Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Atypical Squamous Cells of the Cervix

Uterine Cervical Dysplasia

Precancerous Conditions

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Cervical Intraepithelial Neoplasia

Low dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.

Intermediate dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.

High dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.

Selected dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0 and 4, and the TA-CIN protein is administered by intramuscular injection at week 8.

pNGVL4aCRTE6E7L2

TA-CIN is a single fusion protein comprised of HPV16 L2, E7 and E6 proteins linked in tandem.

TA-CIN

Wendy Wu, MS

Yung-Nien Chang, Ph.D.

Nuzhat R Siddiqui, MD

Kimberly Levinson, M.D.

Richard Roden

Phase I clinical trial to assess safety of pNGVL4aCRTE6E7L2 DNA and TA-CIN protein vaccinations, and to seek the appropriate dose of the pNGVL4aCRTE6E7L2 DNA vaccine

Primary Objectives

1. To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL.
2. To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical trial.
3. To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with persistent HPV16+ ASC-US/LSIL.

Patients with a cervical cytologic diagnosis of ASC-US or LSIL

Study of Treatment for HPV16+ ASC-US or LSIL

Phase I Clinical Trial Assessing the Safety and Feasibility of Intramuscular pNGVL4aCRTE6E7L2 and TA-CIN Administration for the Treatment of Patients With Persistent HPV16+ ASC-US or LSIL

To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL

To determine the appropriate intra-muscular injection dose of pNGVL4aCRTE6E7L2 DNA vaccine as determined by toxicity and immunogenicity for a subsequent phase II clinical trial

To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine prime, TA-CIN protein vaccine boost in patients with persistent HPV16+ ASC-US/LSIL

To evaluate the levels of circulating antibody specific for HPV-16 in the peripheral blood pre- and post-vaccination

To evaluate the levels of circulating HPV-16 E6- and E7-specific CD8+ T cells and T regulatory cells in the peripheral blood pre- and post-vaccination

To evaluate the proliferative responses of peripheral blood mononucleocytes pre- and post-vaccination in response to stimulation by HPV16 E6, E7 and L2

To evaluate the presence of high risk HPV, and specifically HPV16 in cytologic specimens pre- and post-vaccination

To evaluate changes in the cytopathology of ectocervical and endocervical specimens taken pre- and post-vaccination

Johns Hopkins University

University of Alabama at Birmingham

Professor of Medicine, Division Director Gynecology Oncology

Carcinoma

Carcinoma in Situ

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Vaccines

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

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

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

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).

Kimberly Levinson, MD

Ashish Solanki, RN

Warner K Huh, MD

Rebecca C Arend, MD, MSPH

Kimberly Levinson, MD, MPH

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+.

HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia

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

Per our NCI grant resource sharing plan, this would include all coded data sets, including laboratory analyses of immune responses, as well as, if agreed to by participant, coded human specimens.

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Treatment for HPV16+ ASC-US or LSIL	NCT03913117	ASC-US LSIL	pNGVL4aCRTE6E7L... TA-CIN	19 Years -	University of Alabama at Birmingham
HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia	NCT04131413	Human Papilloma... Cervical Intrae... Cervical Intrae...	pNGVL4aCRTE6E7L...	19 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia	NCT04131413	Human Papilloma... Cervical Intrae... Cervical Intrae...	pNGVL4aCRTE6E7L...	19 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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