Clinical Trials /

Safety and Efficacy Study of TVGV-1 Vaccine to Treat HPV Induced Cervical HSIL

NCT02576561

Description:

The purpose of this research study is to test the safety and effectiveness of the investigational study vaccine, called TVGV-1. The study will test the vaccine in women with high grade HPV cervical infection.

Related Conditions:
  • High Grade Cervical Intraepithelial Neoplasia
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study of TVGV-1 Vaccine to Treat HPV Induced Cervical HSIL
  • Official Title: Phase 2a Double-Blind, Randomized, Parallel Group, Dose-Ranging Study to Assess the Safety and Efficacy of Three Doses of TVGV-1 Vaccine Compared to Its Adjuvant, GPI-0100, in Subjects With Histologically Confirmed HPV Induced Cervical HSIL

Clinical Trial IDs

  • ORG STUDY ID: VAX 02-01
  • NCT ID: NCT02576561

Conditions

  • Human Papillomavirus
  • High-Grade Squamous Intraepithelial Lesions

Interventions

DrugSynonymsArms
TVGV-1lyophilized PEK fusion protein, GPI-0100, Antigen, AdjuvantTVGV-1 (cohort 1)
GPI-0100AdjuvantGPI-0100 (cohort 1)
Placebolyophilized placebo cak, placebo diluent, sterile waterPlacebo (cohort 1)

Purpose

The purpose of this research study is to test the safety and effectiveness of the investigational study vaccine, called TVGV-1. The study will test the vaccine in women with high grade HPV cervical infection.

Detailed Description

      The purpose of the Phase 2a Study VAX 02-01 is to assess the safety and activity of TVGV-1
      vaccine construct in achieving the absence of histologic HSIL (CIN2/3) (regression to LSIL or
      less) as assessed by biopsy at last study Visit 11, Day 270.

      The objective of the TVGV-1 program is to develop a non-surgical alternative that is
      reliable, safe, and would avoid potential surgical risks such as preterm birth, perinatal
      mortality, risk of infertility, incontinence and disfigurement, as well as reduced cost and
      inconvenience for an otherwise economically productive young subject population.
    

Trial Arms

NameTypeDescriptionInterventions
TVGV-1 (cohort 1)ExperimentalAntigen + Adjuvant - 0.6 mg lyophilized PEK fusion protein + 0.6 ml* GPI- 0100 (1:1 ratio)
  • TVGV-1
GPI-0100 (cohort 1)Active ComparatorAdjuvant Alone - 0 mg lyophilized PEK fusion protein. 0.6 mg lyophilized placebo cake + 0.6 ml* GPI- 0100 (1:1 ratio)
  • GPI-0100
Placebo (cohort 1)Placebo ComparatorPlacebo- 0 mg lyophilized PEK fusion protein. 0.6 mg lyophilized placebo cake + 0.6 ml placebo-diluent (1:1 ratio)
  • Placebo
TVGV-1 (cohort 2)ExperimentalAntigen + Adjuvant - 0.9 mg lyophilized PEK fusion protein + 0.9 ml* GPI- 0100 (1:1 ratio)
  • TVGV-1
GPI-0100 (cohort 2)Active ComparatorAdjuvant Alone - 0 mg lyophilized PEK fusion protein. 0.9 mg lyophilized placebo cake + 0.9 ml* GPI- 0100 (1:1 ratio)
  • GPI-0100
Placebo (cohort 2)Placebo ComparatorPlacebo - 0 mg lyophilized PEK fusion protein. 0.9 mg lyophilized placebo cake + 0.9 ml placebo diluent (1:1 ratio)
  • Placebo
TVGV-1 (cohort 3)ExperimentalAntigen + Adjuvant - 1.2 mg lyophilized PEK fusion protein + 1.2 ml* GPI- 0100 (1:1 ratio)
  • TVGV-1
GPI-0100 (cohort 3)Active ComparatorAdjuvant Alone - 0 mg lyophilized PEK fusion protein + 1.2 mg lyophilized placebo cake 1.2 ml* GPI- 0100 (1:1 ratio)
  • GPI-0100
Placebo (cohort 3)Placebo ComparatorPlacebo - 0 mg lyophilized PEK fusion protein. 1.2 mg lyophilized placebo cake + 1.2 ml placebo-diluent (1:1 ratio)
  • Placebo

Eligibility Criteria

        Inclusion Criteria:

          1. Female age 18 to 55 years

          2. Written informed consent in accordance with institutional guidelines

          3. Negative pregnancy test (urine and blood tests)

          4. Women of child bearing potential must agree to use contraception through one menstrual
             cycle post end of study or if early withdrawal, through what would have been visit 11.
             Methods include intrauterine device or double barrier method, hormonal contraceptive
             in combination with a double barrier method.

          5. Patients who have ONLY HPV 16 OR HPV 16 AND 18 and no other High-Risk HPV by Cobas
             test will be included.

