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Study of Treatment for HPV16+ ASC-US or LSIL (PVX-6)

Primary Purpose

ASC-US, LSIL

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
pNGVL4aCRTE6E7L2
TA-CIN
Sponsored by
University of Alabama at Birmingham
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ASC-US focused on measuring HPV16

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • UAB | The University of Alabama at BirminghamRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

pNGVL4aCRTE6E7L2 0.3mg dose

pNGVL4aCRTE6E7L2 1 mg dose

pNGVL4aCRTE6E7L2 3 mg dose

PVX-6

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety and feasibility of pNGVL4aCRTE6E7L2 DNA vaccination
To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL
Dose finding
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
Safety and feasibility of PVX-6 vaccination
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

Secondary Outcome Measures

HPV16 antibody response
To evaluate the levels of circulating antibody specific for HPV-16 in the peripheral blood pre- and post-vaccination
HPV16 CD8 T cell response
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
HPV16 L2E7E6 T cell proliferative response
To evaluate the proliferative responses of peripheral blood mononucleocytes pre- and post-vaccination in response to stimulation by HPV16 E6, E7 and L2
Clearance of HPV16
To evaluate the presence of high risk HPV, and specifically HPV16 in cytologic specimens pre- and post-vaccination
Cytologic clearance
To evaluate changes in the cytopathology of ectocervical and endocervical specimens taken pre- and post-vaccination

Full Information

First Posted
April 10, 2019
Last Updated
July 30, 2023
Sponsor
University of Alabama at Birmingham
Collaborators
Johns Hopkins University
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1. Study Identification

Unique Protocol Identification Number
NCT03913117
Brief Title
Study of Treatment for HPV16+ ASC-US or LSIL
Acronym
PVX-6
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

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 10, 2023 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
December 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Alabama at Birmingham
Collaborators
Johns Hopkins University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ASC-US, LSIL
Keywords
HPV16

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Dose escalation study
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
pNGVL4aCRTE6E7L2 0.3mg dose
Arm Type
Experimental
Arm Description
Low dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
Arm Title
pNGVL4aCRTE6E7L2 1 mg dose
Arm Type
Experimental
Arm Description
Intermediate dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
Arm Title
pNGVL4aCRTE6E7L2 3 mg dose
Arm Type
Experimental
Arm Description
High dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
Arm Title
PVX-6
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
pNGVL4aCRTE6E7L2
Intervention Description
Naked pNGVL4aCRTE6E7L2 DNA plasmid
Intervention Type
Biological
Intervention Name(s)
TA-CIN
Intervention Description
TA-CIN is a single fusion protein comprised of HPV16 L2, E7 and E6 proteins linked in tandem.
Primary Outcome Measure Information:
Title
Safety and feasibility of pNGVL4aCRTE6E7L2 DNA vaccination
Description
To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL
Time Frame
12 months
Title
Dose finding
Description
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
Time Frame
12 months
Title
Safety and feasibility of PVX-6 vaccination
Description
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
Time Frame
12 months
Secondary Outcome Measure Information:
Title
HPV16 antibody response
Description
To evaluate the levels of circulating antibody specific for HPV-16 in the peripheral blood pre- and post-vaccination
Time Frame
12 months
Title
HPV16 CD8 T cell response
Description
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
Time Frame
12 months
Title
HPV16 L2E7E6 T cell proliferative response
Description
To evaluate the proliferative responses of peripheral blood mononucleocytes pre- and post-vaccination in response to stimulation by HPV16 E6, E7 and L2
Time Frame
12 months
Title
Clearance of HPV16
Description
To evaluate the presence of high risk HPV, and specifically HPV16 in cytologic specimens pre- and post-vaccination
Time Frame
12 months
Title
Cytologic clearance
Description
To evaluate changes in the cytopathology of ectocervical and endocervical specimens taken pre- and post-vaccination
Time Frame
12 months

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Patients with a cervical cytologic diagnosis of ASC-US or LSIL
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with persistent (>6 month period) ASC-US/LSIL determined by cervical cytology at study entry (ThinPrep with imaging) 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. Age ≥ 19 years Baseline Eastern Cooperative Oncology Group 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 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. Ability to understand and the willingness to sign a written informed consent document. Subject is able to adhere to the study visit schedule and other protocol requirements. Exclusion Criteria: Patients with ASC-US/LSIL determined by cervical cytology at study entry that are HPV16 negative. Histologic evidence of CIN2+ Patients with a diagnosis of immunosuppression or prolonged, active use of immunosuppressive medications such as steroids. Prior vaccination with any HPV antigen (prophylactic or therapeutic). Patients who are receiving any other investigational agents within 28 days prior to the first dose. 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. Patients with a history of autoimmune disease such as multiple sclerosis, exclusive of a history of thyroiditis, psoriasis, Sjrogen's, or inflammatory bowel disease. Patients with a history of allergic reactions attributed to compounds used in agent preparation. Patients who are pregnant or breast feeding. Patient with active or chronic infection of HIV, HCV, or HBV. Patients who have had a prior LEEP or cervical conization procedure. 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. Inability to understand or unwillingness to sign an informed consent document.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wendy Wu, MS
Phone
+886 2 8226 8451
Email
wendy@papivax.com.tw
First Name & Middle Initial & Last Name or Official Title & Degree
Yung-Nien Chang, Ph.D.
Phone
410-804-9662
Email
changyn@papivax.com
Facility Information:
Facility Name
UAB | The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nuzhat R Siddiqui, MD

12. IPD Sharing Statement

Learn more about this trial

Study of Treatment for HPV16+ ASC-US or LSIL

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