Human Papillomavirus-Related Malignant NeoplasmPhase 1NCT02800369
Study of Molecular-targeted Therapy Using Zinc Finger Nuclease in Cervical Precancerous Lesions
A Phase 1 study testing ZFN-603 and ZFN-758 in people with Human Papillomavirus-Related Malignant Neoplasm, run by Huazhong University of Science and Technology at 1 site in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 50 years, women only
- Conditions the study is for
- Human Papillomavirus-Related Malignant Neoplasm
- What is being tested?
- ZFN-603 and ZFN-758
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 10 Dec 2016to 10 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety Study of Zinc Finger Nucleases ZFN-602 and ZFN-758 in HPV-infected Subjects
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.
Read more
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.
Read the detailed description
Laboratory studies have shown that ZFN-603 and ZFN-758 could induce significant cleavage of E7 DNA in HPV16- and HPV18-positive cells. The disruption to viral DNA directly led to downregulation of E7 expression and restoration of the tumor suppressor genes retinoblastoma 1 (RB1), resulting in apoptosis and growth inhibition of ZFN-treated HPV16- and HPV18- positive cell lines. On the basis of these laboratory results, there is the potential that this may work in humans infected with high-risk HPV (especially HPV16 and HPV18) and block the progression of CIN The new treatment to be studied will involve transfecting ZFNs into HPV-infected cervical epithelials. Cells modified by ZFN-603 and ZFN-758 will lose the ability of immortalization and progress to apoptosis.
Researchers hope that these agents will be able to block the malignant progression of CIN and reduce the incidence of cervical cancer
- Being tested
- ZFN-603 and ZFN-758
- Keywords
- Human papillomavirus, cervical intraepithelial neoplasia, zinc finger nuclease
- Medical subject headings
- Uterine Cervical Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZFN-603 and ZFN-758Biological
Each suppository contain 500 µg of ZFN-603 or ZFN-758
| Study group | Role | What they receive |
|---|---|---|
| ZFN-603 and ZFN-758 | Experimental | Subjects will receive suppository with ZFN-603 or ZFN-758 Receives: Biological: ZFN-603 and ZFN-758 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Secondary outcomes (3)
Evaluate persistence of HPV16 and HPV18 as measured by HPV DNA
Reduce the virus titers after using ZFN-603 and ZFN-758
Measured: 6 months
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.
Measured: 6 months
Number of participants with Regain health or without progress
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2016 (estimated)
- Study start10 Dec 2016
- Primary completion10 Jun 2017
- Study completion10 Jul 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Human Papillomavirus-Related Malignant NeoplasmStudies of the same condition, open and under way.
- More trials run by Huazhong University of Science and TechnologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Huazhong University of Science and Technology
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ding Ma, Huazhong University of Science and Technology
- Investigators
- Hui Wang, M.D., Study director, Huazhong University of Science and TechnologyWencheng Ding, M.D., Principal investigator, Huazhong University of Science and TechnologyDa Zhu, M.D., Principal investigator, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02800369
- Sponsor's protocol ID
- 2016ZFN-V02
- Status last verified
- Jul 2017
- First submitted
- 1 Jun 2016
- Last updated
- 12 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 25336692
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety Study of Zinc Finger Nucleases ZFN-602 and ZFN-758 in HPV-infected Subjects
- ClinicalTrials.gov ID
- NCT02800369
- Acronym / sponsor ID
- 2016ZFN-V02
- Keywords
- Human papillomavirus, cervical intraepithelial neoplasia, zinc finger nuclease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Huazhong University of Science and TechnologyUniversity, hospital or other
- Study start
- 10 Dec 2016 (actual)
- Primary completion
- 10 Jun 2017 (actual)
- Study completion
- 10 Jul 2017 (estimated)
- First posted
- 15 Jun 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Laboratory studies have shown that ZFN-603 and ZFN-758 could induce significant cleavage of E7 DNA in HPV16- and HPV18-positive cells. The disruption to viral DNA directly led to downregulation of E7 expression and restoration of the tumor suppressor genes retinoblastoma 1 (RB1), resulting in apoptosis and growth inhibition of ZFN-treated HPV16- and HPV18- positive cell lines. On the basis of these laboratory results, there is the potential that this may work in humans infected with high-risk HPV (especially HPV16 and HPV18) and block the progression of CIN The new treatment to be studied will involve transfecting ZFNs into HPV-infected cervical epithelials. Cells modified by ZFN-603 and ZFN-758 will lose the ability of immortalization and progress to apoptosis.
Researchers hope that these agents will be able to block the malignant progression of CIN and reduce the incidence of cervical cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ZFN-603 and ZFN-758 | Experimental | Biological: ZFN-603 and ZFN-758Subjects will receive suppository with ZFN-603 or ZFN-758 |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (12 listed)
- Pregnancy and breast feeding
- Any bacterial vaginitis
- Any Fungal vaginitis
- Any sexually transmitted diseases
- Active drug or alcohol abuse
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZFN-603 and ZFN-758Each suppository contain 500 µg of ZFN-603 or ZFN-758 | Biological | ZFN-603 and ZFN-758 |
Primary outcome
Safety - Treatment related adverse events of ZFN-603 in HPV16-positive subjects, related adverse events of ZFN-758 in HPV18-positive subjects
Time frame: 6 months
Number of participants who report adverse events as a measure of safety
3 secondary outcomes
Evaluate persistence of HPV16 and HPV18 as measured by HPV DNA
Time frame: 6 months
Change in the number of dysplastic cells as mearsured by ThinPrep Pap Test
Time frame: 6 months
Number of participants with Regain health or without progress
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2017.
- Background: PubMed 25336692Ding 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hui Wang, M.D. study director
Huazhong University of Science and Technology
Wencheng Ding, M.D. principal investigator
Huazhong University of Science and Technology
Da Zhu, M.D. principal investigator
Huazhong University of Science and Technology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ZFN-603 and ZFN-758 in people with Human Papillomavirus-Related Malignant Neoplasm, run by Huazhong University of Science and Technology at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety - Treatment related adverse events of ZFN-603 in HPV16-positive subjects, related adverse events of ZFN-758 in HPV18-positive subjects (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02800369, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2017.