Human Papillomavirus-Related Malignant NeoplasmPhase 1NCT03057912
A Safety and Efficacy Study of TALEN and CRISPR/Cas9 in the Treatment of HPV-related Cervical Intraepithelial NeoplasiaⅠ
A Phase 1 study testing TALEN and CRISPR/Cas9 in people with Human Papillomavirus-Related Malignant Neoplasm, run by First Affiliated Hospital, Sun Yat-Sen University at 1 site in China.
Trial summary
This is an open-label and triple cohort study of the safety and efficacy of TALEN and CRISPR/Cas9 to possibly treat HPV Persistency and human cervical intraepithelial neoplasiaⅠwithout invasion. 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?
- TALEN and CRISPR/Cas9
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 15 Jan 2018to 15 Jan 2019
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
China1 site
The First Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510080
Zheng Hu, M.D., 0086+18627803527, 18627803527@163.com
About this study
Official title: A Safety and Efficacy Study of Transcription Activator-like Effector Nucleases and Clustered Regularly Interspaced Short Palindromic Repeat/Cas9 in the Treatment of HPV-related Cervical Intraepithelial NeoplasiaⅠ
This is an open-label and triple cohort study of the safety and efficacy of TALEN and CRISPR/Cas9 to possibly treat HPV Persistency and human cervical intraepithelial neoplasiaⅠwithout invasion.
Read the detailed description
HPV persistent infection is the major causal factor of cervical intraepithelial neoplasia (CIN) and cervical cancer. The important roles of E6 and E7 playing in HPV-driven carcinogenesis make them attractive targets for therapeutic interventions. Previous evidences showed that using designated TALEN and CRISPR/Cas9 as genome editing tool could produce disruption of HPV16 and HPV18 E6/E7 DNA, significantly decreasing the expression of E6/E7, inducing cell apoptosis and inhibiting cell lines growth.
This study will evaluate the safety and efficacy of TALEN-HPV E6/E7 and CRISPR/Cas9-HPV E6/E7 in treating HPV Persistency and HPV-related Cervical Intraepithelial NeoplasiaⅠ
- Being tested
- TALEN, CRISPR/Cas9
- Keywords
- Cervical intraepithelial neoplasiaⅠ, TALEN, CRISPR/Cas9
- 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.
TALENBiological
Also called TALEN-HPV16 E6/E7;TALEN-HPV18 E6/E7
TALEN gel consists of TALEN plasmid, C32-447, Poloxmer 407 and distilled water as solvent.
CRISPR/Cas9Biological
Also called CRISPR/Cas9-HPV16 E6/E7T1;CRISPR/Cas9-HPV18 E6/ E7T2
CRISPR/Cas9 gel consists of CRISPR/Cas9 plasmid, C32-447, Poloxmer 407 and distilled water as solvent.
| Study group | Role | What they receive |
|---|---|---|
| TALEN | Experimental | TALEN (TALEN-HPV16 E6/E7 or TALEN-HPV18 E6/E7) plasmid in gel, administered twice one week for 4 weeks. Receives: Biological: TALEN |
| CRISPR/Cas9 | Experimental | CRISPR/Cas9 (CRISPR/Cas9-HPV16 E6/E7T1 or CRISPR/Cas9-HPV18 E6/E7T2 ）plasmid in gel, administered twice one week for 4 weeks. Receives: Biological: CRISPR/Cas9 |
| Control group | No intervention | Observation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with Adverse Events
The primary objective of this Study is to evaluate the safety of therapeutic doses and the dosing regimen of TALEN and CRISPR/Cas9 plasmid.
Measured: 6 months
Secondary outcomes (3)
Change of HPV16 or 18 DNA titers
Blood samples will be taken at the baseline, months 3 and 6 on each subject.
Measured: Baseline, 3 and 6 months
Change of cervical cytological results.
ThinPrep Pap Test will be conducted at the baseline, months 3 and 6 on each subject.
Measured: Baseline, 3 and 6 months
Change of cervical histological results.
Colposcopy Biopsy will be conducted at the baseline and month 6 on each subject.
Measured: Baseline and 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2017
- Study start15 Jan 2018 (estimated)
- Primary completion15 Nov 2018 (estimated)
- Study completion15 Jan 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Human Papillomavirus-Related Malignant NeoplasmStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- First Affiliated Hospital, Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Jingchu University of Technology
- Responsible party
- Principal investigator, Hu Zheng, First Affiliated Hospital, Sun Yat-Sen University
- Investigators
- Zheng Hu, M.D., Principal investigator, First Affiliated Hospital, Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03057912
- Sponsor's protocol ID
- 2017CRISPR/Cas9&TALEN
- Status last verified
- Jun 2017
- First submitted
- 12 Feb 2017
- Last updated
- 9 Jun 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Hu Z, Yu L, Zhu D, Ding W, Wang X, Zhang C, Wang L, Jiang X, Shen H, He D, Li K, Xi L, Ma D, Wang H. Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. Biomed Res Int. 2014;2014:612823. doi: 10.1155/2014/612823. Epub 2014 Jul 20.
