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

NCT03721978 | Completed Phase 3 Results DMC FDA Drug FDA Device

• 2 other identifiers: HPV-3032018-004114-17
• Study Type: interventional
• Target: 203
• Locations: 9 countries
• Sites: 48

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.

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

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline biomarker-positive participants with no histologic (i.e., biopsies or excisional treatment) evidence of cervical HSIL, no evidence of HPV-16 and/or HPV-18 at Week 36, and participants who did not have unscheduled excision or biopsy sample 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™. The efficacy time frame is defined by a biopsy or surgical excision at any time starting from 14 days prior to the protocol-specified target date of Week 36. The first tissue removal sample within the time frame determines the histology endpoint.

  At Week 36

Secondary Outcomes (23)

• Baseline Biomarker-positive Participants for Safety Population: Number of Participants With Any Local and Systemic Adverse Events (AEs)

  From Baseline to Week 40

• Safety Population: Number of Participants With Local and Systemic AEs

  From Baseline to Week 40

• 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])

  From Baseline to Week 40

• Safety Population: Number of Participants With Any TEAEs and Serious TEAEs (Including SUSAR and UADE)

  From Baseline to Week 40

• 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

  At Week 36

Study Arms (2)

VGX-3100 + EP

EXPERIMENTAL

Participants received 3 IM injections of 6 mg (in 1 mL) VGX-3100 followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

Biological: VGX-3100; Device: CELLECTRA™-5PSP

Matched Placebo + EP

PLACEBO COMPARATOR

Participants received 3 IM injections of 1 mL VGX-3100 matching placebo followed by EP using the CELLECTRA™-5PSP device on Day 0, Week 4, and Week 12.

Biological: Matched Placebo; Device: CELLECTRA™-5PSP

Interventions

VGX-3100 BIOLOGICAL

1 milliliter (mL) VGX-3100 injected IM.

VGX-3100 + EP

Matched Placebo BIOLOGICAL

1 mL of matched Placebo injected IM.

Matched Placebo + EP

CELLECTRA™-5PSP DEVICE

CELLECTRA™-5PSP used for EP following IM injection of VGX 3100.

Matched Placebo + EP; VGX-3100 + EP

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Inovio Pharmaceuticals: lead

Study Sites (53)

Visions Clinical Research- Tucson

Tucson, Arizona, 85712, United States

Location

Nuvance Health

Danbury, Connecticut, 06810, United States

Location

Christiana Care Health System

Newark, Delaware, 19713, United States

Location

Altus Research

Lake Worth, Florida, 33461, United States

Location

Salom and Tangir LLC

Miramar, Florida, 33027, United States

Location

Precision Clinical Research, LLC

Sunrise, Florida, 33351, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Affinity Clinical Research Institute

Oak Brook, Illinois, 60523, United States

Location

Praetorian Pharmaceutical Research, LLC

Marrero, Louisiana, 70072, United States

Location

Unified Women's Clinical Research - Hagerstown

Hagerstown, Maryland, 21740, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Saginaw Valley Medical Research Group LLC

Saginaw, Michigan, 48604, United States

Location

Meridian Clinical Research Norfolk

Norfolk, Nebraska, 68701, United States

Location

New Jersey Medical School

Newark, New Jersey, 07103, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Suffolk Obstetrics and Gynecology

Port Jefferson, New York, 11777, United States

Location

Montefiore Medical Center

The Bronx, New York, 10583, United States

Location

Unified Women's Clinical Research - Greensboro

Greensboro, North Carolina, 27408, United States

Location

Unified Women's Clinical Research - Morehead City

Morehead City, North Carolina, 28557, United States

Location

Lyndhurst Clinical Research

Winston-Salem, North Carolina, 27103, United States

Location

ClinOhio Research Services

Columbus, Ohio, 43213, United States

Location

Obstetrics & Gynecology Associates, Inc.

Fairfield, Ohio, 45014, United States

Location

Frontier Clinical Research-Smithfield

Smithfield, Pennsylvania, 15478, United States

Location

Venus Gynecology, LLC

Myrtle Beach, South Carolina, 29572, United States

Location

Women's Physician Group Suite 203

Memphis, Tennessee, 38119, United States

Location

Storks Research

Sugar Land, Texas, 77479, United States

Location

Group For Women - Tidewater Clinical Research Inc.

Virginia Beach, Virginia, 23456, United States

Location

Instituto de Ginecología

Rosario, Santa Fe Province, S2000PBB, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, C1181ACH, Argentina

Location

DIM Clinica Privada

Ramos Mejía, B1704ETD, Argentina

Location

Associação Obras Sociais Irmã Dulce Hospital Santo Antônio

Salvador, Estado de Bahia, 40420-000, Brazil

Location

Hospital das Clinicas de Goiânia

Goiânia, Goiás, 74605-050, Brazil

Location

Hospital Erasto Gaertner

Curitiba, Paraná, 80530-010, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-120, Brazil

Location

Hospital Das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Pärnu Hospital

Pärnu, Pärnumaa, EE-80010, Estonia

Location

East Tallinn Central Hospital Womens Clinic

Tallinn, 10119, Estonia

Location

Tartu University Hospital

Tartu, 51014, Estonia

Location

HUS Naistentaudit ja synnytykset

Helsinki, Uusimaa, FI-00290, Finland

Location

Northern Savo Hospital District Muncipal Federation

Kuopio, FI-70210, Finland

Location

Vilnius District Central Outpatient Clinic

Vilnius, LT-01117, Lithuania

Location

Vilnius University Hospital Santaros Klinikos

Vilnius, LT-08661, Lithuania

Location

Niepubliczny Zakład Opieki Zdrowotnej Profimed

Lublin, Lublin Voivodeship, 20-880, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie

Lublin, Lublin Voivodeship, 20-880, Poland

Location

Centrum Medyczne Angelius Provita

Śląskie, 40-611, Poland

Location

Puerto Rico Translational Research Center (PRTRC)

Rio Piedras, 00935, Puerto Rico

Location

Lynette Reynders Private Practice

Centurion, Gauteng, 0157, South Africa

Location

University of Cape Town

Cape Town, Western Cape, 7925, South Africa

Location

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28009, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Uterine Cervical Dysplasia; Squamous Intraepithelial Lesions

Interventions

VGX-3100

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Morphological and Microscopic Findings; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Study Director
• Organization: Inovio Pharmaceuticals

clinical.trials@inovio.com

267-440-4237

Study Officials

• Jeffrey Skolnik, MD

  Inovio Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 25, 2018
• First Posted: October 26, 2018
• Study Start: February 28, 2019
• Primary Completion: August 23, 2022
• Study Completion: September 15, 2022
• Last Updated: October 17, 2024
• Results First Posted: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

AR (3); ES (3); FI (2); LI (2); PR (1); US (27); BR (5); PL (3); ZA (2)