Clinical trial NCT03057912: A Safety and Efficacy Study of TALEN and CRISPR/Cas9 in the Treatment of HPV-related Cervical Intraepithelial NeoplasiaⅠ
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Human Papillomavirus-Related Malignant Neoplasm
Keywords: Cervical intraepithelial neoplasiaⅠ
TALEN
CRISPR/Cas9
Lead sponsor: First Affiliated Hospital, Sun Yat-Sen University
Sponsor class: OTHER
Collaborators: name: Jingchu University of Technology
First posted: 2017-02-20
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with Adverse Events
timeFrame: 6 months
Secondary outcomes:
measure: Change of HPV16 or 18 DNA titers
timeFrame: Baseline, 3 and 6 months
measure: Change of cervical cytological results.
timeFrame: Baseline, 3 and 6 months
measure: Change of cervical histological results.
timeFrame: Baseline and 6 months.
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangdong
Study officials:
affiliation: First Affiliated Hospital, Sun Yat-Sen University
name: Zheng Hu, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hu Z, Yu L, Zhu D, Ding W, Wang X, Zhang C, Wang L, Jiang X, Shen H, He D, Li K, Xi L, Ma D, Wang H. Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. Biomed Res Int. 2014;2014:612823. doi: 10.1155/2014/612823. Epub 2014 Jul 20.
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.