REVEAL 1 (Evaluation of VGX-3100 and Electroporation for the Treatment of Cervical HSIL)

Cervical Dysplasia Clinical Trial

— REVEAL 1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03185013
• Other study ID #: HPV-301
• Secondary ID: 2016-002761-63
• Status: Completed
• Phase: Phase 3
• Start date: June 28, 2017
• Est. completion date: April 6, 2021

Study information

• Verified date: July 2023
• Source: Inovio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 201
• Est. completion date: April 6, 2021
• Est. primary completion date: July 8, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma in Situ
• Carcinoma, Squamous Cell
• Cervical Dysplasia
• Cervical High Grade Squamous Intraepithelial Lesion
• HSIL
• Squamous Intraepithelial Lesions of the Cervix
• Uterine Cervical Dysplasia

Intervention

Biological:
• VGX-3100
1 mL VGX-3100 will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.
• Placebo
1 mL of Placebo will be injected IM and delivered by EP using CELLECTRA™-5PSP on Day 0, Week 4 and Week 12.

Device:
• Electroporation (EP)
Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires
Argentina	DIM Clínica Privada	Ramos Mejía
Argentina	Instituto de Ginecología	Rosario	Santa Fe
Belgium	Ziekenhuis Oost-Limburg	Genk	Limburg
Belgium	Centre Hospitalier Universitaire Ambroise Paré	Mons	Hainaut
Estonia	Pärnu Hospital	Pärnu	Pärnumaa
Estonia	East Tallinn Central Hospital Womens Clinic	Tallin
Estonia	Tartu University Hospital	Tartu
Finland	Kätilöopiston sairaala	Helsinki
Finland	Lääkäriasema Cantti Oy	Kuopio
Germany	Elisabeth Krankenhaus Essen GmbH	Essen
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Italy	Istituto Europeo Di Oncologia	Milan
Italy	Istituto Nazionale Dei Tumori	Milano
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Lithuania	Vilnius District Central Outpatient Clinic	Vilnius
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Mexico	Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca	Guadalajara	Jalisco
Peru	Liga Peruana De Lucha Contra El Cancer	Lima
Peru	Unidad de Ensayos Clinicos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos	Lima
Philippines	Perpetual Succour Hospital	Cebu
Poland	Centrum Medyczne Angelius Provita	Katowice
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Profimed	Lublin	Lubelskie
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin	Lubelskie
Portugal	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra
Portugal	Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria	Lisboa
Puerto Rico	Puerto Rico Translational Research Center (PRTRC)	Rio Piedras
Slovakia	MCM GYNPED, s.r.o.	Dubnica Nad Váhom
Slovakia	Univerzitna nemocnica Martin	Martin
South Africa	University of Cape Town	Cape Town
South Africa	Lynette Reynders Private Practice	Centurion	Gauteng
Spain	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Thailand	Chulalongkorn University	Bangkok
Thailand	Siriraj Hospital Mahidol University	Bangkok
United Kingdom	Aberdeen Royal Infirmary - PPDS	Aberdeen
United Kingdom	St Marys Hospital	London
United States	Augusta University	Augusta	Georgia
United States	Chattanooga Medical Research Inc	Chattanooga	Tennessee
United States	Women's Medical Research Group	Clearwater	Florida
United States	Greenville Pharmaceutical Research, Inc.	Greenville	South Carolina
United States	UAG Innovation Women Research, LLC	Houston	Texas
United States	Altus Research	Lake Worth	Florida
United States	Praetorian Pharmaceutical Research, LLC	Marrero	Louisiana
United States	Women's Physician Group	Memphis	Tennessee
United States	Mesa Obstetricians and Gynecologist	Mesa	Arizona
United States	Salom and Tangir LLC	Miramar	Florida
United States	Magnolia Ob/Gyn Research Center, LLC	Myrtle Beach	South Carolina
United States	Columbia University Medical Center	New York	New York
United States	New Jersey Medical School	Newark	New Jersey
United States	Eastern Virginia Medical School	Norfolk	Virginia
United States	Group For Women	Norfolk	Virginia
United States	Meridian Clinical Research Norfolk	Norfolk	Nebraska
United States	Suffolk Obstetrics and Gynecology	Port Jefferson	New York
United States	Saginaw Valley Medical Research Group LLC	Saginaw	Michigan
United States	Women's Health Research	Scottsdale	Arizona
United States	Visions Clinical Research-Tucson	Tucson	Arizona
United States	Comprehensive Clinical Trials LLC	West Palm Beach	Florida
United States	Lyndhurst Clinical Research	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Inovio Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Estonia,  Finland,  Germany,  Italy,  Lithuania,  Mexico,  Peru,  Philippines,  Poland,  Portugal,  Puerto Rico,  Slovakia,  South Africa,  Spain,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With No Evidence of Cervical HSIL on Histology and No Evidence of HPV-16 and/or HPV-18 in Cervical Samples	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®.	Week 36
Secondary	Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment 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 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.	From baseline up to Week 88
Secondary	Percentage of Participants With No Evidence of Cervical HSIL on Histology	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.	Week 36
Secondary	Percentage of Participants With No Evidence of HPV-16 and/or HPV-18 in Cervical Samples by Type Specific HPV Testing	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®.	Week 36
Secondary	Percentage of Participants With No Evidence of LSIL or HSIL on Histology	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.	Week 36
Secondary	Percentage of Participants With No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18	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.	Week 36
Secondary	Percentage of Participants With No Progression of Cervical HSIL to Cervical Carcinoma	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.	Week 36
Secondary	Percentage of Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations	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.	Week 36
Secondary	Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations	A standardized binding enzyme-linked immunosorbent assay (ELISA) was performed to measure the anti-HPV-16/18 antibody response induced by VGX-3100.	Week 15 and Week 36
Secondary	Change From Baseline in Interferon-Gamma Response Magnitude	Assessment of cellular immune activity occurred via the application of the Interferon-? enzyme-linked immunosorbent spot (IFN-? ELISpot). Peripheral blood mononuclear cells (PBMCs) isolated from whole blood sample were used for analysis.	Baseline; Week 15 and Week 36
Secondary	Change From Baseline in Flow Cytometry Response Magnitude	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.	Baseline, Week 15