Clinical trial NCT02139267: Dose-finding, Safety Study of Plasmid DNA Therapeutic Vaccine to Treat Cervical Intraepithelial Neoplasia
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Intraepithelial Neoplasia
Keywords: CIN3
Cervical Intraepithelial Neoplasia
High-Risk HPV
HPV Infection
Neoplasm
Precancerous Diseases
Uterine Diseases
Genital Diseases, Female
Lead sponsor: Genexine, Inc.
Sponsor class: INDUSTRY
First posted: 2014-05-15
Enrollment: 72
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Rate of Participants with Histopathological Regression of Cervical Lesions to CIN1 or Less
timeFrame: 20 weeks
Secondary outcomes:
measure: The Rate of Participants Whose Result Inverted Negative in HPV DNA test
timeFrame: 20 weeks
measure: The rate of HPV E6, E7-specific ELISPOT responder defined in the protocol
timeFrame: 20 weeks
measure: Cytological Changes of the Cervical Lesions
timeFrame: 20 weeks
measure: The Rate of Adverse Events and the Related Features after Administration of Investigational Product
timeFrame: 20 weeks
measure: The Rate of Solicited Adverse Events and the Related Features
timeFrame: 20 weeks
measure: Data in Physical examination, Vital signs, Electrocardiography, Clinical Laboratory Test Results Related to Investigational Product
timeFrame: 20 weeks
measure: Mean Value of Visual Analogue Scale on Pain Intensity
timeFrame: 20 weeks
measure: Flt-3L Serum Concentration
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Seoul
country: Korea, Republic of
facility: Cheil General Hospital & Women's Healthcare Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
Study officials:
affiliation: The Catholic University of Korea
name: Park Jong-Sup, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Cheil General Hospital & Women's Healthcare Center
name: Kim Tae-Jin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Guro Hospital
name: Lee Jae-kwan, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Keimyung University Dongsan Medical Center
name: Cho Chi-heum, M.D.
role: PRINCIPAL_INVESTIGATOR
References: