NCT03057912

Brief 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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
60

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2018

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 12, 2017

Completed
8 days until next milestone

First Posted

Study publicly available on registry

February 20, 2017

Completed
11 months until next milestone

Study Start

First participant enrolled

January 15, 2018

Completed
10 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 15, 2018

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 15, 2019

Completed
Last Updated

June 9, 2017

Status Verified

June 1, 2017

Enrollment Period

10 months

First QC Date

February 12, 2017

Last Update Submit

June 7, 2017

Conditions

Human Papillomavirus-Related Malignant Neoplasm

Keywords

Cervical intraepithelial neoplasiaⅠTALENCRISPR/Cas9

Outcome Measures

Primary Outcomes (1)

  • 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.

    6 months

Secondary Outcomes (3)

  • Change of HPV16 or 18 DNA titers

    Baseline, 3 and 6 months

  • Change of cervical cytological results.

    Baseline, 3 and 6 months

  • Change of cervical histological results.

    Baseline and 6 months.

Study Arms (3)

TALEN

EXPERIMENTAL

TALEN (TALEN-HPV16 E6/E7 or TALEN-HPV18 E6/E7) plasmid in gel, administered twice one week for 4 weeks.

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.

Biological: CRISPR/Cas9

Control group

NO INTERVENTION

Observation

Interventions

TALENBIOLOGICAL

TALEN gel consists of TALEN plasmid, C32-447, Poloxmer 407 and distilled water as solvent.

Also known as: TALEN-HPV16 E6/E7;TALEN-HPV18 E6/E7
TALEN
CRISPR/Cas9BIOLOGICAL

CRISPR/Cas9 gel consists of CRISPR/Cas9 plasmid, C32-447, Poloxmer 407 and distilled water as solvent.

Also known as: CRISPR/Cas9-HPV16 E6/E7T1;CRISPR/Cas9-HPV18 E6/ E7T2
CRISPR/Cas9

Eligibility Criteria

Age18 Years - 50 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

The First Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Related Publications (2)

  • 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.

    PMID: 25136604BACKGROUND

  • 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.

    PMID: 25500889BACKGROUND

MeSH Terms

Conditions

Uterine Cervical Dysplasia

Interventions

Transcription Activator-Like Effector NucleasesCRISPR-Associated Protein 9

Condition Hierarchy (Ancestors)

Precancerous ConditionsNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Diseases

Intervention Hierarchy (Ancestors)

EndodeoxyribonucleasesDeoxyribonucleasesEsterasesHydrolasesEnzymesEnzymes and CoenzymesRecombinant Fusion ProteinsRecombinant ProteinsProteinsAmino Acids, Peptides, and ProteinsEndonucleasesBacterial ProteinsCRISPR-Associated Proteins

Study Officials

  • Zheng Hu, M.D.

    First Affiliated Hospital, Sun Yat-Sen University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Zheng Hu, M.D.

CONTACT

0086+1862780352718627803527@163.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Masking Details
open label
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

February 12, 2017

First Posted

February 20, 2017

Study Start

January 15, 2018

Primary Completion

November 15, 2018

Study Completion

January 15, 2019

Last Updated

June 9, 2017

Record last verified: 2017-06

Locations

CN(1)