NCT02800369

Study of Molecular-targeted Therapy Using Zinc Finger Nuclease in Cervical Precancerous Lesions

Status unknown Phase 1 Last updated 12 July 2017

What this trial tests

Phase 1 trial testing ZFN-603 and ZFN-758 in Human Papillomavirus-Related Malignant Neoplasm in 20 participants. Status unknown.

Timeline

10 December 2016

Primary endpoint
10 June 2017

10 July 2017

Quick facts

Lead sponsor	Huazhong University of Science and Technology
Phase	Phase 1
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	20
Start date	10 December 2016
Primary completion	10 June 2017
Estimated completion	10 July 2017
Sites	1 location across China

Drugs / interventions tested

• ZFN-603 and ZFN-758 — full drug profile →

Conditions studied

• Human Papillomavirus-Related Malignant Neoplasm — all drugs for Human Papillomavirus-Related Malignant Neoplasm →

Sponsor

Huazhong University of Science and Technology

Who can join

Adults 18 to 50, female only, with Human Papillomavirus-Related Malignant Neoplasm. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This research study is being carried out to study a new way to possibly treat human cervical intraepithelial neoplasia (CIN) without invasion.

Persistent infection with specific types of human papillomavirus (HPV, most frequently types 16 and 18) may lead to precancerous lesions(CIN). If untreated, these lesions may progress to cervical cancer within many years. In the infected cells, HPV expresses the oncoproteins E6 and E7, both of which play key roles in maintaining viral infection and promoting carcinogenesis. Previous studies has demonstrated that E7 alone, but not E6, is sufficient to immortalize human keratinocytes in vitro and induce high-grade cervical dysplasia in a transgenic mouse model. These data indicated that E7 may dominate the malignant progress in HPV-infected cells.

The agents zinc finger nucleases (ZFNs), called ZFN-603 and ZFN-758, which can cleave the HPV16 and HPV18 E7 oncogene specifically. ZFN-mediated disruption of HPV16 and HPV18 E7 DNA directly decreased the expression of E7, induced type-specific apoptosis in HPV16- and HPV18-positive cells, and inhibited cell growth.

The purpose of this study is to determine whether ZFN-603 and ZFN-758 are effective in the treatment of HPV16- and HPV18-positive cervical intraepithelial neoplasia.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects.
   Li H, Yang Y, Hong W, Huang M, et al · · 2020 · cited 733× · PMID 32296011 · DOI 10.1038/s41392-019-0089-y
2. Biological and clinical aspects of HPV-related cancers.
   Szymonowicz KA, Chen J. · · 2020 · cited 255× · PMID 33299640 · DOI 10.20892/j.issn.2095-3941.2020.0370
3. CRISPR-Cas systems: Overview, innovations and applications in human disease research and gene therapy.
   Xu Y, Li Z. · · 2020 · cited 202× · PMID 33005303 · DOI 10.1016/j.csbj.2020.08.031
4. Therapeutic vaccines for high-risk HPV-associated diseases.
   Chabeda A, Yanez RJR, Lamprecht R, Meyers AE, et al · · 2018 · cited 148× · PMID 29277575 · DOI 10.1016/j.pvr.2017.12.006
5. Gene editing and CRISPR in the clinic: current and future perspectives.
   Hirakawa MP, Krishnakumar R, Timlin JA, Carney JP, et al · · 2020 · cited 126× · PMID 32207531 · DOI 10.1042/bsr20200127
6. Therapeutic gene editing: delivery and regulatory perspectives.
   Shim G, Kim D, Park GT, Jin H, et al · · 2017 · cited 78× · PMID 28392568 · DOI 10.1038/aps.2017.2
7. Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease.
   Ernst MPT, Broeders M, Herrero-Hernandez P, Oussoren E, et al · · 2020 · cited 67× · PMID 32775490 · DOI 10.1016/j.omtm.2020.06.022
8. Gene editing and its applications in biomedicine.
   Li G, Li X, Zhuang S, Wang L, et al · · 2022 · cited 44× · PMID 35235150 · DOI 10.1007/s11427-021-2057-0