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

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ClinicalTrials.gov Identifier: NCT03913117
Recruitment Status : Recruiting
First Posted : April 12, 2019
Last Update Posted : August 2, 2019
Sponsor:
Collaborators:
University of Alabama at Birmingham
Johns Hopkins University
Information provided by (Responsible Party):
PapiVax Biotech, Inc.

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

Condition or disease Intervention/treatment Phase
ASC-US LSIL Biological: pNGVL4aCRTE6E7L2 Biological: TA-CIN Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation study
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 18, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: pNGVL4aCRTE6E7L2 0.3mg dose
Low dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
Biological: pNGVL4aCRTE6E7L2
Naked pNGVL4aCRTE6E7L2 DNA plasmid

Experimental: pNGVL4aCRTE6E7L2 1 mg dose
Intermediate dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
Biological: pNGVL4aCRTE6E7L2
Naked pNGVL4aCRTE6E7L2 DNA plasmid

Experimental: pNGVL4aCRTE6E7L2 3 mg dose
High dose of pNGVL4aCRTE6E7L2 plasmid DNA is administered by intramuscular injection at weeks 0, 4 and 8.
Biological: pNGVL4aCRTE6E7L2
Naked pNGVL4aCRTE6E7L2 DNA plasmid

Experimental: PVX-6
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.
Biological: pNGVL4aCRTE6E7L2
Naked pNGVL4aCRTE6E7L2 DNA plasmid

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




Primary Outcome Measures :
  1. Safety and feasibility of pNGVL4aCRTE6E7L2 DNA vaccination [ Time Frame: 12 months ]
    To determine the safety and feasibility of intra-muscular administration of pNGVL4aCRTE6E7L2 DNA vaccine in patients with persistent HPV16+ ASC-US/LSIL

  2. Dose finding [ Time Frame: 12 months ]
    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. Safety and feasibility of PVX-6 vaccination [ Time Frame: 12 months ]
    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 :
  1. HPV16 antibody response [ Time Frame: 12 months ]
    To evaluate the levels of circulating antibody specific for HPV-16 in the peripheral blood pre- and post-vaccination

  2. HPV16 CD8 T cell response [ Time Frame: 12 months ]
    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

  3. HPV16 L2E7E6 T cell proliferative response [ Time Frame: 12 months ]
    To evaluate the proliferative responses of peripheral blood mononucleocytes pre- and post-vaccination in response to stimulation by HPV16 E6, E7 and L2

  4. Clearance of HPV16 [ Time Frame: 12 months ]
    To evaluate the presence of high risk HPV, and specifically HPV16 in cytologic specimens pre- and post-vaccination

  5. Cytologic clearance [ Time Frame: 12 months ]
    To evaluate changes in the cytopathology of ectocervical and endocervical specimens taken pre- and post-vaccination



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Patients with a cervical cytologic diagnosis of ASC-US or LSIL
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03913117


Contacts
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Contact: Wendy Wu, MS +886 2 8226 8451 wendy@papivax.com.tw
Contact: Yung-Nien Chang, Ph.D. 410-804-9662 changyn@papivax.com

Locations
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United States, Alabama
UAB | The University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35249
Contact: Nuzhat R Siddiqui, MD         
Sponsors and Collaborators
PapiVax Biotech, Inc.
University of Alabama at Birmingham
Johns Hopkins University

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Responsible Party: PapiVax Biotech, Inc.
ClinicalTrials.gov Identifier: NCT03913117     History of Changes
Other Study ID Numbers: BB IND 18340
First Posted: April 12, 2019    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PapiVax Biotech, Inc.:
HPV16
Additional relevant MeSH terms:
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Atypical Squamous Cells of the Cervix
Uterine Cervical Dysplasia
Precancerous Conditions
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female