A Safety and Efficacy Study of TALEN and CRISPR/Cas9 in the Treatment of HPV-related Cervical Intraepithelial NeoplasiaⅠ

June 7, 2017 updated by: Hu Zheng, First Affiliated Hospital, Sun Yat-Sen University

A Safety and Efficacy Study of Transcription Activator-like Effector Nucleases and Clustered Regularly Interspaced Short Palindromic Repeat/Cas9 in the Treatment of HPV-related Cervical Intraepithelial NeoplasiaⅠ

This is an open-label and triple cohort study of the safety and efficacy of TALEN and CRISPR/Cas9 to possibly treat HPV Persistency and human cervical intraepithelial neoplasiaⅠwithout invasion.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

HPV persistent infection is the major causal factor of cervical intraepithelial neoplasia (CIN) and cervical cancer. The important roles of E6 and E7 playing in HPV-driven carcinogenesis make them attractive targets for therapeutic interventions. Previous evidences showed that using designated TALEN and CRISPR/Cas9 as genome editing tool could produce disruption of HPV16 and HPV18 E6/E7 DNA, significantly decreasing the expression of E6/E7, inducing cell apoptosis and inhibiting cell lines growth.

This study will evaluate the safety and efficacy of TALEN-HPV E6/E7 and CRISPR/Cas9-HPV E6/E7 in treating HPV Persistency and HPV-related Cervical Intraepithelial NeoplasiaⅠ

Study Type

Interventional

Enrollment (Anticipated)

60

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 Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • The First Affiliated Hospital of Sun Yat-sen University
        • Contact:

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 trial 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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TALEN
TALEN (TALEN-HPV16 E6/E7 or TALEN-HPV18 E6/E7) plasmid in gel, administered twice one week for 4 weeks.
Biological: TALEN
TALEN gel consists of TALEN plasmid, C32-447, Poloxmer 407 and distilled water as solvent.
Other Names:
  • TALEN-HPV16 E6/E7;TALEN-HPV18 E6/E7
Experimental: CRISPR/Cas9
CRISPR/Cas9 (CRISPR/Cas9-HPV16 E6/E7T1 or CRISPR/Cas9-HPV18 E6/E7T2 ）plasmid in gel, administered twice one week for 4 weeks.
Biological: CRISPR/Cas9
CRISPR/Cas9 gel consists of CRISPR/Cas9 plasmid, C32-447, Poloxmer 407 and distilled water as solvent.
Other Names:
  • CRISPR/Cas9-HPV16 E6/E7T1;CRISPR/Cas9-HPV18 E6/ E7T2
No Intervention: Control group
Observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with Adverse Events
Time Frame: 6 months
The primary objective of this Study is to evaluate the safety of therapeutic doses and the dosing regimen of TALEN and CRISPR/Cas9 plasmid.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change of HPV16 or 18 DNA titers
Time Frame: Baseline, 3 and 6 months
Blood samples will be taken at the baseline, months 3 and 6 on each subject.
Baseline, 3 and 6 months
Change of cervical cytological results.
Time Frame: Baseline, 3 and 6 months
ThinPrep Pap Test will be conducted at the baseline, months 3 and 6 on each subject.
Baseline, 3 and 6 months
Change of cervical histological results.
Time Frame: Baseline and 6 months.
Colposcopy Biopsy will be conducted at the baseline and month 6 on each subject.
Baseline and 6 months.

Collaborators and Investigators

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

Sponsor

First Affiliated Hospital, Sun Yat-Sen University

Collaborators

Jingchu University of Technology

Investigators

  • Principal Investigator: Zheng Hu, M.D., First Affiliated Hospital, Sun Yat-Sen University

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 (Anticipated)

January 15, 2018

Primary Completion (Anticipated)

November 15, 2018

Study Completion (Anticipated)

January 15, 2019

Study Registration Dates

First Submitted

February 12, 2017

First Submitted That Met QC Criteria

February 15, 2017

First Posted (Actual)

February 20, 2017

Study Record Updates

Last Update Posted (Actual)

June 9, 2017

Last Update Submitted That Met QC Criteria

June 7, 2017

Last Verified

June 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017CRISPR/Cas9&TALEN

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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