PubMed 25136604Hu 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.
PubMed 25500889
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety and Efficacy Study of Transcription Activator-like Effector Nucleases and Clustered Regularly Interspaced Short Palindromic Repeat/Cas9 in the Treatment of HPV-related Cervical Intraepithelial NeoplasiaⅠ
- ClinicalTrials.gov ID
- NCT03057912
- Acronym / sponsor ID
- 2017CRISPR/Cas9&TALEN
- Keywords
- Cervical intraepithelial neoplasiaⅠ, TALEN, CRISPR/Cas9
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- First Affiliated Hospital, Sun Yat-Sen UniversityUniversity, hospital or other
- Collaborators
- Jingchu University of Technology
- Study start
- 15 Jan 2018 (estimated)
- Primary completion
- 15 Nov 2018 (estimated)
- Study completion
- 15 Jan 2019 (estimated)
- First posted
- 20 Feb 2017 (actual)
- 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 is an open-label and triple cohort study of the safety and efficacy of TALEN and CRISPR/Cas9 to possibly treat HPV Persistency and human cervical intraepithelial neoplasiaⅠwithout invasion.
Detailed description
HPV persistent infection is the major causal factor of cervical intraepithelial neoplasia (CIN) and cervical cancer. The important roles of E6 and E7 playing in HPV-driven carcinogenesis make them attractive targets for therapeutic interventions. Previous evidences showed that using designated TALEN and CRISPR/Cas9 as genome editing tool could produce disruption of HPV16 and HPV18 E6/E7 DNA, significantly decreasing the expression of E6/E7, inducing cell apoptosis and inhibiting cell lines growth.
This study will evaluate the safety and efficacy of TALEN-HPV E6/E7 and CRISPR/Cas9-HPV E6/E7 in treating HPV Persistency and HPV-related Cervical Intraepithelial NeoplasiaⅠ
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| TALEN | Experimental | Biological: TALENTALEN (TALEN-HPV16 E6/E7 or TALEN-HPV18 E6/E7) plasmid in gel, administered twice one week for 4 weeks. |
| CRISPR/Cas9 | Experimental | Biological: CRISPR/Cas9CRISPR/Cas9 (CRISPR/Cas9-HPV16 E6/E7T1 or CRISPR/Cas9-HPV18 E6/E7T2 ）plasmid in gel, administered twice one week for 4 weeks. |
| Control group | No intervention | –Observation |
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 |
|---|---|---|
| TALENAlso: TALEN-HPV16 E6/E7;TALEN-HPV18 E6/E7TALEN gel consists of TALEN plasmid, C32-447, Poloxmer 407 and distilled water as solvent. | Biological | TALEN |
| CRISPR/Cas9Also: CRISPR/Cas9-HPV16 E6/E7T1;CRISPR/Cas9-HPV18 E6/ E7T2CRISPR/Cas9 gel consists of CRISPR/Cas9 plasmid, C32-447, Poloxmer 407 and distilled water as solvent. | Biological | CRISPR/Cas9 |
Primary outcome
Number of participants with Adverse Events
Time frame: 6 months
The primary objective of this Study is to evaluate the safety of therapeutic doses and the dosing regimen of TALEN and CRISPR/Cas9 plasmid.
3 secondary outcomes
Change of HPV16 or 18 DNA titers
Time frame: Baseline, 3 and 6 months
Change of cervical cytological results.
Time frame: Baseline, 3 and 6 months
Change of cervical histological results.
Time frame: Baseline and 6 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jun 2017.
- Background: PubMed 25136604Hu Z, Yu L, Zhu D, Ding W, Wang X, Zhang C, Wang L, Jiang X, Shen H, He D, Li K, Xi L, Ma D, Wang H. Disruption of HPV16-E7 by CRISPR/Cas system induces apoptosis and growth inhibition in HPV16 positive human cervical cancer cells. Biomed Res Int. 2014;2014:612823. doi: 10.1155/2014/612823. Epub 2014 Jul 20.
- Background: PubMed 25500889Hu 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.
- 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.
Zheng Hu, M.D. principal investigator
First Affiliated Hospital, Sun Yat-Sen University
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 TALEN and CRISPR/Cas9 in people with Human Papillomavirus-Related Malignant Neoplasm, run by First Affiliated Hospital, Sun Yat-Sen University 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 9 Jun 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?
Contact Zheng Hu, M.D. (0086+18627803527, 18627803527@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with Adverse Events (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 NCT03057912, which also lists 2 linked publications.
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 9 Jun 2017; AzTrials last refreshed its copy on 26 Oct 2026.