- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03185013
REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL) (REVEAL 1)
July 24, 2023 updated by: Inovio Pharmaceuticals
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
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 Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
201
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ciudad Autonoma de Buenos Aires, Argentina, C1181ACH
- Hospital Italiano de Buenos Aires
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Ramos Mejía, Argentina, B1704ETD
- DIM Clínica Privada
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Santa Fe
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Rosario, Santa Fe, Argentina, S2000PBB
- Instituto de Ginecología
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Hainaut
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Mons, Hainaut, Belgium, 7000
- Centre Hospitalier Universitaire Ambroise Pare
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Limburg
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Genk, Limburg, Belgium, 3600
- Ziekenhuis Oost-Limburg
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Tallin, Estonia, 10119
- East Tallinn Central Hospital Womens Clinic
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Tartu, Estonia, 51014
- Tartu University Hospital
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Pärnumaa
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Pärnu, Pärnumaa, Estonia, EE-80010
- Parnu Hospital
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Helsinki, Finland, 290
- Kätilöopiston sairaala
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Kuopio, Finland, FI-70110
- Lääkäriasema Cantti Oy
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Essen, Germany, 45138
- Elisabeth Krankenhaus Essen GmbH
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Hamburg, Germany, 20246
- Universitätsklinikum Hamburg Eppendorf
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Milan, Italy, 20141
- Istituto Europeo di Oncologia
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Milano, Italy, 20133
- Istituto Nazionale dei Tumori
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Lazio
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Roma, Lazio, Italy, 00168
- Fondazione Policlinico Universitario A Gemelli
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Vilnius, Lithuania, LT- 08661
- Vilnius University hospital Santaros klinikos
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Vilnius, Lithuania, LT-01117
- Vilnius District Central Outpatient Clinic
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Jalisco
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Guadalajara, Jalisco, Mexico, 44340
- Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca
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Lima, Peru, 15083
- Unidad de Ensayos Clinicos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos
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Lima, Peru, 15084
- Liga Peruana De Lucha Contra El Cancer
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Cebu, Philippines, 6000
- Perpetual Succour Hospital
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Katowice, Poland, 40-611
- Centrum Medyczne Angelius Provita
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Lubelskie
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Lublin, Lubelskie, Poland, 20-880
- Niepubliczny Zakład Opieki Zdrowotnej Profimed
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Lublin, Lubelskie, Poland, 20-880
- Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
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Coimbra, Portugal, 3000-075
- Centro Hospitalar e Universitario de Coimbra EPE
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Lisboa, Portugal, 1649-035
- Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
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Rio Piedras, Puerto Rico, 00935
- Puerto Rico Translational Research Center (PRTRC)
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Dubnica Nad Váhom, Slovakia, 018 41
- MCM GYNPED, s.r.o.
