Clinical trial NCT03721978: REVEAL 2 Trial (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)
CIN 2
CIN 3
Human papillomavirus (HPV)
HPV-16
HPV-18
High Grade Squamous Intraepithelial Lesion (HSIL)
papillomavirus
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2018-10-26
Enrollment: 203
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-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.


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: 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
timeFrame: At Week 36
Secondary outcomes:
measure: Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)
timeFrame: From Baseline to Week 40
measure: Safety Population: Number of Participants With Local and Systemic AEs
timeFrame: From Baseline to Week 40
measure: 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])
timeFrame: From Baseline to Week 40
measure: Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)
timeFrame: From Baseline to Week 40
measure: 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
timeFrame: At Week 36
measure: Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample
timeFrame: At Week 36
measure: ITT Population: Percentage of Participants With No Histologic Evidence of Cervical HSIL on Histology Sample
timeFrame: At Week 36
measure: 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
timeFrame: At Week 36
measure: ITT Population: Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing
timeFrame: At Week 36
measure: Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Histologic Evidence of LSIL or HSIL on Histology Sample
timeFrame: At Week 36
measure: ITT Population: Percentage of Participants With No Evidence of Histologic LSIL or HSIL on Histology Sample
timeFrame: At Week 36
measure: 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
timeFrame: At Week 36
measure: 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
timeFrame: At Week 36
measure: Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma
timeFrame: From Baseline at Week 36
measure: ITT Population: Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma
timeFrame: From Baseline at Week 36
measure: Baseline Biomarker-positive Participants for ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations
timeFrame: From Baseline at Week 36
measure: ITT Population: Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations
timeFrame: From Baseline at Week 36
measure: Baseline Biomarker-positive Participants for mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody
timeFrame: At Week 15 and Week 36
measure: mITT Population: Serum Concentrations of Anti-HPV-16 and Anti-HPV-18 Antibody
timeFrame: At Week 15 and Week 36
measure: Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36
timeFrame: Baseline; Week 15 and Week 36
measure: mITT Population: Change From Baseline in Interferon-Gamma Response Magnitude at Week 15 and 36
timeFrame: Baseline; Week 15 and Week 36
measure: Baseline Biomarker-positive Participants for mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15
timeFrame: Baseline, Week 15
measure: mITT Population: Change From Baseline in Flow Cytometry Response Magnitude at Week 15
timeFrame: Baseline, Week 15
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Visions Clinical Research- Tucson
state: Arizona
city: Danbury
country: United States
facility: Nuvance Health
state: Connecticut
city: Newark
country: United States
facility: Christiana Care Health System
state: Delaware
city: Lake Worth
country: United States
facility: Altus Research
state: Florida
city: Miramar
country: United States
facility: Salom and Tangir LLC
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research, LLC
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Oak Brook
country: United States
facility: Affinity Clinical Research Institute
state: Illinois
city: Marrero
country: United States
facility: Praetorian Pharmaceutical Research, LLC
state: Louisiana
city: Hagerstown
country: United States
facility: Unified Women's Clinical Research - Hagerstown
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
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: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
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: Greensboro
country: United States
facility: Unified Women's Clinical Research - Greensboro
state: North Carolina
city: Morehead City
country: United States
facility: Unified Women's Clinical Research - Morehead City
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Columbus
country: United States
facility: ClinOhio Research Services
state: Ohio
city: Fairfield
country: United States
facility: Obstetrics & Gynecology Associates, Inc.
state: Ohio
city: Smithfield
country: United States
facility: Frontier Clinical Research-Smithfield
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Venus Gynecology, LLC
state: South Carolina
city: Memphis
country: United States
facility: Women's Physician Group Suite 203
state: Tennessee
city: Sugar Land
country: United States
facility: Storks Research
state: Texas
city: Virginia Beach
country: United States
facility: Group For Women - Tidewater Clinical Research Inc.
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 Clinica Privada
city: Salvador
country: Brazil
facility: Associação Obras Sociais Irmã Dulce Hospital Santo Antônio
state: Bahia
city: Goiânia
country: Brazil
facility: Hospital das Clinicas de Goiânia
state: Goiás
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Jaú
country: Brazil
facility: Hospital Amaral Carvalho
state: São Paulo
city: Ribeirao Preto
country: Brazil
facility: Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP
state: São Paulo
city: Pärnu
country: Estonia
facility: Pärnu Hospital
state: Pärnumaa
city: Tallinn
country: Estonia
facility: East Tallinn Central Hospital Womens Clinic
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Helsinki
country: Finland
facility: HUS Naistentaudit ja synnytykset
state: Uusimaa
city: Kuopio
country: Finland
facility: Northern Savo Hospital District Muncipal Federation
city: Vilnius
country: Lithuania
facility: Vilnius District Central Outpatient Clinic
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros Klinikos
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: Śląskie
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Rio Piedras
country: Puerto Rico
facility: Puerto Rico Translational Research Center (PRTRC)
city: Centurion
country: South Africa
facility: Lynette Reynders Private Practice
state: Gauteng
city: Cape Town
country: South Africa
facility: University of Cape Town
state: Western Cape
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
Study officials:
affiliation: Inovio Pharmaceuticals
name: Jeffrey Skolnik, MD
role: STUDY_DIRECTOR
References: