Clinical trial NCT03185013: REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Dysplasia
Cervical High Grade Squamous Intraepithelial Lesion
HSIL
Keywords: Cervical intraepithelial neoplasia (CIN)
Human papillomavirus (HPV)
High grade squamous intraepithelial lesion (HSIL)
CIN 2
CIN 3
papillomavirus
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2017-06-14
Enrollment: 201
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples
timeFrame: Week 36
Secondary outcomes:
measure: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment for the Duration of the Study
timeFrame: From baseline up to Week 88
measure: Percentage of Participants With No Evidence of Cervical HSIL on Histology
timeFrame: Week 36
measure: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing
timeFrame: Week 36
measure: Percentage of Participants With No Evidence of LSIL or HSIL on Histology
timeFrame: Week 36
measure: Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18
timeFrame: Week 36
measure: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma
timeFrame: Week 36
measure: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations
timeFrame: Week 36
measure: Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations
timeFrame: Week 15 and Week 36
measure: Change From Baseline in Interferon-Gamma Response Magnitude
timeFrame: Baseline; Week 15 and Week 36
measure: Change From Baseline in Flow Cytometry Response Magnitude
timeFrame: Baseline, Week 15
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Mesa Obstetricians and Gynecologist
state: Arizona
city: Scottsdale
country: United States
facility: Women's Health Research
state: Arizona
city: Tucson
country: United States
facility: Visions Clinical Research-Tucson
state: Arizona
city: Clearwater
country: United States
facility: Women's Medical Research Group
state: Florida
city: Lake Worth
country: United States
facility: Altus Research
state: Florida
city: Miramar
country: United States
facility: Salom and Tangir LLC
state: Florida
city: West Palm Beach
country: United States
facility: Comprehensive Clinical Trials LLC
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Marrero
country: United States
facility: Praetorian Pharmaceutical Research, LLC
state: Louisiana
city: Saginaw
country: United States
facility: Saginaw Valley Medical Research Group LLC
state: Michigan
city: Norfolk
country: United States
facility: Meridian Clinical Research Norfolk
state: Nebraska
city: Newark
country: United States
facility: New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Port Jefferson
country: United States
facility: Suffolk Obstetrics and Gynecology
state: New York
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research, Inc.
state: South Carolina
city: Myrtle Beach
country: United States
facility: Magnolia Ob/Gyn Research Center, LLC
state: South Carolina
city: Chattanooga
country: United States
facility: Chattanooga Medical Research Inc
state: Tennessee
city: Memphis
country: United States
facility: Women's Physician Group
state: Tennessee
city: Houston
country: United States
facility: UAG Innovation Women Research, LLC
state: Texas
city: Norfolk
country: United States
facility: Group For Women
state: Virginia
city: Norfolk
country: United States
facility: Eastern Virginia Medical School
state: Virginia
city: Rosario
country: Argentina
facility: Instituto de Ginecología
state: Santa Fe
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Ramos Mejía
country: Argentina
facility: DIM Clínica Privada
city: Mons
country: Belgium
facility: Centre Hospitalier Universitaire Ambroise Paré
state: Hainaut
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
state: Limburg
city: Pärnu
country: Estonia
facility: Pärnu Hospital
state: Pärnumaa
city: Tallin
country: Estonia
facility: East Tallinn Central Hospital Womens Clinic
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Helsinki
country: Finland
facility: Kätilöopiston sairaala
city: Kuopio
country: Finland
facility: Lääkäriasema Cantti Oy
city: Essen
country: Germany
facility: Elisabeth Krankenhaus Essen GmbH
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Milano
country: Italy
facility: Istituto Nazionale Dei Tumori
city: Milan
country: Italy
facility: Istituto Europeo Di Oncologia
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
city: Vilnius
country: Lithuania
facility: Vilnius District Central Outpatient Clinic
city: Guadalajara
country: Mexico
facility: Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca
state: Jalisco
city: Lima
country: Peru
facility: Unidad de Ensayos Clinicos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos
city: Lima
country: Peru
facility: Liga Peruana De Lucha Contra El Cancer
city: Cebu
country: Philippines
facility: Perpetual Succour Hospital
city: Lublin
country: Poland
facility: Niepubliczny Zakład Opieki Zdrowotnej Profimed
state: Lubelskie
city: Lublin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
state: Lubelskie
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Coimbra
country: Portugal
facility: Centro Hospitalar E Universitário de Coimbra EPE
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria
city: Rio Piedras
country: Puerto Rico
facility: Puerto Rico Translational Research Center (PRTRC)
city: Dubnica Nad Váhom
country: Slovakia
facility: MCM GYNPED, s.r.o.
city: Martin
country: Slovakia
facility: Univerzitna nemocnica Martin
city: Centurion
country: South Africa
facility: Lynette Reynders Private Practice
state: Gauteng
city: Cape Town
country: South Africa
facility: University of Cape Town
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Bangkok
country: Thailand
facility: Chulalongkorn University
city: Bangkok
country: Thailand
facility: Siriraj Hospital Mahidol University
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary - PPDS
city: London
country: United Kingdom
facility: St Marys Hospital
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jeffrey Skolnik, MD
role: STUDY_DIRECTOR
References: