Phase I of Human Papillomavirus (HPV) DNA Plasmid (VGX-3100) + Electroporation for CIN 2 or 3

Phase I Open Label, Dose Escalation Study to Evaluate the Safety, Tolerability and Immunogenicity of Human Papillomavirus (HPV) DNA Plasmid (VGX-3100) + Electroporation (EP) in Adult Females Post Surgical or Ablative Treatment of Grade 2 or 3 Cervical Intraepithelial Neoplasia (CIN)

DNA vaccines, which are small pieces of DNA also known as plasmids, have several advantages over traditional vaccines such as live attenuated virus and recombinant protein-based vaccines. DNA vaccines appear to be well tolerated in humans. Therefore, we have developed our DNA vaccine, VGX-3100, to include plasmids targeting E6 and E7 proteins of both HPV subtypes 16 and 18. We have chosen to deliver our candidate vaccines via electroporation (EP) using the CELLECTRA™ constant current device to deliver a small electric charge following intramuscular (IM) injection, since animal studies have shown that this delivery method increases the immune response to our DNA vaccine leading to a decrease in the size of tumors caused by HPV 16 and 18. The vaccine is proposed to be given to patients with a history of CIN 2 and 3 that have been treated by surgery. We will determine which dose the DNA vaccine will be the best tolerated and elicit the strongest immune response.

Study Overview

• Status: Completed
• Conditions: Papillomavirus Infections
• Intervention / Treatment: Biological: VGX-3100

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Gynecologic Associates
  • Pennsylvania
    • Hopwood, Pennsylvania, United States, 15445
      • Laurel Highlands, OB/GYN, P.C.
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Written informed consent in accordance with institutional guidelines;
• Female 18-45 years of age;
• Post surgical (including LEEP and conization) or ablative treatment and a diagnosis of CIN 2 or 3, while under physician care as per ASCCP guidelines (Appendix D);
• Normal ECG and normal laboratory values as judged by Grade 0-1 as per Toxicity Grading Scale for Healthy Adults (Appendix C) for CBC, CPK, SMA-12 and urinalysis evaluations done up to 30 days prior to administration of study treatment;
• Body mass index (BMI) ≤30 kg/m2;
• Women of child-bearing potential (WOCBP) agree to remain sexually abstinent, use medically effective contraception (oral contraception, barrier methods, spermicide, etc), or have a partner who is sterile (i.e., vasectomy) from enrollment to 3 months after the last injection (~6 months);
• Able and willing to comply with all study procedures.

Exclusion Criteria:

• Active infection with herpes simplex virus (HSV);
• Positive serological test for HIV virus, hepatitis C virus or Hepatitis B virus surface antigen (HBsAg);
• Pregnant or breastfeeding subjects;
• Any concurrent condition requiring the continued use of systemic or topical steroids (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents. All other corticosteroids must be discontinued > 4 weeks prior to Day 1 of treatment;;
• Administration of any blood product within 3 months of enrollment;
• Administration of any vaccine within 6 weeks of enrollment;
• Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent;
• Metal implants at the site of injection;
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.6mg of DNA/dose; Subjects will receive a 3 dose series of VGX-3100 containing 0.6mg DNA/dose administered via IM injection + electroporation at Day 0, Month 1 and Month 3	Biological: VGX-3100; DNA plasmid delivered via IM injection + electroporation using CELLECTRA device
Experimental: 2mg of DNA/dose; Subjects will receive a 3 dose series of VGX-3100 containing 2mg of DNA/dose administered via IM injection + electroporation at Day 0, Month 1 and Month 3	Biological: VGX-3100; DNA plasmid delivered via IM injection + electroporation using CELLECTRA device
Experimental: 6mg of DNA/dose; Subjects will receive a 3 dose series of VGX-3100 containing 6mg DNA/dose administered via IM injection + electroporation at Day 0, Month 1 and Month 3	Biological: VGX-3100; DNA plasmid delivered via IM injection + electroporation using CELLECTRA device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of escalating doses of VGX-3100, administered by IM injection with EP to adult female subjects post surgical or ablative treatment of grade 2 or 3 CIN.	Through Month 4

Secondary Outcome Measures

Outcome Measure	Time Frame
Humoral and cellular immune responses to VGX-3100 in blood samples obtained from study subjects after each dose of a 3-dose series of VGX-3100 containing 0.6, 2 or 6 mg of DNA/dose.	At end of study

Collaborators and Investigators

• Sponsor: Inovio Pharmaceuticals
• Investigators: Principal Investigator: Robert Parker, MD, Lyndhurst Gynecologic Associates; Principal Investigator: John Sunyecz, MD, Laurel Highlands, OB/GYN, P.C.; Principal Investigator: Javier Morales, MD, Clinical Research Puerto Rico; Principal Investigator: Christina Chu, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: May 22, 2008
• First Submitted That Met QC Criteria: May 27, 2008
• First Posted (Estimate): May 28, 2008

Study Record Updates

• Last Update Posted (Actual): September 13, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: cervical cancer; CIN 2 or 3
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Tumor Virus Infections; Papillomavirus Infections
• Other Study ID Numbers: HPV001