Week 36

Arm	Measure	Group	Value (MEDIAN)
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 15	10.00 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Baseline	0.00 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Baseline	0.00 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 15	26.67 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 36	19.17 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Baseline	1.67 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Baseline	0.00 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 15	6.67 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 15	5.83 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 36	8.33 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 36	3.33 SFU/10^6 PBMC
VGX-3100 + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 36	3.33 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 36	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 15	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Baseline	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 15	1.67 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E6: Change from Baseline at Week 36	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Baseline	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 15	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-16 E7: Change from Baseline at Week 36	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Baseline	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E6: Change from Baseline at Week 36	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Baseline	0.00 SFU/10^6 PBMC
Matched Placebo + EP	mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36	HPV-18 E7: Change from Baseline at Week 15	0.00 SFU/10^6 PBMC

Comparison: HPV-16 E6: Week 1595% CI: [3.33, 11.67]

Comparison: HPV-16 E6: Week 3695% CI: [3.33, 11.67]

Comparison: HPV-16 E7: Week 1595% CI: [1.67, 11.67]

Comparison: HPV-16 E7: Week 3695% CI: [0, 5]

Comparison: HPV-18 E6: Week 1595% CI: [15, 40]

Comparison: HPV-18 E6: Week 3695% CI: [10, 28.33]

Comparison: HPV-18 E7: Week 1595% CI: [1.67, 6.67]

Comparison: HPV-18 E7: Week 3695% CI: [0, 3.33]

Secondary

mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody

A standardized binding ELISA was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100. E7 is a viral protein produced by cells infected by HPV-16/18.

Time frame: At Week 15 and Week 36

Population: mITT population included all participants who received at least one dose of study treatment and who had an analysis endpoint of interest. Overall number of participants analyzed is the number of participants with data available for this outcome measure. Number analyzed is the number of participants with data available for analysis at the specified timepoints.

Arm	Measure	Group	Value (MEDIAN)
VGX-3100 + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 15	225.0 reciprocal endpoint titer
VGX-3100 + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 36	1.0 reciprocal endpoint titer
VGX-3100 + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 15	2025.0 reciprocal endpoint titer
VGX-3100 + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 36	675.0 reciprocal endpoint titer
Matched Placebo + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 36	1.0 reciprocal endpoint titer
Matched Placebo + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 15	1.0 reciprocal endpoint titer
Matched Placebo + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-18 E7 at Week 15	1.0 reciprocal endpoint titer
Matched Placebo + EP	mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody	HPV-16 E7 at Week 36	1.0 reciprocal endpoint titer

Comparison: Week 15: HPV-16 E795% CI: [224, 674]

Comparison: Week 36: HPV-16 E795% CI: [0, 24]

Comparison: Week 15: HPV-18 E795% CI: [2024, 6074]

Comparison: Week 36: HPV-18 E795% CI: [224, 674]

Secondary

Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)

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. SAE is any experience that suggested significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal, 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 other outcomes. TEAEs are defined as AEs starting on or after the first administration of any IP. TEAEs included both serious and non-serious TEAEs. UADE is any SAE on health/safety or any life-threatening problem/death caused by, or associated with a device, if that effect, problem/death was not previously identified in nature, severity/degree of incidence in the investigational plan or application.

Time frame: From Baseline to Week 40

Population: Safety set included all participants who received at least one dose of study treatment. 1 participant received mixed treatment in error. Safety data for this participant has been presented in a separate arm.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
VGX-3100 + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with any TEAEs	131 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with any Serious TEAEs	9 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with SUSAR	0 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with UADE	0 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with UADE	0 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with any TEAEs	67 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with SUSAR	0 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with any Serious TEAEs	9 Participants
Mixed Treatment	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with UADE	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with any Serious TEAEs	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with SUSAR	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)	Participants with any TEAEs	1 Participants

Secondary

Safety Population: Number of Participants With Local and Systemic AEs

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 the pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as AEs. Nausea, chills, fatigue, injection site bruising, injection site erythema, injection site haematoma, injection site haemorrhage, injection site induration, injection site oedema, injection site pain, injection site paraesthesia, injection site pruritus, injection site swelling, malaise, pain, pyrexia, temperature regulation disorder, arthralgia, myalgia, headache and erythema were considered as local and systemic AEs for safety population.

Time frame: From Baseline to Week 40

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Haemorrhage	1 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Myalgia	56 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Arthralgia	29 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Nausea	36 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Erythema	1 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Haematoma	10 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Chills	2 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Pain	123 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Erythema	36 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Fatigue	56 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Swelling	43 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Bruising	21 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Headache	66 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Oedema	5 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Malaise	18 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Pruritus	33 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Pain	1 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Paraesthesia	1 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Induration	3 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Pyrexia	11 Participants
VGX-3100 + EP	Safety Population: Number of Participants With Local and Systemic AEs	Temperature Regulation Disorder	1 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Paraesthesia	0 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Arthralgia	14 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Temperature Regulation Disorder	0 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Pruritus	22 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Swelling	19 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Malaise	12 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Pain	1 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Pyrexia	5 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Myalgia	29 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Nausea	17 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Chills	1 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Fatigue	33 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Bruising	11 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Erythema	15 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Haematoma	7 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Haemorrhage	0 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Induration	0 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Oedema	2 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Pain	58 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Headache	37 Participants
Matched Placebo + EP	Safety Population: Number of Participants With Local and Systemic AEs	Erythema	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Arthralgia	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Malaise	1 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Haemorrhage	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Pain	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Erythema	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Induration	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Swelling	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Myalgia	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Oedema	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Pruritus	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Headache	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Pain	1 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Fatigue	1 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Pyrexia	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Bruising	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Chills	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Temperature Regulation Disorder	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Erythema	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Nausea	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Paraesthesia	0 Participants
Mixed Treatment	Safety Population: Number of Participants With Local and Systemic AEs	Injection Site Haematoma	0 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample

Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma

Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15

Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36

Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody

Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)

Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Treatment Emergent AEs (TEAEs) and Serious TEAEs (Including Suspected Unexpected Serious Adverse Reaction [SUSAR] and Unexpected Adverse Device Effect [UADE])

ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations

ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample

ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing

ITT Population: Percentage of Participants With No Evidence of LSIL or HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 by Type Specific HPV Testing

ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample

ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples

ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma

mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15

mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36

mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody

Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)

Safety Population: Number of Participants With Local and Systemic AEs