Clinical trial NCT03226470: Study of Targeted Therapy Using Transcription Activator-like Effector Nucleases in Cervical Precancerous Lesions
Official title: Safety Study of Transcription Activator-like Effector Nucleases T512 in HPV16-infected Subjects
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Human Papillomavirus-Related Malignant Neoplasm
Keywords: Transcription Activator-like Effector Nucleases
Human papillomavirus
cervical intraepithelial neoplasia
Lead sponsor: Huazhong University of Science and Technology
Sponsor class: OTHER
First posted: 2017-07-21
Enrollment: 40
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety-Number of participants with Adverse Events
timeFrame: 6 months
Secondary outcomes:
measure: Change of HPV16 DNA titers
timeFrame: Baseline, 3 and 6 months
measure: Number of dysplastic cells mearsured by ThinPrep Pap Test
timeFrame: Baseline, 3 and 6 months
measure: Change of cervical histological results
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital
state: Hubei
Study officials:
affiliation: Huazhong University of Science and Technology
name: Hui Wang, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.