Clinical trial NCT00685412: Phase I of Human Papillomavirus (HPV) DNA Plasmid (VGX-3100) + Electroporation for CIN 2 or 3
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Papillomavirus Infections
Keywords: CIN 2 or 3
cervical cancer
Lead sponsor: Inovio Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-05-28
Enrollment: 18
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Through Month 4
Secondary outcomes:
measure: 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.
timeFrame: At end of study
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Lyndhurst Gynecologic Associates
state: North Carolina
city: Hopwood
country: United States
facility: Laurel Highlands, OB/GYN, P.C.
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
Study officials:
affiliation: University of Pennsylvania
name: Christina Chu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lyndhurst Gynecologic Associates
name: Robert Parker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Laurel Highlands, OB/GYN, P.C.
name: John Sunyecz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinical Research Puerto Rico
name: Javier Morales, MD
role: PRINCIPAL_INVESTIGATOR
References: