A Study of VGX-3100 DNA Vaccine With Electroporation in Patients With Cervical Intraepithelial Neoplasia Grade 2/3 or 3 (HPV-003)

• ClinicalTrials.gov Identifier: NCT01304524
• Recruitment Status: Completed
• First Posted: February 25, 2011
• Last Update Posted: September 7, 2018
• Sponsor: Inovio Pharmaceuticals
• Information provided by (Responsible Party): Inovio Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cervical Intraepithelial Neoplasia	Biological: VGX 3100; Biological: Placebo; Device: CELLECTRA™-5P	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 167 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: April 2011
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: April 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: VGX 3100	Biological: VGX 3100; 1ml of VGX-3100 delivered IM followed by electroporation at Day 0, Week 4 and Week 12.; Device: CELLECTRA™-5P; CELLECTRA™-5P is used for electroporation following IM delivery of VGX 3100 or placebo on Day 0, Week 4 and Week 12.
Placebo Comparator: Placebo	Biological: Placebo; 1ml of placebo delivered IM followed by electroporation at Day 0, Week 4 and Week 12.; Device: CELLECTRA™-5P; CELLECTRA™-5P is used for electroporation following IM delivery of VGX 3100 or placebo on Day 0, Week 4 and Week 12.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Histopathological Regression of Cervical Lesions to CIN 1 or Less as a Measure of Efficacy. [ Time Frame: 36 weeks ]
   The number of participants with histopathologically confirmed CIN2/3 or CIN 3 associated with HPV16 or HPV18 whose cervical lesions regress to CIN 1 or less at the 36 week visit.

Secondary Outcome Measures :

1. 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 [ Time Frame: 36 Weeks ]
   The number of participants with histopathologically confirmed CIN2/3 or CIN 3 associated with HPV16 or HPV18 whose cervical lesions regress to CIN 1 or less and have virologically-proven clearance of HPV16 or HPV18 at the 36 week visit.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Phoenix, Arizona, United States, 85015

Tucson, Arizona, United States, 85721

United States, California

Colton, California, United States, 92324

La Mesa, California, United States, 91942

Los Angeles, California, United States, 90036

United States, Colorado

Lakewood, Colorado, United States, 80228

United States, Florida

Boynton Beach, Florida, United States, 33472

Fort Lauderdale, Florida, United States, 33316

Sarasota, Florida, United States, 34231

United States, Maryland

Baltimore, Maryland, United States, 21205

United States, Michigan

Saginaw, Michigan, United States, 48604

United States, Montana

Missoula, Montana, United States, 59808

United States, New York

Bronx, New York, United States, 10467

Port Jefferson, New York, United States, 11777

United States, North Carolina

Raleigh, North Carolina, United States, 27607

Winston-Salem, North Carolina, United States, 27103

United States, Ohio

Columbus, Ohio, United States, 43231

United States, Oklahoma

Oklahoma City, Oklahoma, United States, 73117

United States, Oregon

Eugene, Oregon, United States, 97401

United States, Pennsylvania

Philadelphia, Pennsylvania, United States, 19122

United States, South Carolina

Myrtle Beach, South Carolina, United States, 29572

United States, Utah

Murray, Utah, United States, 84107

Pleasant Grove, Utah, United States, 84062

Sandy, Utah, United States, 84070

United States, Virginia

Richmond, Virginia, United States, 23233

United States, Washington

Renton, Washington, United States, 98055

Spokane, Washington, United States, 99207

Australia

Victoria, Australia, 3052

Canada, Quebec

Montreal, Quebec, Canada, H3A 1A1

Canada

Vancouver, Canada, V5Z-1M9

Estonia

Tallinn, Estonia

Tartu, Estonia

Georgia

Batumi, Georgia, 6400

Tbilisi, Georgia

India

Bangalore, Karnataka, India, 560017

Jaipur, Rajasthan, India, 302017

Kolkata, India

New Delhi, India

Pune, India, 411043

Korea, Republic of

Seoul, Korea, Republic of

Puerto Rico

San Juan, Puerto Rico, 00936

South Africa

Bloemfontein, South Africa, 9301

Cape Town, South Africa, 7925

Sponsors and Collaborators

Inovio Pharmaceuticals

Investigators

• Principal Investigator: Cornelia Trimble, MD; Johns Hopkins University
• Principal Investigator: Robert L Parker, Jr., MD; Lyndhurst Gynecologic Associates

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Inovio Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01304524
• Other Study ID Numbers: HPV-003
• First Posted: February 25, 2011
• Last Update Posted: September 7, 2018
• Last Verified: September 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

Keywords provided by Inovio Pharmaceuticals:

CIN 2/3 or CIN 3; Cervical cancer; Papillomavirus

Additional relevant MeSH terms:

Neoplasms; Carcinoma in Situ; Uterine Cervical Dysplasia; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Precancerous Conditions; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases