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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Human Papillomavirus-Related Malignant Neoplasm

Intervention / Treatment
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* Biological: TALEN
* Biological: CRISPR/Cas9


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| Change of cervical histological results. | Colposcopy Biopsy will be conducted at the baseline and month 6 on each subject. | Baseline and 6 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TALEN, Cervical intraepithelial neoplasiaⅠ, CRISPR/Cas9