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

Cervical Dysplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03721978
• Other study ID #: HPV-303
• Status: Completed
• Phase: Phase 3
• Start date: April 9, 2019
• Est. completion date: September 14, 2022

Study information

• Verified date: October 2022
• Source: Inovio Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 203
• Est. completion date: September 14, 2022
• Est. primary completion date: August 23, 2022
• 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
• Cervical Intraepithelial Neoplasia
• HSIL
• Squamous Intraepithelial Lesions of the Cervix
• Uterine Cervical Dysplasia

Intervention

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.
• 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:
• CELLECTRA™-5PSP
CELLECTRA™-5PSP is used for EP following IM injection of VGX 3100 or placebo on Day 0, Week 4 and Week 12.

Locations

Country	Name	City	State
Argentina	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires
Argentina	DIM Clinica Privada	Ramos Mejía
Argentina	Instituto de Ginecología	Rosario	Santa Fe
Brazil	Hospital Erasto Gaertner	Curitiba	Paraná
Brazil	Hospital das Clinicas de Goiânia	Goiânia	Goiás
Brazil	Hospital Amaral Carvalho	Jaú	São Paulo
Brazil	Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP	Ribeirao Preto	São Paulo
Brazil	Associação Obras Sociais Irmã Dulce Hospital Santo Antônio	Salvador	Bahia
Estonia	Pärnu Hospital	Pärnu	Pärnumaa
Estonia	East Tallinn Central Hospital Womens Clinic	Tallinn
Estonia	Tartu University Hospital	Tartu
Finland	HUS Naistentaudit ja synnytykset	Helsinki	Uusimaa
Finland	Northern Savo Hospital District Muncipal Federation	Kuopio
Lithuania	Vilnius District Central Outpatient Clinic	Vilnius
Lithuania	Vilnius University Hospital Santaros Klinikos	Vilnius
Poland	Niepubliczny Zaklad Opieki Zdrowotnej Profimed	Lublin	Lubelskie
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin	Lubelskie
Poland	Centrum Medyczne Angelius Provita	Slaskie
Puerto Rico	Puerto Rico Translational Research Center (PRTRC)	Rio Piedras
South Africa	University of Cape Town	Cape Town	Western Cape
South Africa	Lynette Reynders Private Practice	Centurion	Gauteng
Spain	Hospital Universitario de Bellvitge	L'Hospitalet de Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United States	Augusta University	Augusta	Georgia
United States	Boston Medical Center	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	ClinOhio Research Services	Columbus	Ohio
United States	Nuvance Health	Danbury	Connecticut
United States	Obstetrics & Gynecology Associates, Inc.	Fairfield	Ohio
United States	Unified Women's Clinical Research - Greensboro	Greensboro	North Carolina
United States	Unified Women's Clinical Research - Hagerstown	Hagerstown	Maryland
United States	Altus Research	Lake Worth	Florida
United States	Praetorian Pharmaceutical Research, LLC	Marrero	Louisiana
United States	Women's Physician Group Suite 203	Memphis	Tennessee
United States	Salom and Tangir LLC	Miramar	Florida
United States	Unified Women's Clinical Research - Morehead City	Morehead City	North Carolina
United States	Venus Gynecology, LLC	Myrtle Beach	South Carolina
United States	Columbia University Medical Center	New York	New York
United States	Christiana Care Health System	Newark	Delaware
United States	New Jersey Medical School	Newark	New Jersey
United States	Meridian Clinical Research Norfolk	Norfolk	Nebraska
United States	Affinity Clinical Research Institute	Oak Brook	Illinois
United States	Suffolk Obstetrics and Gynecology	Port Jefferson	New York
United States	Saginaw Valley Medical Research Group LLC	Saginaw	Michigan
United States	Frontier Clinical Research-Smithfield	Smithfield	Pennsylvania
United States	Storks Research	Sugar Land	Texas
United States	Precision Clinical Research, LLC	Sunrise	Florida
United States	Visions Clinical Research- Tucson	Tucson	Arizona
United States	Group For Women - Tidewater Clinical Research Inc.	Virginia Beach	Virginia
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,  Brazil,  Estonia,  Finland,  Lithuania,  Poland,  Puerto Rico,  South Africa,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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