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Martin, Slovakia, 036 59
- Univerzitna nemocnica Martin
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Cape Town, South Africa, 7925
- University of Cape Town
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Gauteng
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Centurion, Gauteng, South Africa, 157
- Lynette Reynders Private Practice
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Madrid, Spain, 28040
- Hospital Clinico San Carlos
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Madrid, Spain, 28041
- Hospital Universitario 12 De Octubre
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Barcelona
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Hospitalet de Llobregat, Barcelona, Spain, 8907
- Hospital Universitario de Bellvitge
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Bangkok, Thailand, 10700
- Siriraj Hospital Mahidol University
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Bangkok, Thailand, 10700
- Chulalongkorn University
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Aberdeen, United Kingdom, AB25 7ZD
- Aberdeen Royal Infirmary - PPDS
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London, United Kingdom, W2 1NY
- St Marys Hospital
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Arizona
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Mesa, Arizona, United States, 85209
- Mesa Obstetricians and Gynecologist
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Scottsdale, Arizona, United States, 85251
- Women's Health Research
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Tucson, Arizona, United States, 85712
- Visions Clinical Research-Tucson
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Florida
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Clearwater, Florida, United States, 33759
- Women's Medical Research Group
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Lake Worth, Florida, United States, 33461
- Altus Research
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Miramar, Florida, United States, 33461
- Salom and Tangir LLC
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West Palm Beach, Florida, United States, 33409
- Comprehensive Clinical Trials LLC
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Georgia
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Augusta, Georgia, United States, 30912
- Augusta University
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Louisiana
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Marrero, Louisiana, United States, 70072
- Praetorian Pharmaceutical Research, LLC
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Michigan
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Saginaw, Michigan, United States, 48604
- Saginaw Valley Medical Research Group LLC
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Nebraska
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Norfolk, Nebraska, United States, 68701
- Meridian Clinical Research Norfolk
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New Jersey
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Newark, New Jersey, United States, 07103
- New Jersey Medical School
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New York
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New York, New York, United States, 10032
- Columbia University Medical Center
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Port Jefferson, New York, United States, 11777
- Suffolk Obstetrics and Gynecology
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North Carolina
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Winston-Salem, North Carolina, United States, 27103
- Lyndhurst Clinical Research
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South Carolina
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Greenville, South Carolina, United States, 29615
- Greenville Pharmaceutical Research, Inc.
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Myrtle Beach, South Carolina, United States, 29572
- Magnolia Ob/Gyn Research Center, LLC
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Tennessee
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Chattanooga, Tennessee, United States, 37404
- Chattanooga Medical Research Inc
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Memphis, Tennessee, United States, 38104
- Women's Physician Group
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Texas
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Houston, Texas, United States, 77074
- UAG Innovation Women Research, LLC
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Virginia
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Norfolk, Virginia, United States, 23507
- Eastern Virginia Medical School
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Norfolk, Virginia, United States, 23502
- Group For Women
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: VGX-3100 + 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.
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Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.
1 mL VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.
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Placebo Comparator: Placebo + 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.
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1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.
Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples
Time Frame: Week 36
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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®.
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Week 36
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study
Time Frame: From baseline up to Week 88
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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.
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From baseline up to Week 88
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Percentage of Participants With No Evidence of Cervical HSIL on Histology
Time Frame: Week 36
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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.
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Week 36
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Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing
Time Frame: Week 36
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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®.
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Week 36
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Percentage of Participants With No Evidence of LSIL or HSIL on Histology
Time Frame: Week 36
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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.
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Week 36
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Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18
Time Frame: Week 36
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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.
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Week 36
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Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma
Time Frame: Week 36
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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.
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Week 36
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Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations
Time Frame: Week 36
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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.
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Week 36
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Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
Time Frame: Week 15 and Week 36
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A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.
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Week 15 and Week 36
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Change From Baseline in Interferon-Gamma Response Magnitude
Time Frame: Baseline; Week 15 and Week 36
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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.
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Baseline; Week 15 and Week 36
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Change From Baseline in Flow Cytometry Response Magnitude
Time Frame: Baseline, Week 15
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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.
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Baseline, Week 15
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Jeffrey Skolnik, MD, Inovio Pharmaceuticals
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 28, 2017
Primary Completion (Actual)
July 8, 2020
Study Completion (Actual)
April 6, 2021
Study Registration Dates
First Submitted
June 9, 2017
First Submitted That Met QC Criteria
June 9, 2017
First Posted (Actual)
June 14, 2017
Study Record Updates
Last Update Posted (Actual)
July 27, 2023
Last Update Submitted That Met QC Criteria
July 24, 2023
Last Verified
July 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Uterine Cervical Diseases
- Uterine Diseases
- Precancerous Conditions
- Neoplasms, Squamous Cell
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Genital Diseases
- Genital Diseases, Female
- Carcinoma in Situ
- Carcinoma, Squamous Cell
- Uterine Cervical Dysplasia
- Squamous Intraepithelial Lesions of the Cervix
Other Study ID Numbers
- HPV-301
- 2016-002761-63 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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