HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia

NCT04131413 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: J1955IRB00197468118209
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

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+.

Conditions

Human Papillomavirus Type 16; Cervical Intraepithelial Neoplasia Grade II; Cervical Intraepithelial Neoplasia, Grade III

Outcome Measures

Primary Outcomes (1)

• Number of participants experiencing dose limiting toxicities at each dosing level

  The safety and tolerability of pNGVL4aCRTE6E7L2 DNA vaccine will be determined using the number of participants experiencing dose limiting toxicities at each dosing level.

  1 week

Study Arms (3)

Vaccination Arm Level 1

OTHER

The dose escalation of pNGVL4aCRTE6E7L2 will be conducted to evaluate the safety of three escalating doses; Level 1 dose of 0.3 mg

Drug: pNGVL4aCRTE6E7L2

Vaccination Arm Level 2

OTHER

The dose escalation of pNGVL4aCRTE6E7L2 will be conducted to evaluate the safety of three escalating doses; level 2 at dose 1.0 mg

Drug: pNGVL4aCRTE6E7L2

Vaccination Arm Level 3

OTHER

The dose escalation of pNGVL4aCRTE6E7L2 will be conducted to evaluate the safety of three escalating doses; level 3 dose of 3.0 mg

Drug: pNGVL4aCRTE6E7L2

Interventions

pNGVL4aCRTE6E7L2 DRUG

The dose escalation will start from the lowest dose level of 0.3 mg. This dose cohort will consist of 3 participants and a monitoring period of one week after the final dose mandated. If there are 0 participants in the 0.3 dose level cohort that experience dose limiting toxicities (DLT), a new cohort of 3 participants will be vaccinated at the 1.0 mg dose level. If there are 0 participants in the 1.0 mg dose level that experience DLT, then a new cohort of 3 participants will be vaccinated at the 3.0 mg dose level. If there is 1 participant experiencing DLTs, an additional cohort of 3 subjects will be enrolled and treated at the current dose level. If there are 2 or more participants experiencing DLTs in the 3 or additional cohort of 3 vaccinated at the current dose level, then the next lower dose level will be determined as the Maximum Tolerated Dose (MTD).

Vaccination Arm Level 1; Vaccination Arm Level 2; Vaccination Arm Level 3

Eligibility Criteria

• Age: 19 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patients with high-grade cervical intraepithelial lesions (CIN2/3) that are HPV16 negative
• 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 investigational HPV vaccine.
• 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 requirements.
• 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 40 mm.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

RECRUITING

Johns Hopkins University

Baltimore, Maryland, 21231, United States

RECRUITING

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Kimberly Levinson, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kimberly Levinson, MD

CONTACT

4109558240; klevins1@jhmi.edu

Ashish Solanki, RN

CONTACT

410-614-6702; asolank2@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three dose level cohort study

Study Record Dates

• First Submitted: October 16, 2019
• First Posted: October 18, 2019
• Study Start: September 14, 2020
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: August 24, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Time Frame: Immediately after publication of the study
• Access Criteria: Sharing is governed by Johns Hopkins University Institutional Guidelines

Locations

US (2)