Study of Targeted Therapy Using Transcription Activator-like Effector Nucleases in Cervical Precancerous Lesions

Study Overview
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Brief Summary
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This is an single arm clinical study of the safety and efficacy of T512 to possibly treat cervical intraepithelial neoplasia(CIN).

Detailed Description
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Persistent infection with high-risk human papillomavirus (HPVs),especially types 16 and 18,may lead to cervical intraepithelial neoplasia(CIN).HPVs expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. Previous studies showed that using designated TALENs (T27 and T512) targeted HPV16 E6 and E7 produced disruption of HPV16 E6 and E7 DNA, decreased the expression of E6 and E7 proteins, and induced cell apoptosis. This study will evaluate the safety and efficacy of and T512 in treating HPV Persistency and HPV16-positive CIN.

Official Title
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Safety Study of Transcription Activator-like Effector Nucleases T512 in HPV16-infected Subjects

Conditions
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Human Papillomavirus-Related Malignant Neoplasm

Intervention / Treatment
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* Biological: T512


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented HPV16 infection and integration. Married and fertile, no fertility requirements. The cervical transformation zone was type I or II, and the biopsy results under colposcopy suggested SIL. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T512 group<br>Subjects will receive suppository with T512 at 2 intervals for one month. | Biological: T512<br>* T512 suppository contain 500 µg of T512 and suppocire.<br>* Other names: TALEN-T512;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety-Number of participants with Adverse Events | Number of participants who report adverse events as a measure of safety | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of HPV16 DNA titers | Blood samples will be taken at the indicated times | Baseline, 3 and 6 months | 
| Number of dysplastic cells mearsured by ThinPrep Pap Test | From high-grade squamous intraepithelial lesion (HSIL) to Low-grade Squamous Intraepithelial Lesion (LSIL), or from LSIL to negative | 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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Transcription Activator-like Effector Nucleases, Human papillomavirus, cervical intraepithelial neoplasia