REVEAL 2 Trial (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

Randomized Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL

HPV-303 is a prospective, randomized, double-blind, placebo-controlled phase 3 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 HPV-16 and/or HPV-18.

Study Overview

• Status: Completed
• Conditions: Cervical Dysplasia; Cervical High Grade Squamous Intraepithelial Lesion; HSIL
• Intervention / Treatment: Biological: VGX-3100; Device: CELLECTRA™-5PSP; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 203
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina, C1181ACH
    • Hospital Italiano de Buenos Aires
  • Ramos Mejía, Argentina, B1704ETD
    • DIM Clínica Privada
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000PBB
      • Instituto de Ginecología
• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40420-000
      • Associacao Obras Sociais Irma Dulce Hospital Santo Antonio
  • Goiás
    • Goiânia, Goiás, Brazil, 74605-050
      • Hospital das Clínicas de Goiânia
  • Paraná
    • Curitiba, Paraná, Brazil, 80530-010
      • Hospital Erasto Gaertner
  • São Paulo
    • Jaú, São Paulo, Brazil, 17210-120
      • Hospital Amaral Carvalho
    • Ribeirao Preto, São Paulo, Brazil, 14048-900
      • Hospital Das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP
• Estonia
  • Tallinn, Estonia, 10119
    • East Tallinn Central Hospital Womens Clinic
  • Tartu, Estonia, 51014
    • Tartu University Hospital
  • Pärnumaa
    • Pärnu, Pärnumaa, Estonia, EE-80010
      • Parnu Hospital
• Finland
  • Kuopio, Finland, FI-70210
    • Northern Savo Hospital District Muncipal Federation
  • Uusimaa
    • Helsinki, Uusimaa, Finland, FI-00290
      • HUS Naistentaudit ja synnytykset
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Vilnius University Hospital Santaros Klinikos
  • Vilnius, Lithuania, LT-01117
    • Vilnius District Central Outpatient Clinic
• Poland
  • Śląskie, Poland, 40-611
    • Centrum Medyczne Angelius Provita
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-880
      • Niepubliczny Zakład Opieki Zdrowotnej Profimed
    • Lublin, Lubelskie, Poland, 20-880
      • Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • Puerto Rico Translational Research Center (PRTRC)
• South Africa
  • Gauteng
    • Centurion, Gauteng, South Africa, 0157
      • Lynette Reynders Private Practice
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • University of Cape Town
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañon
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe de Valencia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitario de Bellvitge
• United States
  • Arizona
    • Tucson, Arizona, United States, 85712
      • Visions Clinical Research- Tucson
  • Connecticut
    • Danbury, Connecticut, United States, 06810
      • Nuvance Health
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care Health System
  • Florida
    • Lake Worth, Florida, United States, 33461
      • Altus Research
    • Miramar, Florida, United States, 33027
      • Salom and Tangir LLC
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research, LLC
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Affinity Clinical Research Institute
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Praetorian Pharmaceutical Research, LLC
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Unified Women's Clinical Research - Hagerstown
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
  • Michigan
    • Saginaw, Michigan, United States, 48604
      • Saginaw Valley Medical Research Group LLC
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research Norfolk
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School
  • New York
    • Bronx, New York, United States, 10583
      • Montefiore Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Port Jefferson, New York, United States, 11777
      • Suffolk Obstetrics and Gynecology
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Unified Women's Clinical Research - Greensboro
    • Morehead City, North Carolina, United States, 28557
      • Unified Women's Clinical Research - Morehead City
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Clinical Research
  • Ohio
    • Columbus, Ohio, United States, 43213
      • ClinOhio Research Services
    • Fairfield, Ohio, United States, 45014
      • Obstetrics & Gynecology Associates, Inc.
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research-Smithfield
  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Venus Gynecology, LLC
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Women's Physician Group Suite 203
  • Texas
    • Sugar Land, Texas, United States, 77479
      • Storks Research
  • Virginia
    • Virginia Beach, Virginia, United States, 23456
      • Group For Women - Tidewater Clinical Research Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

