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
1. 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.
2. 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.
3. 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
- 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
1. 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"
2. 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
- Patients with high-grade cervical intraepithelial lesions (CIN2/3) that are HPV16
- For the HIV+ cohort only: patients with AIDS related symptoms comprising an active
AIDS-associated infectious process that, in the view of the investigator, would limit
the subject's ability to comply with study procedures.
- For the HIV+ cohort only: patients with an HIV viral load >200 cp/mL.
- Administration of chronic (defined as more than 14 days) immunosuppressants or other
immune-modifying drugs within 6 months of study entry; For corticosteroids, this will
mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day; inhaled and
topical steroids are allowed.
- Due to interference with the immunologic measurements and compromising the analysis of
the safety of the vaccine, participants with active or chronic infection of hepatitis
C virus (HCV) or hepatitis B virus (HBV) are excluded as well as those who have
previously received an HPV vaccine (Gardasil or Cervarix or an investigational HPV
- Participants who are receiving or have received any other investigational agents
within 30 days of registration.
- Participants with an uncontrolled intercurrent illness including, but not limited to,
ongoing or active systemic infection (yeast, bacterial, or viral), symptomatic
congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or
psychiatric illness/social situations that would limit compliance with study
- Participants with a history of autoimmune disease such as systemic lupus
erythematosus, celiac disease, autoimmune hepatitis, multiple sclerosis, exclusive of
a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.
- Pregnant and breastfeeding women are excluded from this study because pNGVL4aCRTE6E7L2
is a vaccine with unknown potential for teratogenic or abortifacient effects.
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to pNGVL4aCRTE6E7L2 DNA vaccine.
- Participants with a metal implant(s) at the site of injection or any electronic
stimulation device, such as cardiac demand pacemakers, automatic implantable cardiac
defibrillator, nerve stimulators, or deep brain stimulators.
- Any chronic or active neurologic disorder, including seizures and epilepsy, excluding
a single febrile seizure as a child.
- Syncopal episode within 12 months of screening.
- Administration of immunoglobulins and/or any blood products within the 120 days
preceding study entry or planned administration during the study period
- Individuals in which a skin-fold measurement of the cutaneous and subcutaneous tissue
for all eligible injection sites (deltoid muscles with intact lymph drainage) exceeds
- Individuals in whom the ability to observe possible local reactions at the eligible
injection sites (deltoid region) is, in the opinion of the investigator, unacceptably
obscured due to a physical condition or permanent body art.
- Acute or chronic, clinically significant hematologic, pulmonary, cardiovascular, or
hepatic or renal functional abnormality as determined by the investigator based on
medical history, physical examination, previous EKG, and/or laboratory screening test.
- History of prior malignancy < 5 years; however individuals with completely resected
basal cell or squamous cell carcinoma of the skin within this interval may be
- Inability to understand or unwillingness to sign an informed consent document.