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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02800369
Recruitment Status : Unknown
Verified July 2017 by Ding Ma, Huazhong University of Science and Technology.
Recruitment status was:  Active, not recruiting
First Posted : June 15, 2016
Last Update Posted : July 12, 2017
Sponsor:
Information provided by (Responsible Party):
Ding Ma, Huazhong University of Science and Technology

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Human Papillomavirus-Related Malignant Neoplasm Biological: ZFN-603 and ZFN-758 Phase 1

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety Study of Zinc Finger Nucleases ZFN-602 and ZFN-758 in HPV-infected Subjects
Actual Study Start Date : December 10, 2016
Actual Primary Completion Date : June 10, 2017
Estimated Study Completion Date : July 10, 2017

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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

  2. 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.

  3. Number of participants with Regain health or without progress [ Time Frame: 6 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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

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): NCT02800369


Locations
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China, Hubei
Tongji Hospital
Wuhan, Hubei, China, 430030
Sponsors and Collaborators
Huazhong University of Science and Technology
Investigators
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Study Director: Hui Wang, M.D. Huazhong University of Science and Technology
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:
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Responsible Party: Ding Ma, Head of Cancer Biology center, Huazhong University of Science and Technology
ClinicalTrials.gov Identifier: NCT02800369    
Other Study ID Numbers: 2016ZFN-V02
First Posted: June 15, 2016    Key Record Dates
Last Update Posted: July 12, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by Ding Ma, Huazhong University of Science and Technology:
Human papillomavirus
cervical intraepithelial neoplasia
zinc finger nuclease
Additional relevant MeSH terms:
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Neoplasms