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

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ClinicalTrials.gov Identifier: NCT03057912
Recruitment Status : Not yet recruiting
First Posted : February 20, 2017
Last Update Posted : June 9, 2017
Sponsor:
Collaborator:
Jingchu University of Technology
Information provided by (Responsible Party):
Hu Zheng, First Affiliated Hospital, Sun Yat-Sen University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Human Papillomavirus-Related Malignant Neoplasm Biological: TALEN Biological: CRISPR/Cas9 Phase 1

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  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: open label
Primary Purpose: Treatment
Official Title: 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
Estimated Study Start Date : January 15, 2018
Estimated Primary Completion Date : November 15, 2018
Estimated Study Completion Date : January 15, 2019

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 Name: 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 Name: CRISPR/Cas9-HPV16 E6/E7T1;CRISPR/Cas9-HPV18 E6/ E7T2

No Intervention: Control group
Observation



Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



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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 trial 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): NCT03057912


Contacts
Contact: Zheng Hu, M.D. 0086+18627803527 18627803527@163.com

Locations
China, Guangdong
The First Affiliated Hospital of Sun Yat-sen University Not yet recruiting
Guangzhou, Guangdong, China, 510080
Contact: Zheng Hu, M.D.    0086+18627803527    18627803527@163.com   
Sponsors and Collaborators
First Affiliated Hospital, Sun Yat-Sen University
Jingchu University of Technology
Investigators
Principal Investigator: Zheng Hu, M.D. First Affiliated Hospital, Sun Yat-Sen University

Publications:
Responsible Party: Hu Zheng, Principal Investigator, First Affiliated Hospital, Sun Yat-Sen University
ClinicalTrials.gov Identifier: NCT03057912     History of Changes
Other Study ID Numbers: 2017CRISPR/Cas9&TALEN
First Posted: February 20, 2017    Key Record Dates
Last Update Posted: June 9, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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

Keywords provided by Hu Zheng, First Affiliated Hospital, Sun Yat-Sen University:
Cervical intraepithelial neoplasiaⅠ
TALEN
CRISPR/Cas9

Additional relevant MeSH terms:
Neoplasms