NCT02800369

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Dec 2016

Shorter than P25 for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 1, 2016

Completed
14 days until next milestone

First Posted

Study publicly available on registry

June 15, 2016

Completed
6 months until next milestone

Study Start

First participant enrolled

December 10, 2016

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 10, 2017

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

July 10, 2017

Completed
Last Updated

July 12, 2017

Status Verified

July 1, 2017

Enrollment Period

6 months

First QC Date

June 1, 2016

Last Update Submit

July 9, 2017

Conditions

Human Papillomavirus-Related Malignant Neoplasm

Keywords

Human papillomaviruscervical intraepithelial neoplasiazinc finger nuclease

Outcome Measures

Primary Outcomes (1)

  • Safety - Treatment related adverse events of ZFN-603 in HPV16-positive subjects, related adverse events of ZFN-758 in HPV18-positive subjects

    Number of participants who report adverse events as a measure of safety

    6 months

Secondary Outcomes (3)

  • Evaluate persistence of HPV16 and HPV18 as measured by HPV DNA

    6 months

  • Change in the number of dysplastic cells as mearsured by ThinPrep Pap Test

    6 months

  • Number of participants with Regain health or without progress

    6 months

Study Arms (1)

ZFN-603 and ZFN-758

EXPERIMENTAL

Subjects will receive suppository with ZFN-603 or ZFN-758

Biological: ZFN-603 and ZFN-758

Interventions

ZFN-603 and ZFN-758BIOLOGICAL

Each suppository contain 500 µg of ZFN-603 or ZFN-758

ZFN-603 and ZFN-758

Eligibility Criteria

Age18 Years - 50 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Tongji Hospital

Wuhan, Hubei, 430030, China

Location

Related Publications (1)

  • Ding W, Hu Z, Zhu D, Jiang X, Yu L, Wang X, Zhang C, Wang L, Ji T, Li K, He D, Xia X, Liu D, Zhou J, Ma D, Wang H. Zinc finger nucleases targeting the human papillomavirus E7 oncogene induce E7 disruption and a transformed phenotype in HPV16/18-positive cervical cancer cells. Clin Cancer Res. 2014 Dec 15;20(24):6495-503. doi: 10.1158/1078-0432.CCR-14-0250. Epub 2014 Oct 21.

    PMID: 25336692BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Condition Hierarchy (Ancestors)

Precancerous ConditionsNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

Study Officials

  • Hui Wang, M.D.

    Huazhong University of Science and Technology

    STUDY DIRECTOR

  • Wencheng Ding, M.D.

    Huazhong University of Science and Technology

    PRINCIPAL INVESTIGATOR

  • Da Zhu, M.D.

    Huazhong University of Science and Technology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of Cancer Biology center

Study Record Dates

First Submitted

June 1, 2016

First Posted

June 15, 2016

Study Start

December 10, 2016

Primary Completion

June 10, 2017

Study Completion

July 10, 2017

Last Updated

July 12, 2017

Record last verified: 2017-07

Locations

CN(1)