Study of Molecular-targeted Therapy Using Zinc Finger Nuclease in Cervical Precancerous Lesions

July 9, 2017 updated by: Ding Ma, Huazhong University of Science and Technology

Safety Study of Zinc Finger Nucleases ZFN-602 and ZFN-758 in HPV-infected Subjects

This research study is being carried out to study a new way to possibly treat human cervical intraepithelial neoplasia (CIN) without invasion.

Persistent infection with specific types of human papillomavirus (HPV, most frequently types 16 and 18) may lead to precancerous lesions(CIN). If untreated, these lesions may progress to cervical cancer within many years. In the infected cells, HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. Previous studies has demonstrated that E7 alone, but not E6, is sufficient to immortalize human keratinocytes in vitro and induce high-grade cervical dysplasia in a transgenic mouse model. These data indicated that E7 may dominate the malignant progress in HPV-infected cells.

The agents zinc finger nucleases (ZFNs), called ZFN-603 and ZFN-758, which can cleave the HPV16 and HPV18 E7 oncogene specifically. ZFN-mediated disruption of HPV16 and HPV18 E7 DNA directly decreased the expression of E7, induced type-specific apoptosis in HPV16- and HPV18-positive cells, and inhibited cell growth.

The purpose of this study is to determine whether ZFN-603 and ZFN-758 are effective in the treatment of HPV16- and HPV18-positive cervical intraepithelial neoplasia.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Laboratory studies have shown that ZFN-603 and ZFN-758 could induce significant cleavage of E7 DNA in HPV16- and HPV18-positive cells. The disruption to viral DNA directly led to downregulation of E7 expression and restoration of the tumor suppressor genes retinoblastoma 1 (RB1), resulting in apoptosis and growth inhibition of ZFN-treated HPV16- and HPV18- positive cell lines. On the basis of these laboratory results, there is the potential that this may work in humans infected with high-risk HPV (especially HPV16 and HPV18) and block the progression of CIN The new treatment to be studied will involve transfecting ZFNs into HPV-infected cervical epithelials. Cells modified by ZFN-603 and ZFN-758 will lose the ability of immortalization and progress to apoptosis.

Researchers hope that these agents will be able to block the malignant progression of CIN and reduce the incidence of cervical cancer

Study Type

Interventional

Enrollment (Anticipated)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Tongji Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Documented HPV16 or HPV18 infection.
  • Married and fertile, no fertility requirements.
  • Without administration of hormone in the last six months
  • Subjects must be meet the ethical requirements and have signed informed consent

Exclusion Criteria:

  • Pregnancy and breast feeding
  • Any bacterial vaginitis
  • Any Fungal vaginitis
  • Any sexually transmitted diseases
  • Active drug or alcohol abuse
  • Any HPV medications within the past 12 weeks
  • Allergy to active or non active ingredients in the study of drugs
  • Cardiac insufficiency
  • Liver and renal insufficiency
  • Hypertension and severe complications
  • Serious illness in past 30 days
  • Currently participating in another clinical trail or any prior gene therapy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: ZFN-603 and ZFN-758
Subjects will receive suppository with ZFN-603 or ZFN-758
Biological: ZFN-603 and ZFN-758
Each suppository contain 500 µg of ZFN-603 or ZFN-758

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety - Treatment related adverse events of ZFN-603 in HPV16-positive subjects, related adverse events of ZFN-758 in HPV18-positive subjects
Time Frame: 6 months
Number of participants who report adverse events as a measure of safety
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluate persistence of HPV16 and HPV18 as measured by HPV DNA
Time Frame: 6 months
Reduce the virus titers after using ZFN-603 and ZFN-758
6 months
Change in the number of dysplastic cells as mearsured by ThinPrep Pap Test
Time Frame: 6 months
From high-grade squamous intraepithelial lesion (HSIL) to Low-grade Squamous Intraepithelial Lesion (LSIL), or from LSIL to negative.
6 months
Number of participants with Regain health or without progress
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Huazhong University of Science and Technology

Investigators

  • Principal Investigator: Wencheng Ding, M.D., Huazhong University of Science and Technology
  • Principal Investigator: Da Zhu, M.D., Huazhong University of Science and Technology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 10, 2016

Primary Completion (ACTUAL)

June 10, 2017

Study Completion (ANTICIPATED)

July 10, 2017

Study Registration Dates

First Submitted

June 1, 2016

First Submitted That Met QC Criteria

June 9, 2016

First Posted (ESTIMATE)

June 15, 2016

Study Record Updates

Last Update Posted (ACTUAL)

July 12, 2017

Last Update Submitted That Met QC Criteria

July 9, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016ZFN-V02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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