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

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ClinicalTrials.gov Identifier: NCT02576561
Recruitment Status : Unknown
Verified October 2017 by THEVAX Genetics Vaccine.
Recruitment status was:  Active, not recruiting
First Posted : October 15, 2015
Last Update Posted : October 25, 2017
Sponsor:
Collaborator:
Clinical Research Management, Inc.
Information provided by (Responsible Party):
THEVAX Genetics Vaccine

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Human Papillomavirus High-Grade Squamous Intraepithelial Lesions Biological: TVGV-1 Biological: GPI-0100 Biological: Placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
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
Study Start Date : November 2015
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : September 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TVGV-1 (cohort 1)
Antigen + Adjuvant - 0.6 mg lyophilized PEK fusion protein + 0.6 ml* GPI- 0100 (1:1 ratio)
Biological: TVGV-1
Antigen + Adjuvant
Other Names:
  • lyophilized PEK fusion protein
  • GPI-0100
  • Antigen
  • Adjuvant

Active Comparator: GPI-0100 (cohort 1)
Adjuvant Alone - 0 mg lyophilized PEK fusion protein. 0.6 mg lyophilized placebo cake + 0.6 ml* GPI- 0100 (1:1 ratio)
Biological: GPI-0100
Adjuvant Alone
Other Name: Adjuvant

Placebo Comparator: Placebo (cohort 1)
Placebo- 0 mg lyophilized PEK fusion protein. 0.6 mg lyophilized placebo cake + 0.6 ml placebo-diluent (1:1 ratio)
Biological: Placebo
Placebo
Other Names:
  • lyophilized placebo cak
  • placebo diluent
  • sterile water

Experimental: TVGV-1 (cohort 2)
Antigen + Adjuvant - 0.9 mg lyophilized PEK fusion protein + 0.9 ml* GPI- 0100 (1:1 ratio)
Biological: TVGV-1
Antigen + Adjuvant
Other Names:
  • lyophilized PEK fusion protein
  • GPI-0100
  • Antigen
  • Adjuvant

Active Comparator: GPI-0100 (cohort 2)
Adjuvant Alone - 0 mg lyophilized PEK fusion protein. 0.9 mg lyophilized placebo cake + 0.9 ml* GPI- 0100 (1:1 ratio)
Biological: GPI-0100
Adjuvant Alone
Other Name: Adjuvant

Placebo Comparator: Placebo (cohort 2)
Placebo - 0 mg lyophilized PEK fusion protein. 0.9 mg lyophilized placebo cake + 0.9 ml placebo diluent (1:1 ratio)
Biological: Placebo
Placebo
Other Names:
  • lyophilized placebo cak
  • placebo diluent
  • sterile water

Experimental: TVGV-1 (cohort 3)
Antigen + Adjuvant - 1.2 mg lyophilized PEK fusion protein + 1.2 ml* GPI- 0100 (1:1 ratio)
Biological: TVGV-1
Antigen + Adjuvant
Other Names:
  • lyophilized PEK fusion protein
  • GPI-0100
  • Antigen
  • Adjuvant

Active Comparator: GPI-0100 (cohort 3)
Adjuvant Alone - 0 mg lyophilized PEK fusion protein + 1.2 mg lyophilized placebo cake 1.2 ml* GPI- 0100 (1:1 ratio)
Biological: GPI-0100
Adjuvant Alone
Other Name: Adjuvant

Placebo Comparator: Placebo (cohort 3)
Placebo - 0 mg lyophilized PEK fusion protein. 1.2 mg lyophilized placebo cake + 1.2 ml placebo-diluent (1:1 ratio)
Biological: Placebo
Placebo
Other Names:
  • lyophilized placebo cak
  • placebo diluent
  • sterile water




Primary Outcome Measures :
  1. Absence of histologic HSIL (CIN2/3) as assessed by biopsy at last study Visit 11, Day 270. [ Time Frame: DAY 270 ]
    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.

  2. Assessment of cutaneous toxicities (i.e., size, induration and time to resolution of skin reactions to vaccine). [ Time Frame: DAY 270 ]
    Summaries of the data pertaining to the primary safety outcome of skin toxicity will be provided. Summaries will be provided for the within-cohort subsets of subjects treated with the active, and with the adjuvant alone; and the combined subsets across all three cohorts of subject treated with the active, with the adjuvant alone, and with the placebo. Serious adverse events will be described in narrative with the participant's demographics, treatment date, event, onset date, relationship to the study treatment and the descriptions of the actions and outcomes during this event. Any deaths occurring in the study will be summarized in narrative with the demographics, treatment duration, cause of death, date of death and additional information surrounding that serious adverse event.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Assessment of clinical or laboratory findings and other safety variables. [ Time Frame: DAy 270 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

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): NCT02576561


Locations
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United States, Arizona
Visions Clinical Research - Tucson
Tucson, Arizona, United States, 85712
United States, Colorado
Red Rocks OBGYN
Lakewood, Colorado, United States, 80228
United States, Florida
Progressive Medical Research
Port Orange, Florida, United States, 32127
Comprehensive Clinical Trials, LLC
West Palm Beach, Florida, United States, 33409
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
United States, New York
ProHEALTH Care Associates LLP
Port Jefferson, New York, United States, 11777
United States, North Carolina
Unified Women's Clinical Research
Raleigh, North Carolina, United States, 27607
Unified Women's Clinical Research
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Complete Healthcare for Women
Columbus, Ohio, United States, 43231
United States, Pennsylvania
Penn Fertility Care/Reproductive Research Unit Univ of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
Insearch-Tidewater Clinical Research
Norfolk, Virginia, United States, 23502
Sponsors and Collaborators
THEVAX Genetics Vaccine
Clinical Research Management, Inc.
Investigators
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Study Director: Frank L Douglas, PhD, MD THEVAX Genetics Vaccine

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Responsible Party: THEVAX Genetics Vaccine
ClinicalTrials.gov Identifier: NCT02576561     History of Changes
Other Study ID Numbers: VAX 02-01
First Posted: October 15, 2015    Key Record Dates
Last Update Posted: October 25, 2017
Last Verified: October 2017
Keywords provided by THEVAX Genetics Vaccine:
human papillomavirus
Cervical Intraepithelial Neoplasia
Cold Knife Conization
hysterectomy
Loop Electrosurgical Excision Procedure
LEEP
HSIL
High-Grade Squamous Intraepithelial Lesion
Additional relevant MeSH terms:
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Squamous Intraepithelial Lesions of the Cervix
Uterine Cervical Dysplasia
Precancerous Conditions
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Vaccines
Immunologic Factors
Physiological Effects of Drugs