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

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)

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).

Study Overview

• Status: Completed
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Biological: GX-188E

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of, 700-712
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of, 152-703
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of, 100-380
    • Cheil General Hospital & Women's Healthcare Center
  • Seoul, Korea, Republic of, 137-701
    • The Catholic University of Korea Seoul St.Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Voluntarily signed informed consent form after receiving education about this study and the investigational product.
2. Female aged between 19 and 50 years
3. Positive test results for HPV Type 16 and/or Type 18
4. Histopathologically-confirmed Cervical Intraepithelial Neoplasia 3
5. Entire cervical area including entire squamocolumnar junction is visualized through colposcopy
6. Eligible based on screening test results.
7. Promised not to get pregnant throughout the study

Exclusion Criteria:

1. Suspected Adenocarcinoma in situ
2. Malignant cancer more than Stage I
3. Pregnancy or breastfeeding
4. Participation in clinical trials within 30 days of the screening visit
5. Administration of immunosuppressant or immunomodulator within 6 months prior to the enrolment
6. 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
7. Administered any blood products within 3 months prior to the screening visit
8. Administered any vaccine within 4 weeks prior to the screening visit(ex. Hepatitis A, Hepatitis B, Influenza, Td etc.)
9. Positive serum test results for hepatitis C virus, hepatitis B virus surface antigen(HBsAg) or HIV
10. Severe hepatopathy which is Class C according to Child-Pough's classification
11. Severe renal dysfunction where the creatinine clearance(CLcr) is lower than 30ml/min
12. CPK test results more than 2.5 times the upper limit of normal
13. Predisposed to inflammatory reaction due to use of medical devices such as electroporation within 30 days of screening visit
14. History of severe adverse drug events or severe allergic diseases
15. History of epilepsy or convulsion within 2 years prior to the screening visit
16. 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.
17. The thickness of skin fold covering deltoid muscles, intended injection sites, > 40mm
18. Any orthopedic artificial implant around the intended sites of electroporation (deltoid muscles)
19. Sinus bradycardia whose resting heart rate < 50 beats/min
20. Pre-excitation syndrome such as Wolff-Parkinson-White syndrome
21. Abnormal electrocardiography(ECG) including arrhythmia
22. Artificial implants or metallic implants
23. Any other ineligible condition at the discretion of the investigator that would be ineligible to participate the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1mg of GX-188E per dose; 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; DNA vaccine administered via IM route using TDS-IM electroporation device; Other Names: DNA therapeutic vaccine
Experimental: 4mg of GX-188E per dose; 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; DNA vaccine administered via IM route using TDS-IM electroporation device; Other Names: DNA therapeutic vaccine

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Genexine, Inc.
• Investigators: Principal Investigator: Park Jong-Sup, M.D., The Catholic University of Korea; Principal Investigator: Kim Tae-Jin, M.D., Cheil General Hospital & Women's Healthcare Center; Principal Investigator: Lee Jae-kwan, M.D., Korea University Guro Hospital; Principal Investigator: Cho Chi-heum, M.D., Keimyung University Dongsan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: May 13, 2014
• First Submitted That Met QC Criteria: May 13, 2014
• First Posted (Estimate): May 15, 2014

Study Record Updates

• Last Update Posted (Actual): July 12, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Cervical Intraepithelial Neoplasia; Neoplasm; HPV Infection; Genital Diseases, Female; CIN3; Uterine Diseases; High-Risk HPV; Precancerous Diseases
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms; Carcinoma in Situ; Cervical Intraepithelial Neoplasia; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: GX-188E_CIN3_P2