Human Papillomavirus-Related Malignant Neoplasm Clinical Trial
Official title:
Safety Study of Zinc Finger Nucleases ZFN-602 and ZFN-758 in HPV-infected Subjects
Verified date | July 2017 |
Source | Huazhong University of Science and Technology |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 20 |
Est. completion date | July 10, 2017 |
Est. primary completion date | June 10, 2017 |
Accepts healthy volunteers | No |
Gender | Female |
Age group | 18 Years to 50 Years |
Eligibility |
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 trail or any prior gene therapy |
Country | Name | City | State |
---|---|---|---|
China | Tongji Hospital | Wuhan | Hubei |
Lead Sponsor | Collaborator |
---|---|
Huazhong University of Science and Technology |
China,
Ding W, Hu Z, Zhu D, Jiang X, Yu L, Wang X, Zhang C, Wang L, Ji T, Li K, He D, Xia X, Liu D, Zhou J, Ma D, Wang H. Zinc finger nucleases targeting the human papillomavirus E7 oncogene induce E7 disruption and a transformed phenotype in HPV16/18-positive cervical cancer cells. Clin Cancer Res. 2014 Dec 15;20(24):6495-503. doi: 10.1158/1078-0432.CCR-14-0250. Epub 2014 Oct 21. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Safety - Treatment related adverse events of ZFN-603 in HPV16-positive subjects, related adverse events of ZFN-758 in HPV18-positive subjects | Number of participants who report adverse events as a measure of safety | 6 months | |
Secondary | Evaluate persistence of HPV16 and HPV18 as measured by HPV DNA | Reduce the virus titers after using ZFN-603 and ZFN-758 | 6 months | |
Secondary | Change in the number of dysplastic cells as mearsured by ThinPrep Pap Test | From high-grade squamous intraepithelial lesion (HSIL) to Low-grade Squamous Intraepithelial Lesion (LSIL), or from LSIL to negative. | 6 months | |
Secondary | Number of participants with Regain health or without progress | 6 months |
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