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

Human Papillomavirus-Related Malignant Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03226470
• Other study ID #: 2017TALEN-V02
• Status: Recruiting
• Phase: Phase 1
• Start date: March 10, 2017
• Est. completion date: June 10, 2022

Study information

• Verified date: December 2021
• Source: Huazhong University of Science and Technology
• Contact: Ding Ma, M.D.
• Phone: 86-27-83662681
• Email: dma[@]tjh.tjmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: June 10, 2022
• Est. primary completion date: February 10, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Human Papillomavirus-Related Malignant Neoplasm
• Neoplasms

Intervention

Biological:
• T512
T512 suppository contain 500 µg of T512 and suppocire.

Locations

Country	Name	City	State
China	Tongji Hospital	Wuhan	Hubei

Sponsors (1)

Lead Sponsor	Collaborator
Huazhong University of Science and Technology

Country where clinical trial is conducted

China, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety-Number of participants with Adverse Events	Number of participants who report adverse events as a measure of safety	6 months
Secondary	Change of HPV16 DNA titers	Blood samples will be taken at the indicated times	Baseline, 3 and 6 months
Secondary	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
Secondary	Change of cervical histological results	Colposcopy Biopsy will be conducted at the baseline and month 6 on each subject	Baseline and 6 months