Dose-finding, Safety Study of Plasmid DNA Therapeutic Vaccine to Treat Cervical Intraepithelial Neoplasia

Study Overview
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Brief Summary
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The purpose of this study is to determine the optimal dose of GX-188E for the Phase 3 and access the efficacy and safety of GX-188E according the protocol in patients with Cervical Intraepithelial Neoplasia 3 (CIN3).

Detailed Description
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Subjects who are eligible for this study are allocated to one of the two treatment groups of GX-188E. All Subject received GX-188E intramuscularly using the electroporator(EP) on alternating deltoid muscles which will be performed totally three times during the study period.

Official Title
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A Randomized, Open-label, Multi-center, Phase 2 Clinical Trial to Determine the Optimal Dose and Evaluate the Safety of GX-188E, a DNA-based Therapeutic Vaccine, Administered Intramuscularly by Electroporation (EP) in HPV Type 16 and/or 18 Positive Patients With Cervical Intraepithelial Neoplasia 3 (CIN 3)

Conditions
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Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Biological: GX-188E


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily signed informed consent form after receiving education about this study and the investigational product. Female aged between 19 and 50 years Positive test results for HPV Type 16 and/or Type 18 Histopathologically-confirmed Cervical Intraepithelial Neoplasia 3 Entire cervical area including entire squamocolumnar junction is visualized through colposcopy Eligible based on screening test results. Promised not to get pregnant throughout the study Exclusion Criteria: Suspected Adenocarcinoma in situ Malignant cancer more than Stage I Pregnancy or breastfeeding Participation in clinical trials within 30 days of the screening visit Administration of immunosuppressant or immunomodulator within 6 months prior to the enrolment Administered with systemic steroid(as a standard with Prednisolone, more than 20mg/day for every 14 days or more) within 3 months of Day 1(including ointment, eye drops, inhalated or nasal, intra-ligamental or intra-articular injection, but not applicable if injected every other day Administered any blood products within 3 months prior to the screening visit Administered any vaccine within 4 weeks prior to the screening visit(ex. Hepatitis A, Hepatitis B, Influenza, Td etc.) Positive serum test results for hepatitis C virus, hepatitis B virus surface antigen(HBsAg) or HIV Severe hepatopathy which is Class C according to Child-Pough's classification Severe renal dysfunction where the creatinine clearance(CLcr) is lower than 30ml/min CPK test results more than 2.5 times the upper limit of normal Predisposed to inflammatory reaction due to use of medical devices such as electroporation within 30 days of screening visit History of severe adverse drug events or severe allergic diseases History of epilepsy or convulsion within 2 years prior to the screening visit At the discretion of the investigator, the skin condition covering deltoid muscles, within 2cm of the intended sites of injection, is not suitable for injection due to infection, ulcer, edema, tattoo, scar, injury etc. The thickness of skin fold covering deltoid muscles, intended injection sites, > 40mm Any orthopedic artificial implant around the intended sites of electroporation (deltoid muscles) Sinus bradycardia whose resting heart rate < 50 beats/min Pre-excitation syndrome such as Wolff-Parkinson-White syndrome Abnormal electrocardiography(ECG) including arrhythmia Artificial implants or metallic implants 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1mg of GX-188E per dose<br>1mg of GX-188E per dose will be administered on 1mg group participants through intramuscular route using EP device. The injection points are at 0 week, 4 week and 12 week. | Biological: GX-188E<br>* DNA vaccine administered via IM route using TDS-IM electroporation device<br>* Other names: DNA therapeutic vaccine;|
| Experimental: 4mg of GX-188E per dose<br>4mg of GX-188E per dose will be administered on 4mg group participants through intramuscular route using EP device. The injection points are at 0 week, 4 week and 12week. | Biological: GX-188E<br>* DNA vaccine administered via IM route using TDS-IM electroporation device<br>* Other names: DNA therapeutic vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Rate of Participants with Histopathological Regression of Cervical Lesions to CIN1 or Less |  | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Rate of Participants Whose Result Inverted Negative in HPV DNA test |  | 20 weeks | 
| The rate of HPV E6, E7-specific ELISPOT responder defined in the protocol |  | 20 weeks | 
| Cytological Changes of the Cervical Lesions |  | 20 weeks | 
| The Rate of Adverse Events and the Related Features after Administration of Investigational Product |  | 20 weeks | 
| The Rate of Solicited Adverse Events and the Related Features |  | 20 weeks | 
| Data in Physical examination, Vital signs, Electrocardiography, Clinical Laboratory Test Results Related to Investigational Product |  | 20 weeks | 
| Mean Value of Visual Analogue Scale on Pain Intensity |  | 20 weeks | 
| Flt-3L Serum Concentration |  | 20 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CIN3, Cervical Intraepithelial Neoplasia, High-Risk HPV, HPV Infection, Neoplasm, Precancerous Diseases, Uterine Diseases, Genital Diseases, Female