          6. Histologically confirmed, positive HSIL of CIN2+ or higher (only CIN2+/3 subjects will
             be selected) cervical biopsy, confirmed by external (independent) pathologist panel
             within the 12 weeks prior to enrollment. If the standard care biopsy is not available
             for evaluation by the independent pathologist, a fresh biopsy and endocervical
             curettage will be required. The extent of colposcopic HSIL disease should not involve
             more than two quadrants of the cervix. Biopsies should be taken from each affected
             quadrant

          7. Adequate visualization of entire cervix, cervical lesion(s) and squamous-columnar
             junction

          8. Normal electrocardiogram (ECG), laboratory values (chemistry, complete blood count)
             and urinalysis, as judged Grade 0-1 by per National Cancer Institute Common Toxicity
             Criteria (NCI-CTC)

          9. Agrees to Loop Electrosurgical Excision Procedure (LEEP), Cold Knife Conization (CKC)
             or Hysterectomy being performed at the end of study according to the standard-of-care

        Exclusion Criteria:

          1. History of cancer (excluding basal cell carcinoma of the skin) including cervical
             cancer

          2. Eastern Cooperative Oncology Group (ECOG) performance status >2 (See Appendix G)

          3. Administration of any blood product within 3 months of enrollment

          4. Active infection requiring antimicrobial treatment that would interfere with
             interpretation of adverse events, cutaneous reactions or efficacy. Treatment of minor
             concurrent infections should be limited to less than 10 days.

          5. Administration of any vaccine within 8 weeks of enrollment and within 4 weeks for flu
             vaccine.

          6. Participation in any study with an investigational compound or device within 30 days
             prior to signing informed consent

          7. Any hematologic disorder involving platelets or clotting abnormalities or any
             condition requiring treatment with transfusions, anticoagulants except platelet
             inhibitors (NSAIDs as needed for pain are permitted)

          8. Active drug or alcohol use or dependence that, in the opinion of the Site
             Investigator, would interfere with adherence to study protocol

          9. Skin conditions that require consistent use of topical corticosteroids or other local
             or systemic therapy that may interfere with interpretation or description of
             skin-related adverse events linked to vaccination

         10. The standard criteria for prospective clinical trials of medications developed by
             Drug-Induced Liver Injury Network (established by The National Institute of Diabetes
             and Digestive and Kidney Diseases) will be used to assess the laboratory test
             abnormalities. Normal range for these labs will typically be 5 - 40 IU/L for AST; 7 -
             56 IU/L for ALT; 0.2 - 1.2 mg/dL for bilirubin. Subjects will be excluded if values
             are x 2-x 2.5 the upper limit

         11. Evidence of hematopoietic, cardiovascular, hepatic, renal, neurologic, psychiatric,
             dermatologic, immune disorder, or other disease that may interfere with assessment of
             safety or efficacy of vaccine activity as indicated in study objectives

         12. Any known allergic reaction to vaccine components

         13. Any other medical condition(s) that, in the judgment of the Site Investigator, might
             interfere with the study or require treatment that might interfere with the study

         14. Family member of the investigation study staff

         15. Pregnant or breast-feeding

         16. Inability to provide informed consent

         17. A subject with a history or expectation of noncompliance with medications or treatment
             protocol

         18. Receipt of (e.g. Gardasil® or Cervarix®) HPV preventative vaccines within 8 years of
             study enrollment

         19. Excessive use of acetaminophen or other potentially hepatotoxic drugs
      
Maximum Eligible Age:55 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Absence of histologic HSIL (CIN2/3) as assessed by biopsy at last study Visit 11, Day 270.
Time Frame:DAY 270
Safety Issue:
Description:The primary analysis for efficacy will be a comparison between subjects treated with and without the PEK fusion protein with respect to the percentage who present regression of HSIL at Day 270. Separate comparisons within each cohort will be performed using Fisher's exact test (or an appropriate analogue). No adjustment for multiple comparisons will be employed in these analyses. Additionally, a corresponding comparison across all study subjects combined will be performed, based on Cochran-Matel-Haenszel test stratified for cohort.

Secondary Outcome Measures

Measure:Absence of HPV16 in cervical cytological specimen. Absence of cervical dysplasia 6 months and 8 months after last dose of TVGV-1.
Time Frame:DAY 270
Safety Issue:
Description:The primary analysis for efficacy will be a comparison between subjects treated with and without the PEK fusion protein with respect to the percentage who present regression of HSIL at Day 270. Separate comparisons within each cohort will be performed using Fisher's exact test (or an appropriate analogue). No adjustment for multiple comparisons will be employed in these analyses. Additionally, a corresponding comparison across all study subjects combined will be performed, based on Cochran-Matel-Haenszel test stratified for cohort.
Measure:Assessment of clinical or laboratory findings and other safety variables.
Time Frame:DAy 270
Safety Issue:
Description:Appropriate laboratory data will be transformed prior to analysis as defined in the Statistical Analysis Plan (SAP). Summaries will be presented for each evaluation time point, as well as for changes from baseline. Changes from baseline will also be presented using shift tables for selected laboratory parameters.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:THEVAX Genetics Vaccine

Trial Keywords

  • human papillomavirus
  • Cervical Intraepithelial Neoplasia
  • Cold Knife Conization
  • hysterectomy
  • Loop Electrosurgical Excision Procedure
  • LEEP
  • HSIL
  • High-Grade Squamous Intraepithelial Lesion

Last Updated

October 25, 2017