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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 8
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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
干预措施: VGX-3100 (Biological)
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
干预措施: VGX-3100 (Biological)
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
干预措施: VGX-3100 (Biological)
结局指标
主要结局
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.
时间窗: Through Month 4
次要结局
- 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)