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

Phase 1

• Conditions: Human Papillomavirus-Related Malignant Neoplasm
• Interventions: Biological: TALEN; Biological: CRISPR/Cas9

• Registration Number: NCT03057912
• Lead Sponsor: 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.

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 Timeline

• Study First Submitted: 2017-02-12
• Study First Submitted QC: 2017-02-15
• Study First Posted: 2017-02-20
• Status Verified: 2017-06
• Last Update Submitted: 2017-06-07
• Last Update Posted: 2017-06-09
• Study Start: 2018-01-15
• Primary Completion: 2018-11-15
• Study Completion: 2019-01-15

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TALEN	TALEN	TALEN (TALEN-HPV16 E6/E7 or TALEN-HPV18 E6/E7) plasmid in gel, administered twice one week for 4 weeks.
CRISPR/Cas9	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.

Primary Outcome Measures

Name	Time	Method
Number of participants with Adverse Events	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

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

Trial Locations

Locations (1)

The First Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China