RECRUITING

HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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+.

Official Title

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

Quick Facts

Study Start:2020-09-14

Study Completion:2025-04-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04131413

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:19 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:Yes

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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: * 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. 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" defined below. 2. Women not of childbearing potential are defined as follows: * 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.	* 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. * 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 enrolled. * Inability to understand or unwillingness to sign an informed consent document.

Inclusion Criteria

Exclusion Criteria

* 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:
* 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.
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" defined below.
2. Women not of childbearing potential are defined as follows:
* 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.

* 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.
* 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 enrolled.
* Inability to understand or unwillingness to sign an informed consent document.

Contacts and Locations

Study Contact

Kimberly Levinson, MD

CONTACT

4109558240

klevins1@jhmi.edu

Ashish Solanki, RN

CONTACT

410-614-6702

asolank2@jhmi.edu

Principal Investigator

Kimberly Levinson, MD

PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35233

United States

Johns Hopkins University

Baltimore, Maryland, 21231

United States

Collaborators and Investigators

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Kimberly Levinson, MD, PRINCIPAL_INVESTIGATOR, Johns Hopkins University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-09-14

Study Completion Date2025-04-30

Study Record Updates

Study Start Date2020-09-14

Study Completion Date2025-04-30

Terms related to this study

Additional Relevant MeSH Terms

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