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

Phase 1
Conditions
Human Papillomavirus-Related Malignant Neoplasm
Interventions
Biological: T512
Registration Number
NCT03226470
Lead Sponsor
Huazhong University of Science and Technology
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Female
Target Recruitment
40
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
T512 groupT512Subjects will receive suppository with T512 at 2 intervals for one month.
Primary Outcome Measures
NameTimeMethod
Safety-Number of participants with Adverse Events6 months

Number of participants who report adverse events as a measure of safety

Secondary Outcome Measures
NameTimeMethod
Number of dysplastic cells mearsured by ThinPrep Pap TestBaseline, 3 and 6 months

From high-grade squamous intraepithelial lesion (HSIL) to Low-grade Squamous Intraepithelial Lesion (LSIL), or from LSIL to negative

Change of HPV16 DNA titersBaseline, 3 and 6 months

Blood samples will be taken at the indicated times

Change of cervical histological resultsBaseline and 6 months

Colposcopy Biopsy will be conducted at the baseline and month 6 on each subject

Trial Locations

Locations (1)

Tongji Hospital

🇨🇳

Wuhan, Hubei, China

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