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

Sponsor

Inovio Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT03185013

Collaborator

(none)

201

Enrollment

Locations

Arms

45.3

Actual Duration (Months)

3.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Dysplasia Cervical High Grade Squamous Intraepithelial Lesion HSIL	Biological: VGX-3100 Biological: Placebo Device: Electroporation (EP)	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

201 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 28, 2017

Actual Primary Completion Date :

Jul 8, 2020

Actual Study Completion Date :

Apr 7, 2021

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

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: Electroporation (EP)

Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.

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: Electroporation (EP)

Intramuscular injection followed by EP with the CELLECTRA™ 5PSP device.

Outcome Measures

Primary Outcome Measures

Percentage of Participants with No Evidence of Cervical HSIL on Histology 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 Participants with Any Adverse Events (AEs) and Serious Adverse Events (SAEs) Following Investigational Treatment and for the Duration of the Study [From baseline to Week 88]
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 Participants with No Evidence of Cervical HSIL at Week 36 [At Week 36]
Participants will be evaluated for evidence of cervical HSIL on histology at the Week 36 visit.
Percentage of Participants 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.
Percentage of Participants 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 LSIL (i.e. slightly abnormal cells on the surface of the cervix) or HSIL (i.e. evidence of cervical intraepithelial neoplasia grade 1 [CIN1], CIN2 or CIN3 on biopsies or excisional treatment) on histology at the Week 36 visit.
Percentage of Participants 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 LSIL (i.e. slightly abnormal cells on the surface of the cervix) or HSIL (i.e. evidence of CIN1, CIN2 or CIN3 on biopsies or excisional treatment) on histology and no evidence of HPV-16 and/or HPV-18 by type-specific HPV testing at the Week 36 visit.
Percentage of Participants with No Progression of Cervical HSIL to Cervical Carcinoma from Baseline to 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 Participants Who Have Cleared HPV-16 and/or HPV-18 in Non-cervical Anatomic Locations at Week 36 [At Week 36]
Participants will be evaluated for HPV-16 and/or HPV-18 status in specimens from non-cervical anatomic locations at the Week 36 Visit.
Change from Baseline in Levels of Serum Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations [At baseline, Week 15 and Week 36]
Levels of anti-HPV-16 and anti-HPV-18 antibody concentrations will be measured in serum samples of participants using a standardized assay at baseline, Week 15 and Week 36.
Change from Baseline in Interferon-Gamma Response Magnitude [At baseline, Week 15 and Week 36.]
Peripheral blood mononuclear cells (PBMCs) will be isolated from whole blood samples collected at baseline, Week 15 and Week 36. Assessment of cellular immune activity will be performed.
Change from Baseline in Flow Cytometry Response Magnitude [At baseline, Week 15]
Assessment of cellular immune activity will be performed using flow cytometry.

