Evaluation of VGX-3100 and Electroporation Alone or in Co... | NCT03180684

Label	Type	Description	Intervention Names
VGX-3100 + EP	Experimental	Participants with histologically confirmed vulvar high-grade squamous intraepithelial lesion (HSIL) associated with human papilloma virus (HPV) 16 and/or 18, received four doses of 6 mg VGX-3100 as an intramuscular (IM) injection on Day 0, Week 4, Week 12, and Week 24 followed by electroporation (EP) using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.	Biological: VGX-3100 Device: CELLECTRA™ 2000
VGX-3100 + EP + Imiquimod	Experimental	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.	Biological: VGX-3100 Drug: Imiquimod 5% Cream Device: CELLECTRA™ 2000

Name	Type	Description	Arm Group Labels	Other Names
VGX-3100	Biological	One milliliter (1 mL) VGX-3100 injected IM and delivered by EP using CELLECTRA™ 2000 on Day 0, Week 4, Week 12 and Week 24.	VGX-3100 + EP VGX-3100 + EP + Imiquimod

Measure	Description	Time Frame
Percentage of Participants With No Histologic Evidence of Vulvar HSIL and No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples	A treatment responder for the primary endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or vulvar low grade squamous intraepithelial lesions (LSIL) [vulval intraepithelial neoplasia 1 (VIN1)] or condyloma) and no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.	Week 48

Measure	Description	Time Frame
Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose	An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. A TEAE was defined per protocol as any AE with onset after the administration of study medication through the end of the study (i.e., study discharge).

Name	Affiliation	Role
Jeffrey Skolnik, MD	Inovio Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Christiana Care Health Systems		Newark	Delaware	19713	United States
Augusta University

ID	Title	Description
FG000	VGX-3100 + EP	Participants with histologically confirmed vulvar high-grade squamous intraepithelial lesion (HSIL) associated with human papilloma virus (HPV) 16 and/or 18, received four doses of 6 mg VGX-3100 as an intramuscular (IM) injection on Day 0, Week 4, Week 12, and Week 24 followed by electroporation (EP) using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 19, 2019	Jul 14, 2023

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

A treatment responder for the primary endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or vulvar low grade squamous intraepithelial lesions (LSIL) [vulval intraepithelial neoplasia 1 (VIN1)] or condyloma) and no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.

mITT population included all participants who received at least 1 dose of VGX-3100 + EP (with or without imiquimod) and had an analysis endpoint of interest. 'Overall number of participants analyzed' indicates the number of participants with data available for outcome measure analysis.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Units	Counts
Participants	OG00020 OG0018

Title

Denominators

Categories

Title	Measurements
	OG00015.0(3.2 to 37.9) OG00137.5(8.5 to 75.5)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		Clopper Pearson	A 1-sided p-value was calculated to prove superiority over historical control of 2%. Superiority of VGX-3100 alone was declared if p-value is <0.025.	0.0071														Superiority
OG001		Clopper Pearson

Secondary

Percentage of Participants With at Least One Local and Systemic Treatment-emergent Adverse Event (TEAE) During 7 Days Following Each Dose

An adverse event (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product. A TEAE was defined per protocol as any AE with onset after the administration of study medication through the end of the study (i.e., study discharge).

Safety population included all participants who received at least one (1) dose of VGX-3100 (with or without EP).

Posted

Number

95% Confidence Interval

percentage of participants

7 days following each dose: Day 0 (Days 0 to 7), Week 4 (Days 22 to 28), Week 12 (Days 78 to 84), Week 24 (Days 162 to 168), and Week 52 (Days 358 to 364)

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Secondary

Percentage of Participants With Adverse Events (AEs)

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body, or worsening of a pre-existing condition, temporally associated with the use of a product whether or not considered related to the use of the product.

Safety population included all participants who received at least 1 dose of VGX-3100 (with or without EP).

Posted

Number

percentage of participants

From baseline up to Week 100

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Secondary

Percentage of Participants With No Histologic Evidence of Vulvar HSIL

Participants with no histologic evidence of vulvar HSIL (normal tissue or vulvar LSIL [VIN1] or condyloma) based on histology (i.e. biopsies or excisional treatment) were considered. All lesions were evaluated for histologic evidence of vulvar HSIL.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Secondary

Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Vulvar Tissue Samples

Participants with no evidence of HPV-16 and/or HPV-18 indicated the clearance of the specific HPV genotypes [16, 18, or both]. All lesions were evaluated for evidence of HPV-16/18 in vulvar tissue.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.

Secondary

Percentage of Participants With No Histologic Evidence of Vulvar HSIL or No Evidence of HPV-16/18 in Vulvar Tissue

A treatment responder for the endpoint was defined as a participant with no histologic evidence of vulvar HSIL (normal tissue or LSIL [VIN1] or condyloma) based on histology (i.e. biopsies or excisional treatment) or no evidence of HPV-16 or HPV-18 (i.e., elimination of the specific genotypes [16, 18, or both]) in vulvar tissue at evaluation and who did not receive any non-study related treatment for vulvar HSIL. All lesions were evaluated for histologic evidence of vulvar HSIL or evidence of HPV-16/18 in vulvar tissue.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod

Secondary

Percentage of Participants With No Evidence of Vulvar HSIL, No Evidence of Vulvar LSIL (VIN1), and No Evidence of Condyloma on Histology

Histologic regression was defined as a participant with no histologic evidence of vulvar HSIL, no evidence of LSIL (VIN1), and no evidence of condyloma. Histologic regression of vulvar HSIL to normal tissue was assessed.

Posted

Number

95% Confidence Interval

percentage of participants

Week 48

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.

