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

Human Papillomavirus-Related Malignant Neoplasm Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03057912
• Other study ID #: 2017CRISPR/Cas9&TALEN
• Status: Not yet recruiting
• Phase: Phase 1
• First received: February 12, 2017
• Last updated: June 7, 2017
• Start date: January 15, 2018
• Est. completion date: January 15, 2019

Study information

• Verified date: June 2017
• Source: First Affiliated Hospital, Sun Yat-Sen University
• Contact: Zheng Hu, M.D.
• Phone: 0086+18627803527
• Email: 18627803527[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: January 15, 2019
• Est. primary completion date: November 15, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Human Papillomavirus-Related Malignant Neoplasm
• Neoplasms

Intervention

Biological:
• TALEN
TALEN gel consists of TALEN plasmid, C32-447, Poloxmer 407 and distilled water as solvent.
• CRISPR/Cas9
CRISPR/Cas9 gel consists of CRISPR/Cas9 plasmid, C32-447, Poloxmer 407 and distilled water as solvent.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (2)

Lead Sponsor	Collaborator
First Affiliated Hospital, Sun Yat-Sen University	Jingchu University of Technology

Country where clinical trial is conducted

China, 

References & Publications (2)

Hu Z, Ding W, Zhu D, Yu L, Jiang X, Wang X, Zhang C, Wang L, Ji T, Liu D, He D, Xia X, Zhu T, Wei J, Wu P, Wang C, Xi L, Gao Q, Chen G, Liu R, Li K, Li S, Wang S, Zhou J, Ma D, Wang H. TALEN-mediated targeting of HPV oncogenes ameliorates HPV-related cervical malignancy. J Clin Invest. 2015 Jan;125(1):425-36. doi: 10.1172/JCI78206. Epub 2014 Dec 15. — View Citation

Hu Z, Yu L, Zhu D, Ding W, Wang X, Zhang C, Wang L, Jiang X, Shen H, He D, Li K, Xi L, Ma D, Wang H. Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. Biomed Res Int. 2014;2014:612823. doi: 10.1155/2014/612823. Epub 2014 Jul 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with Adverse Events	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	Change of HPV16 or 18 DNA titers	Blood samples will be taken at the baseline, months 3 and 6 on each subject.	Baseline, 3 and 6 months
Secondary	Change of cervical cytological results.	ThinPrep Pap Test will be conducted at the baseline, months 3 and 6 on each subject.	Baseline, 3 and 6 months
Secondary	Change of cervical histological results.	Colposcopy Biopsy will be conducted at the baseline and month 6 on each subject.	Baseline and 6 months.