REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

Inovio Pharmaceuticals201 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

201

Conditions

Cervical Dysplasia Cervical High Grade Squamous Intraepithelial Lesion HSIL

Interventions

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (60)

Mesa Obstetricians and Gynecologist

Mesa, Arizona, United States

Women's Health Research

Scottsdale, Arizona, United States

Visions Clinical Research-Tucson

Tucson, Arizona, United States

Women's Medical Research Group

Clearwater, Florida, United States

Altus Research

Lake Worth, Florida, United States

Outcomes

Primary Outcomes

Percentage of Participants With No Evidence of Cervical HSIL on Histology 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 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®.

Time frame: Week 36

Secondary Outcomes

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

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.

Time frame: From baseline up to Week 88

Percentage of Participants With No Evidence of Cervical HSIL on Histology

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.

Time frame: Week 36

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 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®.

Time frame: Week 36

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

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.

Time frame: Week 36

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

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.

Time frame: Week 36

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

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.

Time frame: Week 36

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

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.

Time frame: Week 36

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.

Time frame: Week 15 and Week 36

Change From Baseline in Interferon-Gamma Response Magnitude

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.

Time frame: Baseline; Week 15 and Week 36

Change From Baseline in Flow Cytometry Response Magnitude

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.

Time frame: Baseline, Week 15