Secondary

Percentage of Participants With No Progression of Vulvar HSIL to Vulvar Cancer

Non-progression of vulvar HSIL to vulvar cancer was evaluated from baseline to Week 48. Progression was defined as advancement to carcinoma by histology.

Posted

Number

95% Confidence Interval

percentage of participants

From baseline up to Week 48

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Secondary

Percent Change From Baseline in the Cumulative Surface Area of the Acetowhite Vulvar Lesion(s)

Lesion(s), defined as areas that stain acetowhite were assessed. Analysis of qualifying lesions was defined as the change in total surface area of only lesions with both baseline and Week 48 measurements. Percent change in the cumulative surface area of the acetowhite vulvar lesion(s) was determined by the quantitative analysis of standardized prebiopsy photographic imaging of qualifying lesion(s) at Week 48 compared to baseline.

Posted

Mean

Standard Deviation

percent change in surface area

From baseline to Week 48

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Secondary

Change From Baseline in Interferon-Gamma (IFN-γ) Response Magnitude

Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood samples. Assessment of cellular immune activity was performed by IFN-γ enzyme-linked immunosorbent spot-forming (ELISpot) assay.

Posted

Median

Full Range

spot forming units (SFU) per 10^6 cells

Baseline; Weeks 15, 27, 48, 74, and 96

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Secondary

Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations

A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.

Posted

Geometric Mean

Standard Deviation

reciprocal endpoint titer

Weeks 15, 27, 48, 74, and 96

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Secondary

Change From Baseline in Flow Cytometry Response Magnitude

Assessment of cellular immune activity was measured using the application of flow cytometry for the purpose of performing a Lytic Granule Loading Assay. The Lytic Granule Loading Assay examines the following external cellular markers: cluster of differentiation 3 (CD3), CD4, CD8 (T-cell identification), CD137, CD38, and CD69 (T-cell activation markers) as well as PD-1 (exhaustion/activation marker). Here, a change from baseline in CD8+/CD137+ PBMCs expressing Perforin+ was reported.

Posted

Median

Full Range

SFU/10^6 PBMC

Baseline; Week 27

ID	Title	Description
OG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
OG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Palpitations	Cardiac disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0011 affected8 at risk
Vision blurred	Eye disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Nausea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG00010 affected25 at risk EG0013 affected8 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected25 at risk EG0011 affected8 at risk
Vomiting	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0011 affected8 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Injection site pain	General disorders	MedDRA 23.0	Systematic Assessment	EG00018 affected25 at risk EG0016 affected8 at risk
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG00014 affected25 at risk EG0014 affected8 at risk
Injection site swelling	General disorders	MedDRA 23.0	Systematic Assessment	EG0009 affected25 at risk EG0013 affected8 at risk
Injection site erythema	General disorders	MedDRA 23.0	Systematic Assessment	EG0008 affected25 at risk EG0013 affected8 at risk
Injection site bruising	General disorders	MedDRA 23.0	Systematic Assessment	EG00010 affected25 at risk EG0010 affected8 at risk
Injection site pruritis	General disorders	MedDRA 23.0	Systematic Assessment	EG0005 affected25 at risk EG0010 affected8 at risk
Malaise	General disorders	MedDRA 23.0	Systematic Assessment	EG0004 affected25 at risk EG0010 affected8 at risk
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0012 affected8 at risk
Influenza like illness	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0012 affected8 at risk
Application site pain	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Injection site haemorrhage	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Urinary tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Gastroenteritis	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Pneumonia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Procedural pain	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0003 affected25 at risk EG0010 affected8 at risk
Vulvovaginal injury	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Body temperature increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0003 affected25 at risk EG0010 affected8 at risk
Weight increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0011 affected8 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG00012 affected25 at risk EG0014 affected8 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0006 affected25 at risk EG0013 affected8 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG00010 affected25 at risk EG0013 affected8 at risk
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0004 affected25 at risk EG0011 affected8 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Paraesthesia	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0011 affected8 at risk
Depression	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0012 affected8 at risk
Anxiety	Psychiatric disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Urinary incontinence	Renal and urinary disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Vulvovaginal pruritis	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0005 affected25 at risk EG0012 affected8 at risk
Vulvovaginal discomfort	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected25 at risk EG0011 affected8 at risk
Vulval disorder	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected25 at risk EG0010 affected8 at risk
Dyspareunia	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Vulvovaginal burning sensation	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0011 affected8 at risk
Vulvovaginal pain	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0011 affected8 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Perineal pain	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Vulvovaginal erythema	Reproductive system and breast disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0011 affected8 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0011 affected8 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Wheezing	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 affected25 at risk EG0012 affected8 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 affected25 at risk EG0011 affected8 at risk
Hypertension	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0003 affected25 at risk EG0012 affected8 at risk
Hot flush	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0002 affected25 at risk EG0010 affected8 at risk

ID	Term
D000634	Aminoquinolines
D011804	Quinolines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Title	Description
BG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.
BG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52. In addition, participants applied imiquimod 5% cream to the vulvar lesion three times per week for 20 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	VGX-3100 + EP	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.	0	25	3	25	23	25
EG001	VGX-3100 + EP + Imiquimod	Participants with histologically confirmed vulvar HSIL associated with HPV-16 and/or 18, received four doses of 6 mg VGX-3100 as an IM injection on Day 0, Week 4, Week 12, and Week 24 followed by EP using the CELLECTRA™ 2000 device. Participants with vulvar HSIL who had a reduction in lesion size or no increase in lesion size at Week 48, received a fifth dose of VGX-3100 at Week 52.	0	8	0	8	8	8