Safety and Efficacy of GX-188E DNA Therapeutic Vaccine Administered by Electroporation After Observation

Study Overview
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Brief Summary
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This study is to follow up on the change of immune response by measuring HPV type 16/18 E6 and E7 specific T cell response and lesion condition in subjects who have administered in DNA-based therapeutic vaccine.

Detailed Description
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This is a follow-up study to investigate the change of immunogenicity and lesion condition in subjects with cervical intraepithelial neoplasia (CIN) 3 who have enrolled and participated GX-188E phase II trial(GX-188E_CIN3_P2). Subjects will make visits 7 times for about three years from the last visit of GX-188E phase 2 trial (GX-188E_CIN3_P2). The endpoints are to evaluate the change of immune response, involved lesion and infection status compared to that of the final visit in phase 2 trial (GX-188E_CIN3_P2).

Official Title
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A Prospective, Observational, Open-label, Multi-center, Follow-up Clinical Study to Determine Recurrence of Cervical Intraepithelial Neoplasia and Evaluate the Long-term Safety of GX-188E, a DNA-based Therapeutic Vaccine, Administered Intramuscularly by Electroporation (EP) in Subjects Who Were Diagnosed With HPV(Human Papillomavirus) 16 or 18 Positive Cervical Intraepithelial Neoplasia 3 (CIN 3) and Participated in Phase 2 Trial (GX-188E_CIN3_P2)

Conditions
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Cervical Intraepithelial Neoplasia 3

Intervention / Treatment
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* Biological: GX-188E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Those who voluntarily signed informed consent form The subjects who have participated in phase II trial(GX-188E_CIN3_P2) Exclusion Criteria: The subjects who didn't receive GX-188E DNA vaccine during Phase II trial (GX-188E_CIN3_P2) The subjects, it is difficult to participate in this study continuously Any other ineligible condition at the discretion of the investigator that would be ineligible to participate the study

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Observational group<br>Subjects in the period less than 24 weeks after the final administration of GX-188E | Biological: GX-188E<br>* In phase II study, 72 patients were assigned to two dose groups (1mg and 4mg) and were administered three times with GX-188E by electroporation during an entire period of study. After the final administration, the follow-up will be conducted to investigate safety and efficacy aspects.<br>* Other names: GX-188E administered by electrophoration;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessment examined by physical examination, vital signs, ECG, clinical laboratory test etc | long term safety assessment of GX-188E DNA vaccine of subjects participated in GX-188E_ CIN3_P2 clinical trial - Safety profile would be examined by physical examination, vital signs, ECG, clinical laboratory test etc | at week -18 and 130 | 
| lesion recurrence | The change of the CIN lesion (included cervical cancer) would be compared to that of the last visit in phase II study | at week -18 and 130 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of HPV infection status | The change of HPV infection status would be compared to that of the last visit in phase II study. | at week -18 and 130 | 
| The change of cytology test result | The change of cytology status would be compared to that of the last visit in phase II study. | at week -18 and 130 | 
| The change of the immune response | It would be determined by evaluating HPV type 16/18 E6 and E7 specific T cell response (IFN-γ ELISPOT: enzyme-linked immunospot assay) using PBMC(peripheral blood monocyte). | at week -18 and 130 | 
| Flt-3L(fms-related tyrosine kinase 3 ligand) concentration (Flt-3L ELISA) using plasma. | Pharmacodynamics evaluation of GX-188E | at week -18 and 130 | 
| Survey of pregnancy and delivery | The matters relevant to the subject of pregnancy and delivery would be collected by survey to identify occurence, frequency and characteristic. | at week -18 and 130 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adult, Phase 2 follow up, Cervical Intraepithelial Neoplasia, Safety, Efficacy