Clinical Trials /

HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia

NCT04131413

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+.

Related Conditions:
  • Cervical Intraepithelial Neoplasia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: HPV DNA Vaccine Via Electroporation for HPV16 Positive Cervical Neoplasia
  • 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

Clinical Trial IDs

  • ORG STUDY ID: J1955
  • SECONDARY ID: IRB00197468
  • SECONDARY ID: 118209
  • NCT ID: NCT04131413

Conditions

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

Interventions

DrugSynonymsArms
pNGVL4aCRTE6E7L2Vaccination Arm

Purpose

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+.

Trial Arms

NameTypeDescriptionInterventions
Vaccination ArmOtherThe dose escalation of pNGVL4aCRTE6E7L2 will be conducted to evaluate the safety of three escalating doses; Level 1 dose of 0.3 mg, level 2 at dose 1.0 mg and level 3 dose of 3.0 mg.
  • pNGVL4aCRTE6E7L2

Eligibility Criteria

        Inclusion 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:

        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.

               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:

             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.

        Exclusion Criteria:

          -  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 HPV vaccine (Gardasil or Cervarix or 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:Female
Healthy Volunteers:Accepts Healthy Volunteers

Primary Outcome Measures

Measure:Number of participants experiencing dose limiting toxicities at each dosing level
Time Frame:1 week
Safety Issue:
Description:The safety and tolerability of pNGVL4aCRTE6E7L2 DNA vaccine will be determined using the number of participants experiencing dose limiting toxicities at each dosing level.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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