A Phase I Open Label, Dose Escalation Clinical Trial Assessing the Safety, Tolerability, and Feasibility of pNGVL4aCRTE6E7L2 HPV DNA Vaccine Administration Via Intramuscular TriGridTM Electroporation Delivery System to Patients With HPV16-Positive High-Grade Cervical Intraepithelial Neoplasia
The primary goal of this phase I open label study is to determine the safety and tolerability of pNGVL4aCRTE6E7L2 DNA vaccine, as administered by intramuscular (IM) injection with TriGrid™ electroporation to both HIV- or HIV+ adult female subjects (≥ 19 years), with biopsy confirmed cervical intraepithelial (CIN) II or III that is human papillomavirus (HPV) 16+.
• For the HIV- patient cohort only: patients with high-grade cervical intraepithelial lesions (CIN2/3) confirmed by colposcopy and biopsy who are HIV negative
• For the HIV+ patient cohort only: patients with high-grade cervical intraepithelial lesions (CIN2/3) confirmed by colposcopy and biopsy that are HIV positive
‣ HIV-1 infection, as documented by a rapid HIV-1 test or any FDA-approved HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit and confirmed by western blot at any time prior to study entry.
⁃ Two HIV-1 RNA values ≤200 copies/mL at least 24 hours apart performed by any laboratory that has Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent may be used to document infection.
⁃ Patients must be willing to comply with effective Antiretroviral Therapy.
• Patients whose cervical cytologic samples are HPV16+ by Roche Cobas 4800, Roche Linear Array HPV Genotyping test or other FDA-approved HPV genotyping test. Co-infections with HPV types other than HPV16 are permissible for study entry.
• Age ≥19 years. Also due to Alabama law the age a person is no longer a minor needing parental consent is 19, so all participants need to be 19 or older.
• Life expectancy of greater than 4 months.
• Baseline Eastern Cooperative Oncology Group performance status of 0, 1 at the time of multi-modality treatment administration
• Participants must have normal organ and marrow function within 45 days of enrollment as defined below:
∙ Absolute neutrophil count \> 1,500/mcL Cluster of differentiation (CD) 4 cell count \> 200/mcL Platelets \> 100,000/mcL Hemoglobin \> 10.0 g/dL Total bilirubin \< 1.5 X upper institutional limit of normal (patients with diagnosed Gilbert's Syndrome will not be excluded if direct bilirubin is within normal institutional limits) aspartate aminotransferase (AST) \<1.5 X the upper institutional limit of normal Alanine transaminase (ALT) \<1.5 X the upper institutional limit of normal Creatinine ≤1.5 x upper institutional limit normal
• The effects of pNGVL4aCRTE6E7L2 DNA vaccine on the developing human fetus is unknown. For this reason, women of child-bearing potential must agree to use two forms of acceptable contraception, including one barrier method, prior to study entry and for 3 months after study completion. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.
‣ Women of childbearing potential are defined as any female who has experienced menarche and does not meet the criteria for women not of childbearing potential defined below.
⁃ Women not of childbearing potential are defined as follows:
• i. Women who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) ii. Women who have experienced total cessation of menses for at least 1 year OR who have a previous clinical follicle stimulating hormone (FSH) value \> 40 mIU/mL c. The following are acceptable forms of barrier contraception: i. Male or female condom, ii. Diaphragm, cervical/vault cap, or contraceptive sponge when used with spermicidal foam/gel/cream/suppository.
• d. The following are acceptable forms of secondary contraception, when used with a barrier method and spermicide: i. Placement of an intrauterine device (IUD) ii. Established use of oral, injected, or implanted hormonal methods of contraception
• Ability to understand and the willingness to sign a written informed consent document.
• Participant is able to adhere to the study visit schedule and other protocol requirements.