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

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

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

Study Overview

• Status: Recruiting
• Conditions: Human Papillomavirus-Related Malignant Neoplasm
• Intervention / Treatment: Biological: T512

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ding Ma, M.D.; Phone Number: 86-27-83662681; Email: dma@tjh.tjmu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Recruiting
      • Tongji Hospital
      • Contact: Ding Ma, M.D.; Phone Number: 86-27-83662681; Email: dma@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Huazhong University of Science and Technology

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2017
• Primary Completion (Anticipated): February 10, 2022
• Study Completion (Anticipated): June 10, 2022

Study Registration Dates

• First Submitted: July 17, 2017
• First Submitted That Met QC Criteria: July 19, 2017
• First Posted (Actual): July 21, 2017

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: December 29, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: cervical intraepithelial neoplasia; Human papillomavirus; Transcription Activator-like Effector Nucleases
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 2017TALEN-V02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No