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	Mesa Obstetricians and Gynecologist	Mesa	Arizona	United States	85209
2	Women's Health Research	Scottsdale	Arizona	United States	85251
3	Visions Clinical Research-Tucson	Tucson	Arizona	United States	85712
4	Women's Medical Research Group	Clearwater	Florida	United States	33759
5	Altus Research	Lake Worth	Florida	United States	33461
6	Salom and Tangir LLC	Miramar	Florida	United States	33461
7	Comprehensive Clinical Trials LLC	West Palm Beach	Florida	United States	33409
8	Augusta University	Augusta	Georgia	United States	30912
9	Praetorian Pharmaceutical Research, LLC	Marrero	Louisiana	United States	70072
10	Saginaw Valley Medical Research Group LLC	Saginaw	Michigan	United States	48604
11	Meridian Clinical Research Norfolk	Norfolk	Nebraska	United States	68701
12	New Jersey Medical School	Newark	New Jersey	United States	07103
13	Columbia University Medical Center	New York	New York	United States	10032
14	Suffolk Obstetrics and Gynecology	Port Jefferson	New York	United States	11777
15	Lyndhurst Clinical Research	Winston-Salem	North Carolina	United States	27103
16	Greenville Pharmaceutical Research, Inc.	Greenville	South Carolina	United States	29615
17	Magnolia Ob/Gyn Research Center, LLC	Myrtle Beach	South Carolina	United States	29572
18	Chattanooga Medical Research Inc	Chattanooga	Tennessee	United States	37404
19	Women's Physician Group	Memphis	Tennessee	United States	38104
20	UAG Innovation Women Research, LLC	Houston	Texas	United States	77074
21	Group For Women	Norfolk	Virginia	United States	23502
22	Eastern Virginia Medical School	Norfolk	Virginia	United States	23507
23	Instituto de Ginecología	Rosario	Santa Fe	Argentina	S2000PBB
24	Hospital Italiano de Buenos Aires	Ciudad Autonoma de Buenos Aires		Argentina	C1181ACH
25	DIM Clínica Privada	Ramos Mejía		Argentina	B1704ETD
26	Centre Hospitalier Universitaire Ambroise Paré	Mons	Hainaut	Belgium	7000
27	Ziekenhuis Oost-Limburg	Genk	Limburg	Belgium	3600
28	Pärnu Hospital	Pärnu	Pärnumaa	Estonia	EE-80010
29	East Tallinn Central Hospital Womens Clinic	Tallin		Estonia	10119
30	Tartu University Hospital	Tartu		Estonia	51014
31	Kätilöopiston sairaala	Helsinki		Finland	290
32	Lääkäriasema Cantti Oy	Kuopio		Finland	FI-70110
33	Elisabeth Krankenhaus Essen GmbH	Essen		Germany	45138
34	Universitätsklinikum Hamburg Eppendorf	Hamburg		Germany	20246
35	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio	Italy	00168
36	Istituto Nazionale Dei Tumori	Milano		Italy	20133
37	Istituto Europeo Di Oncologia	Milan		Italy	20141
38	Vilnius University Hospital Santaros Klinikos	Vilnius		Lithuania	LT- 08661
39	Vilnius District Central Outpatient Clinic	Vilnius		Lithuania	LT-01117
40	Nuevo Hospital Civil de Guadalajara Dr. Juan I. Menchaca	Guadalajara	Jalisco	Mexico	44340
41	Unidad de Ensayos Clinicos (UNIDEC) del Policlinico Universidad Nacional Mayor de San Marcos	Lima		Peru	15083
42	Liga Peruana De Lucha Contra El Cancer	Lima		Peru	15084
43	Perpetual Succour Hospital	Cebu		Philippines	6000
44	Niepubliczny Zakład Opieki Zdrowotnej Profimed	Lublin	Lubelskie	Poland	20-880
45	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin	Lubelskie	Poland	20-880
46	Centrum Medyczne Angelius Provita	Katowice		Poland	40-611
47	Centro Hospitalar E Universitário de Coimbra EPE	Coimbra		Portugal	3000-075
48	Centro Hospitalar de Lisboa Norte, EPE - Hospital de Santa Maria	Lisboa		Portugal	1649-035
49	Puerto Rico Translational Research Center (PRTRC)	Rio Piedras		Puerto Rico	00935
50	MCM GYNPED, s.r.o.	Dubnica Nad Váhom		Slovakia	018 41
51	Univerzitna nemocnica Martin	Martin		Slovakia	036 59
52	Lynette Reynders Private Practice	Centurion	Gauteng	South Africa	157
53	University of Cape Town	Cape Town		South Africa	7925
54	Hospital Universitario de Bellvitge	Hospitalet de Llobregat	Barcelona	Spain	8907
55	Hospital Clinico San Carlos	Madrid		Spain	28040
56	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
57	Chulalongkorn University	Bangkok		Thailand	10700
58	Siriraj Hospital Mahidol University	Bangkok		Thailand	10700
59	Aberdeen Royal Infirmary - PPDS	Aberdeen		United Kingdom	AB25 7ZD
60	St Marys Hospital	London		United Kingdom	W2 1NY