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:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

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

    NCT ID: NCT02576561

    ORG ID: VAX 02-01

    Trial Conditions

    Human Papillomavirus

    High-Grade Squamous Intraepithelial Lesions

    Trial Interventions

    Drug Synonyms Arms

    Trial 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 (regression to LSIL or less)
    as assessed either by conization, LEEP or hysterectomy at last study Visit11, Day 270 (as
    determined by the treating physician). 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

    Name Type Description Interventions
    TVGV-1 (cohort 1) Experimental Antigen + Adjuvant - 0.6 mg lyophilized PEK fusion protein + 0.6 ml* GPI- 0100 (1:1 ratio)
    GPI-0100 (cohort 1) Active Comparator Adjuvant Alone - 0 mg lyophilized PEK fusion protein. 0.6 mg lyophilized placebo cake + 0.6 ml* GPI- 0100 (1:1 ratio)
    Placebo (cohort 1) Placebo Comparator Placebo- 0 mg lyophilized PEK fusion protein. 0.6 mg lyophilized placebo cake + 0.6 ml placebo-diluent (1:1 ratio)
    TVGV-1 (cohort 2) Experimental Antigen + Adjuvant - 0.9 mg lyophilized PEK fusion protein + 0.9 ml* GPI- 0100 (1:1 ratio)
    GPI-0100 (cohort 2) Active Comparator Adjuvant Alone - 0 mg lyophilized PEK fusion protein. 0.9 mg lyophilized placebo cake + 0.9 ml* GPI- 0100 (1:1 ratio)
    Placebo (cohort 2) Placebo Comparator Placebo - 0 mg lyophilized PEK fusion protein. 0.9 mg lyophilized placebo cake + 0.9 ml placebo diluent (1:1 ratio)
    TVGV-1 (cohort 3) Experimental Antigen + Adjuvant - 1.2 mg lyophilized PEK fusion protein + 1.2 ml* GPI- 0100 (1:1 ratio)
    GPI-0100 (cohort 3) Active Comparator Adjuvant Alone - 0 mg lyophilized PEK fusion protein + 1.2 mg lyophilized placebo cake 1.2 ml* GPI- 0100 (1:1 ratio)
    Placebo (cohort 3) Placebo Comparator Placebo - 0 mg lyophilized PEK fusion protein. 1.2 mg lyophilized placebo cake + 1.2 ml placebo-diluent (1:1 ratio)

    Eligibility Criteria

    Inclusion Criteria:

    1. Female age 21 to 50 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. Positive cervical cytologic sample for HPV16 by an FDA approved test (cobas HPV
    Test)

    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

    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

    19. Excessive use of acetaminophen or other potentially hepatotoxic drugs

    Minimum Eligible Age: 21 Years

    Maximum Eligible Age: 50 Years

    Eligible Gender: Female

    Primary Outcome Measures

    Absence of histologic HSIL as assessed by conization, LEEP or hysterectomy (as determined by treating physician) at last study Visit 11, Day 270.

    Assessment of cutaneous toxicities (i.e., size, induration and time to resolution of skin reactions to vaccine).

    Secondary Outcome Measures

    Absence of HPV16 in cervical cytological specimen. Absence of cervical dysplasia 6 months and 8 months after last dose of TVGV-1.

    Assessment of clinical or laboratory findings and other safety variables.

    Trial Keywords

    human papillomavirus

    Cervical Intraepithelial Neoplasia

    Cold Knife Conization

    hysterectomy

    Loop Electrosurgical Excision Procedure

    LEEP

    HSIL

    High-Grade Squamous Intraepithelial Lesion