Clinical trial NCT01304524: A Study of VGX-3100 DNA Vaccine With Electroporation in Patients With Cervical Intraepithelial Neoplasia Grade 2/3 or 3
Official title: Phase II Placebo Controlled Study of VGX-3100, (HPV16 E6/E7, HPV18 E6/E7 DNA Vaccine) Delivered IM Followed by Electroporation With CELLECTRA-5P for the Treatment of Biopsy-proven CIN 2/3 or CIN 3 With Documented HPV 16 or 18.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Intraepithelial Neoplasia
Keywords: CIN 2/3 or CIN 3
Cervical cancer
Papillomavirus
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2011-02-25
Enrollment: 167
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is randomized, placebo controlled study to determine safety and efficacy of VGX-3100 DNA Vaccine delivered by Electroporation to adult women with biopsy-proven HPV 16 or 18 associated Cervical intraepithelial neoplasia grade 2/3 or 3.


Eligibility criteria: Inclusion Criteria:

* Female subjects age 18-55 years;
* Histologically confirmed HPV-16 or HPV-18-associated CIN 2/3 or CIN 3 from tissue collected less than 10 weeks prior to Vaccination/EP #1 with no evidence of invasive cancer in any specimen;
* Colposcopy is satisfactory based on visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area; lesions in ≤ 3 cervical quadrants (4 quadrant disease where the lesion occupies less than 50% of each quadrant will be considered for inclusion);
* Healthy subjects as judged by the Investigator based on medical history, PE, and normal results for an ECG, CBC, Serum Chemistries, CPK and urinalysis done up to 4 weeks prior to enrollment and administration of study drug;
* Women of child-bearing potential agree to remain sexually abstinent, use two medically effective methods of contraception (e.g. oral contraception, barrier methods, spermicide, intrauterine device (IUD)), or have a partner who is sterile (i.e., vasectomy) through 36 weeks (9 months);
* Able and willing to comply with all study procedures and voluntarily signs informed consent form

Exclusion Criteria:

* Unsatisfactory colposcopy defined as incomplete visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area;
* Pregnancy or breastfeeding
* Immunosuppression including any concurrent condition requiring the continued use of systemic or topical steroids at or near the injection site \[deltoid, upper arm\] (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents. All other corticosteroids must be discontinued \> 4 weeks prior to Day 0 of study vaccine administration; autoimmune disorders, transplant recipients;
* History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines (e.g. Gardasil®, Cervarix®) are not excluded);
* Positive serological test for hepatitis C virus or hepatitis B virus surface antigen(HBsAg) or human immunodeficiency virus (HIV)
* Administration of any blood product within 3 months of enrollment
* Administration of any licensed vaccine within 2 weeks of enrollment( 4weeks for measles vaccine)
* Participation in a study with an investigational compound or device within 30 days of signing informed consent;
* Cardiac pre-excitation syndromes (such as Wolff-Parkinson-White);
* History of seizures (unless seizure free for 5 years);
* Tattoos, scars, or active lesions/rashes within 2 cm of the intended site of vaccination/EP or any implantable leads; or any implantable leads;
* Active drug or alcohol use or dependence that, in the opinion of the investigator,would interfere with adherence to study requirements;
* Prisoners or subjects who are compulsorily detained (involuntarily incarcerated)for treatment of either a psychiatric or physical (i.e. infections disease) illness must not be enrolled into this study;
* Any other conditions judged by the investigator that would limit the evaluation of a subject

Primary outcomes:
measure: Number of Participants with Histopathological Regression of Cervical Lesions to CIN 1 or Less as a Measure of Efficacy.
timeFrame: 36 weeks
Secondary outcomes:
measure: Number of Participants with Virologically-proven Clearance of HPV 16 or 18 in Combination with Histopathological Regression of Cervical Lesions to CIN 1 or Less as a Secondary Measure of Efficacy
timeFrame: 36 Weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Tucson
country: United States
state: Arizona
city: Colton
country: United States
state: California
city: La Mesa
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Lakewood
country: United States
state: Colorado
city: Boynton Beach
country: United States
state: Florida
city: Fort Lauderdale
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Baltimore
country: United States
state: Maryland
city: Saginaw
country: United States
state: Michigan
city: Missoula
country: United States
state: Montana
city: Bronx
country: United States
state: New York
city: Port Jefferson
country: United States
state: New York
city: Raleigh
country: United States
state: North Carolina
city: Winston-Salem
country: United States
state: North Carolina
city: Columbus
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Eugene
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Myrtle Beach
country: United States
state: South Carolina
city: Murray
country: United States
state: Utah
city: Pleasant Grove
country: United States
state: Utah
city: Sandy
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Renton
country: United States
state: Washington
city: Spokane
country: United States
state: Washington
city: Victoria
country: Australia
city: Montreal
country: Canada
state: Quebec
city: Vancouver
country: Canada
city: Tallinn
country: Estonia
city: Tartu
country: Estonia
city: Batumi
country: Georgia
city: Tbilisi
country: Georgia
city: Bangalore
country: India
state: Karnataka
city: Jaipur
country: India
state: Rajasthan
city: Kolkata
country: India
city: New Delhi
country: India
city: Pune
country: India
city: Seoul
country: Korea, Republic of
city: San Juan
country: Puerto Rico
city: Bloemfontein
country: South Africa
city: Cape Town
country: South Africa
Study officials:
affiliation: Johns Hopkins University
name: Cornelia Trimble, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lyndhurst Gynecologic Associates
name: Robert L Parker, Jr., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bhuyan PK, Dallas M, Kraynyak K, Herring T, Morrow M, Boyer J, Duff S, Kim J, Weiner DB. Durability of response to VGX-3100 treatment of HPV16/18 positive cervical HSIL. Hum Vaccin Immunother. 2021 May 4;17(5):1288-1293. doi: 10.1080/21645515.2020.1823778. Epub 2020 Nov 11.
citation: Trimble CL, Morrow MP, Kraynyak KA, Shen X, Dallas M, Yan J, Edwards L, Parker RL, Denny L, Giffear M, Brown AS, Marcozzi-Pierce K, Shah D, Slager AM, Sylvester AJ, Khan A, Broderick KE, Juba RJ, Herring TA, Boyer J, Lee J, Sardesai NY, Weiner DB, Bagarazzi ML. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015 Nov 21;386(10008):2078-2088. doi: 10.1016/S0140-6736(15)00239-1. Epub 2015 Sep 17.