Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Uterine Cervical Dysplasia

Squamous Intraepithelial Lesions of the Cervix

Carcinoma

Carcinoma, Squamous Cell

Carcinoma in Situ

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Cervical Intraepithelial Neoplasia

Participants received three IM injections of 6 milligram (mg) (in 1 milliliter \[mL\]) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

Participants received three IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

1 mL VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

VGX-3100

1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

Placebo

Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.

Electroporation (EP)

Jeffrey Skolnik, MD

HPV-301 is a prospective, randomized, double-blind, placebo controlled Phase 3 study to determine the efficacy, safety, and tolerability of VGX-3100 administered by intramuscular (IM) injection followed by electroporation (EP) delivered with CELLECTRA™ 5PSP in adult women with histologically confirmed cervical high grade squamous intraepithelial lesion (HSIL) (cervical intraepithelial neoplasia grade 2 \[CIN2\] or grade 3 \[CIN3\]) associated with human papillomavirus (HPV) 16 and/or HPV-18.

REVEAL 1 (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

Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame, and participants in which excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or low-grade intraepithelial lesion (LSIL). Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

Participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL at Week 36 and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined by histology as negative, squamous atypia, or LSIL.

Participants with no evidence of HPV-16 and/or HPV-18 at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. Cervical samples for HPV-16 and/or HPV-18 were collected using the ThinPrep®.

Participants with no histologic evidence of cervical HSIL, squamous atypia, or LSIL at the Week 36 time frame and participants in which an excision or biopsy sample was not obtained between the initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of cervical squamous intraepithelial neoplasia 1 (CIN1), CIN2, or CIN3 on biopsies or excisional treatment.

Participants with no histologic evidence of cervical HSIL, squamous atypia, and LSIL, no evidence of HPV-16 and/or HPV-18 by type specific HPV testing at the Week 36 time, and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered to be responders. No evidence of HSIL was defined as no evidence of CIN1, CIN2, or CIN3 on biopsies or excisional treatment.

Participants with no histologic evidence of cervical Adenocarcinoma in situ or cervical carcinoma at the Week 36 timeframe relative to baseline and participants in which an excision or biopsy sample was not obtained between initial dose up to Week 36 were considered as responders.

Participants with no evidence of HPV-16 and/or HPV-18 on specimens from noncervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 time frame were considered as responder.

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

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.

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

Inovio Pharmaceuticals

Safety set included all participants who received at least one dose of clinical trial treatment. One participant received mixed treatment and was excluded from the safety analysis.

Participants received three IM injections of 6 mg (in 1 mL) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

VGX-3100 + Electroporation (EP)

Placebo + EP

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

American Indian or Alaska Native

Asian

Black or African American

Native Hawaiian or Other Pacific Islander

White

Other

Multiple

Missing

Race/Ethnicity, Customized

ITT population included all participants who were randomized.

Study Director

Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples

Number of Participants with any AE

Number of Participants with any SAE

Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study

Percentage of Participants With No Evidence of Cervical HSIL on Histology

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

Percentage of Participants With No Evidence of LSIL or HSIL on Histology

Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18

Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma

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

HPV-16 E7 at Week 15

HPV-16 E7 at Week 36

HPV-18 E7 at Week 15

HPV-18 E7 at Week 36

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

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

HPV-16 E6: Baseline

HPV-16 E6: Change from Baseline at Week 15

HPV-16 E6: Change from Baseline at Week 36

HPV-16 E7: Baseline

HPV-16 E7: Change from Baseline at Week 15

HPV-16 E7: Change from Baseline at Week 36

HPV-18 E6: Baseline

HPV-18 E6: Change from Baseline at Week 15

HPV-18 E6: Change from Baseline at Week 36

HPV-18 E7: Baseline

HPV-18 E7: Change from Baseline at Week 15

HPV-18 E7: Change from Baseline at Week 36

Change From Baseline in Interferon-Gamma Response Magnitude

CD8+CD137+Perforin+: Baseline

CD8+CD137+Perforin+: Change from Baseline at Week 15

CD8+CD38+Perforin+: Baseline

CD8+CD38+Perforin+: Change from Baseline at Week 15

CD8+CD69+Perforin+: Baseline

CD8+CD69+Perforin+: Change from Baseline at Week 15

Change From Baseline in Flow Cytometry Response Magnitude

Overall Study

IM injections with VGX-3100 followed by electroporation (EP) using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.

IM injections with matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.

1 milliLiter (mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

CELLECTRA™-5PSP is used for EP following IM injection of VGX 3100 or placebo on Day 0, Week 4 and Week 12.

CELLECTRA™-5PSP

HPV-303 is a prospective, randomized, double-blind, placebo-controlled phase 3 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 HPV-16 and/or HPV-18.

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

Randomized Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL

Participants will be evaluated for evidence of cervical HSIL on histology as well as evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. An SAE is any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.

Participants will be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.

Participants will be evaluated for evidence of cervical HSIL on histology at the Week 36 visit.

Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of cervical intraepithelial neoplasia grade 1 \[CIN1\], CIN2 or CIN3) on histology at the Week 36 visit.

Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of CIN1, CIN2 or CIN3) on histology and be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.

Participants will be evaluated for progression of cervical HSIL to cervical carcinoma from baseline on histology at the Week 36 visit.

Participants will be evaluated for HPV-16 and/or HPV-18 status in specimens from non-cervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 Visit.

Interferon-gamma response magnitudes will be determined using the ELISpot assay at baseline, Weeks 15 and 36 visits.

Using flow cytometry cellular immune response magnitudes will be determined at the baseline and Week 15 visits.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)	NCT03185013	Cervical Dyspla... Cervical High G... HSIL	VGX-3100 Placebo Electroporation...	18 Years -	Inovio Pharmaceuticals
REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)	NCT03185013	Cervical Dyspla... Cervical High G... HSIL	VGX-3100 Placebo Electroporation...	18 Years -	Inovio Pharmaceuticals
REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)	NCT03721978	Cervical Dyspla... Cervical High G... HSIL	VGX-3100 Placebo CELLECTRA™-5PSP	18 Years -	Inovio Pharmaceuticals

Spots Global Cancer Trial Database for high grade squamous intraepithelial lesion (hsil)