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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
203
1 milliliter (mL) VGX-3100 injected IM.
1 mL of matched Placebo injected IM.
CELLECTRA™-5PSP used for EP following IM injection of VGX 3100.
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
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
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.
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Tucson, Arizona, United States
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Danbury, Connecticut, United States
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Newark, Delaware, United States
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Lake Worth, Florida, United States
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Miramar, Florida, United States
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Sunrise, Florida, United States
Augusta University
Augusta, Georgia, United States
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Oak Brook, Illinois, United States
Praetorian Pharmaceutical Research, LLC
Marrero, Louisiana, United States
Unified Women's Clinical Research - Hagerstown
Hagerstown, Maryland, United States
...and 43 more locations
Time frame: From Baseline to Week 40
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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