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.

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.

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.

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.

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.

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.

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 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.

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.

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.

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.

ITT population included all participants who were randomized.

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 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.

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 included all participants who were randomized.

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 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.

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.

ITT population included all participants who were randomized.

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 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.

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.

ITT population included all participants who were randomized.

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.

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.

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.

ITT population included all participants who were randomized.

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 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.

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.

ITT population included all participants who were randomized.

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 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.

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.

ITT population included all participants who were randomized.

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 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.

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.

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.

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=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.

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.

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.

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.

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.

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 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.