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

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VGX-3100 + EP; IM injections with VGX-3100 followed by electroporation (EP) using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.	Biological: VGX-3100; 1 milliLiter (mL) VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.; Device: CELLECTRA™-5PSP; CELLECTRA™-5PSP is used for EP following IM injection of VGX 3100 or placebo on Day 0, Week 4 and Week 12.
Placebo Comparator: Placebo + EP; IM injections with matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4 and Week 12.	Device: CELLECTRA™-5PSP; CELLECTRA™-5PSP is used for EP following IM injection of VGX 3100 or placebo on Day 0, Week 4 and Week 12.; Biological: Placebo; 1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Baseline Biomarker-Positive Women with No Evidence of Cervical HSIL on Histology Sample and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36	Participants will be evaluated for evidence of cervical HSIL on histology as well as evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.	At Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Number of Baseline Biomarker-Positive Women and all Women with Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment and 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 to have a causal relationship with the treatment. An adverse event 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 adverse events. 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.	From baseline to Week 40
Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of HPV-16 and/or HPV-18 in Cervical Samples at Week 36	Participants will be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.	At Week 36
Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of Cervical HSIL on Histology Sample at Week 36	Participants will be evaluated for evidence of cervical HSIL on histology at the Week 36 visit.	At Week 36
Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of Low Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36	Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of cervical intraepithelial neoplasia grade 1 [CIN1], CIN2 or CIN3) on histology at the Week 36 visit.	At Week 36
Percentage of All Women with No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 at Week 36	Participants will be evaluated for evidence of cervical LSIL and HSIL (i.e. no evidence of CIN1, CIN2 or CIN3) on histology and be evaluated for evidence of HPV-16 and/or HPV-18 in cervical samples by type-specific HPV testing at the Week 36 visit.	At Week 36
Percentage of Baseline Biomarker-Positive Women and All Women with No Progression of Cervical HSIL to Cervical Carcinoma from Baseline at Week 36	Participants will be evaluated for progression of cervical HSIL to cervical carcinoma from baseline on histology at the Week 36 visit.	At Week 36
Percentage of Baseline Biomarker-Positive Women and All Women Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations at Week 36	Participants will be evaluated for HPV-16 and/or HPV-18 status in specimens from non-cervical anatomic locations (oropharynx, vagina and intra-anal) at the Week 36 Visit.	Baseline and Week 36
Among Baseline Biomarker-Positive Women and All Women Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations at Weeks 15 and 36		At Weeks 15 and 36
Among Baseline Biomarker-Positive Women and All Women Interferon-gamma Response Magnitudes at Baseline, Weeks 15 and 36	Interferon-gamma response magnitudes will be determined using the ELISpot assay at baseline, Weeks 15 and 36 visits.	At Baseline, Weeks 15 and 36
Among Baseline Biomarker-Positive Women and All Women Cellular Immune Response Magnitudes at Baseline and Week 15	Using flow cytometry cellular immune response magnitudes will be determined at the baseline and Week 15 visits.	At Baseline and Week 15

Collaborators and Investigators

• Sponsor: Inovio Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 9, 2019
• Primary Completion (Actual): August 23, 2022
• Study Completion (Actual): September 14, 2022

Study Registration Dates

• First Submitted: October 25, 2018
• First Submitted That Met QC Criteria: October 25, 2018
• First Posted (Actual): October 26, 2018

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 13, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: papillomavirus; Cervical intraepithelial neoplasia (CIN); CIN 2; CIN 3; Human papillomavirus (HPV); HPV-16; HPV-18; High Grade Squamous Intraepithelial Lesion (HSIL)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Neoplasms, Squamous Cell; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Carcinoma, Squamous Cell; Uterine Cervical Dysplasia; Squamous Intraepithelial Lesions of the Cervix
• Other Study ID Numbers: HPV-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes