Clinical trial NCT03913117: Study of Treatment for HPV16+ ASC-US or LSIL
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: ASC-US
LSIL
Keywords: HPV16
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
First posted: 2019-04-12
Enrollment: 30
Sex: FEMALE
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation study
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Patients with persistent (\>6 month period) ASC-US/LSIL determined by cervical cytology at study entry (ThinPrep with imaging)
2. Patients whose cytologic samples are persistent (\>6 month period) HPV16+ by Roche Cobas 4800, Roche Linear Array HPV Genotyping test or other FDA-approved HPV genotyping test at study entry. Co-infections with HPV types other than HPV16 are permissible for study entry.
3. Age ≥ 19 years
4. Baseline Eastern Cooperative Oncology Group
5. Patients must have adequate organ function at the time of enrollment as defined by the following parameters:

   * White blood cell count \> 3,000
   * Absolute lymphocyte number \> 500
   * Absolute neutrophil count \> 1,000
   * Platelets \> 90,000
   * Hemoglobulin \> 9
   * Total bilirubin \<3 X the institutional limit of normal
   * AST(SGOT)/ALT(SGPT) \<3 X the institutional limit of normal
   * Creatinine \< 2.5X the institutional limit of normal
6. Women of child-bearing potential must agree to use two forms of contraception (hormonal and barrier) prior to study entry and for 3 months after study completion.
7. Ability to understand and the willingness to sign a written informed consent document.
8. Subject is able to adhere to the study visit schedule and other protocol requirements.

Exclusion Criteria:

1. Patients with ASC-US/LSIL determined by cervical cytology at study entry that are HPV16 negative.
2. Histologic evidence of CIN2+
3. Patients with a diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids.
4. Prior vaccination with any HPV antigen (prophylactic or therapeutic).
5. Patients who are receiving any other investigational agents within 28 days prior to the first dose.
6. Patients with an uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Patients with a history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease.
8. Patients with a history of allergic reactions attributed to compounds used in agent preparation.
9. Patients who are pregnant or breast feeding.
10. Patient with active or chronic infection of HIV, HCV, or HBV.
11. Patients who have had a prior LEEP or cervical conization procedure.
12. History of prior malignancy permitted if patient has been disease free for ≥ 5 years; however individuals with completely resected basal cell or squamous cell carcinoma of the skin within this interval may be enrolled.
13. Inability to understand or unwillingness to sign an informed consent document.

Primary outcomes:
measure: Safety and feasibility of pNGVL4aCRTE6E7L2 DNA vaccination
timeFrame: 12 months
measure: Dose finding
timeFrame: 12 months
measure: Safety and feasibility of PVX-6 vaccination
timeFrame: 12 months
Secondary outcomes:
measure: HPV16 antibody response
timeFrame: 12 months
measure: HPV16 CD8 T cell response
timeFrame: 12 months
measure: HPV16 L2E7E6 T cell proliferative response
timeFrame: 12 months
measure: Clearance of HPV16
timeFrame: 12 months
measure: Cytologic clearance
timeFrame: 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB | The University of Alabama at Birmingham
state: Alabama
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
Study officials:
References: