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

Sponsor

Inovio Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03721978

Collaborator

(none)

203

Enrollment

Locations

Arms

40.8

Anticipated Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Dysplasia Cervical High Grade Squamous Intraepithelial Lesion HSIL	Biological: VGX-3100 Biological: Placebo Device: CELLECTRA™-5PSP	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

203 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 9, 2019

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Sep 1, 2022

Arms and Interventions

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.	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. 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.

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.

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.

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.

Outcome Measures

Primary Outcome Measures

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 [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.

Secondary Outcome Measures

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 [From baseline to Week 40]
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.
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 [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.
Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of Cervical HSIL on Histology Sample at Week 36 [At Week 36]
Participants will be evaluated for evidence of cervical HSIL on histology at the Week 36 visit.
Percentage of Baseline Biomarker-Positive Women and All Women with No Evidence of Low Grade Squamous Intraepithelial Lesion (LSIL) or HSIL at Week 36 [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.
Percentage of All Women with No Evidence of LSIL or HSIL and No Evidence of HPV-16 and/or HPV-18 at Week 36 [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.
Percentage of Baseline Biomarker-Positive Women and All Women with No Progression of Cervical HSIL to Cervical Carcinoma from Baseline at Week 36 [At Week 36]
Participants will be evaluated for progression of cervical HSIL to cervical carcinoma from baseline on histology at the Week 36 visit.
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 [Baseline and 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.
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 [At Baseline, Weeks 15 and 36]
Interferon-gamma response magnitudes will be determined using the ELISpot assay at baseline, Weeks 15 and 36 visits.
Among Baseline Biomarker-Positive Women and All Women Cellular Immune Response Magnitudes at Baseline and Week 15 [At Baseline and Week 15]
Using flow cytometry cellular immune response magnitudes will be determined at the baseline and Week 15 visits.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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