REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)
- Conditions
- Cervical DysplasiaCervical High Grade Squamous Intraepithelial LesionHSIL
- Interventions
- Biological: PlaceboBiological: VGX-3100Device: Electroporation (EP)
- Registration Number
- NCT03185013
- Lead Sponsor
- Inovio Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 201
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + EP Placebo 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. VGX-3100 + EP VGX-3100 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. VGX-3100 + EP Electroporation (EP) 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. Placebo + EP Electroporation (EP) 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples Week 36 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®.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Interferon-Gamma Response Magnitude Baseline; Week 15 and Week 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.
Percentage of Participants With No Evidence of Cervical HSIL on Histology Week 36 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.
Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations Week 15 and Week 36 A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.
Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 Week 36 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.
Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma Week 36 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.
Percentage of Participants With No Evidence of LSIL or HSIL on Histology Week 36 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.
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study From baseline up to Week 88 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.
Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing Week 36 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®.
Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations Week 36 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.
Change From Baseline in Flow Cytometry Response Magnitude Baseline, 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 change from baseline in CD8+CD137+Perforin+, CD8+CD38+Perforin+ and CD8+CD69+Perforin+ are reported.
Trial Locations
- Locations (60)
Women's Medical Research Group
🇺🇸Clearwater, Florida, United States
Altus Research
🇺🇸Lake Worth, Florida, United States
Praetorian Pharmaceutical Research, LLC
🇺🇸Marrero, Louisiana, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Greenville Pharmaceutical Research, Inc.
🇺🇸Greenville, South Carolina, United States
Hospital Italiano de Buenos Aires
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Elisabeth Krankenhaus Essen GmbH
🇩🇪Essen, Germany
Istituto Europeo Di Oncologia
🇮🇹Milan, Italy
Saginaw Valley Medical Research Group LLC
🇺🇸Saginaw, Michigan, United States
Lynette Reynders Private Practice
🇿🇦Centurion, Gauteng, South Africa
Centrum Medyczne Angelius Provita
🇵🇱Katowice, Poland
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Women's Physician Group
🇺🇸Memphis, Tennessee, United States
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Magnolia Ob/Gyn Research Center, LLC
🇺🇸Myrtle Beach, South Carolina, United States
Puerto Rico Translational Research Center (PRTRC)
🇵🇷Rio Piedras, Puerto Rico
Istituto Nazionale Dei Tumori
🇮🇹Milano, Italy
MCM GYNPED, s.r.o.
🇸🇰Dubnica Nad Váhom, Slovakia
Aberdeen Royal Infirmary - PPDS
🇬🇧Aberdeen, United Kingdom
University of Cape Town
🇿🇦Cape Town, South Africa
Hospital Universitario de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Mesa Obstetricians and Gynecologist
🇺🇸Mesa, Arizona, United States
UAG Innovation Women Research, LLC
🇺🇸Houston, Texas, United States
Women's Health Research
🇺🇸Scottsdale, Arizona, United States
Visions Clinical Research-Tucson
🇺🇸Tucson, Arizona, United States
Salom and Tangir LLC
🇺🇸Miramar, Florida, United States
Comprehensive Clinical Trials LLC
🇺🇸West Palm Beach, Florida, United States
Meridian Clinical Research Norfolk
🇺🇸Norfolk, Nebraska, United States
Suffolk Obstetrics and Gynecology
🇺🇸Port Jefferson, New York, United States
Chattanooga Medical Research Inc
🇺🇸Chattanooga, Tennessee, United States
DIM Clínica Privada
🇦🇷Ramos Mejía, Argentina
Universitätsklinikum Hamburg Eppendorf
🇩🇪Hamburg, Germany
Eastern Virginia Medical School
🇺🇸Norfolk, Virginia, United States
Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca
🇲🇽Guadalajara, Jalisco, Mexico
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Lazio, Italy
Vilnius University Hospital Santaros Klinikos
🇱🇹Vilnius, Lithuania
Unidad de Ensayos Clinicos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos
🇵🇪Lima, Peru
Liga Peruana De Lucha Contra El Cancer
🇵🇪Lima, Peru
Niepubliczny Zakład Opieki Zdrowotnej Profimed
🇵🇱Lublin, Lubelskie, Poland
Augusta University
🇺🇸Augusta, Georgia, United States
Centre Hospitalier Universitaire Ambroise Paré
🇧🇪Mons, Hainaut, Belgium
Tartu University Hospital
🇪🇪Tartu, Estonia
Kätilöopiston sairaala
🇫🇮Helsinki, Finland
Lääkäriasema Cantti Oy
🇫🇮Kuopio, Finland
Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
🇵🇹Lisboa, Portugal
Univerzitna nemocnica Martin
🇸🇰Martin, Slovakia
Siriraj Hospital Mahidol University
🇹🇭Bangkok, Thailand
Ziekenhuis Oost-Limburg
🇧🇪Genk, Limburg, Belgium
Pärnu Hospital
🇪🇪Pärnu, Pärnumaa, Estonia
Instituto de Ginecología
🇦🇷Rosario, Santa Fe, Argentina
East Tallinn Central Hospital Womens Clinic
🇪🇪Tallin, Estonia
Vilnius District Central Outpatient Clinic
🇱🇹Vilnius, Lithuania
Perpetual Succour Hospital
🇵🇭Cebu, Philippines
Centro Hospitalar E Universitário de Coimbra EPE
🇵🇹Coimbra, Portugal
Chulalongkorn University
🇹🇭Bangkok, Thailand
Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
🇵🇱Lublin, Lubelskie, Poland
St Marys Hospital
🇬🇧London, United Kingdom
Group For Women
🇺🇸Norfolk, Virginia, United States
New Jersey Medical School
🇺🇸Newark, New Jersey, United States
Lyndhurst Clinical Research
🇺🇸Winston-Salem, North Carolina, United States