Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of Plasmid DNA Therapeutic Vaccine(GX-188E)

A Randomized, Double-blind, Placebo-controlled, Multi-center, Phase 2 Clinical Trial to Evaluate the Efficacy and 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 Biopsy-proven Cervical Intraepithelial Neoplasia Grade 2(CIN2), Grade 2/3 (CIN2/3), Grade 3(CIN3)

The purpose of this study is to access the efficacy and safety of GX-188E according the protocol in patients with Cervical Intraepithelial Neoplasia 2, 2/3 or 3 (CIN3)

Study Overview

• Status: Unknown
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Biological: GX-188E; Biological: Placebo

Detailed Description

Not provided

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 2

Contacts and Locations

Study Locations

• Estonia
  • Tallinn, Estonia, 13419
    • North Estonia Medical Centre Foundation
  • Tallinn, Estonia, 10119
    • East Tallinn Central Hospital
  • Tartu, Estonia, 51014
    • Tartu University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Daegu, Korea, Republic of, 41931
    • Keimyung University Dongsan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 04619
    • Cheil General Hospital & Women's Healthcare Center
  • Seoul, Korea, Republic of, 06135
    • CHA Gangnam Medical Center
  • Seoul, Korea, Republic of, 07985
    • Ehwa Womans University Mokdong Hospital
  • Seoul, Korea, Republic of, 080308
    • Korea University Guro Hospital
• Ukraine
  • Kharkiv, Ukraine, 61070
    • Kharkiv Medical Academy of Postgraduate Education
  • Kyiv, Ukraine, 04050
    • National Academy of Medical Sciences of Ukraine
  • Odessa, Ukraine, 65026
    • Multi-profile Medical Center (University Clinic No. 1) of Odesa National
  • Zaporizhzhya, Ukraine, 69071
    • State Institution Zaporizhzhia Medical Academy of Post-Graduate Education

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female subjects age 18-60 years
2. Histologically confirmed HPV-16 or HPV-18 asspcoated CIN2, CIN 2/3 or CIN3 from tissue collected less than 10 weeks prior to Vaccination/EP #1 with overall lesion sizes less than 50% of the cervix area and no evidence of invasive cancer in any specimen;
3. Colposcopy is satisfactory based on visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area;
4. Healthy subjects as judged by the Investigator based on medical history, PE, and normal results for an ECG, CBC, Serum Chemistries, CPK and urinalysis done up to 4 weeks prior to enrolment;
5. For women who are not postmenopausal (at least 12 months of nontherapy- induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use a highly effective method of contraception during the treatment period and throughout Week 36 response evaluation visit.
6. Able and willing to comply with all study procedures and voluntarily signs informed consent form.

Exclusion Criteria:

1. Unsatisfactory colposcopy defined as incomplete visualization of the entire squamocolumnar junction and the upper limit of the entire aceto-white or suspected CIN disease area;
2. Pregnancy or breastfeeding;
3. Immunosuppression including any concurrent condition requiring the continued use of systemic or topical steroids at or near the injection site [deltoid, upper arm] (excluding inhaled and eye drop-containing corticosteroids) or the use of immunosuppressive agents. All other corticosteroids must be discontinued > 4 weeks prior to Day 0 of study vaccine administration; autoimmune disorders, transplant recipients;
4. History of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines (e.g. Gardasil®, Cervarix®) are not excluded);
5. Positive serological test for hepatitis C virus or hepatitis B virus surface antigen (HBsAg) or human immunodeficiency virus (HIV);
6. Administration of any blood product within 3 months of enrollment;
7. Administration of any licensed vaccine within 2 weeks of enrollment (4 weeks for measles vaccine);
8. Participation in a study with an investigational compound or device within 30 days prior to signing informed consent;
9. Cardiac pre-excitation syndromes (such as Wolff-Parkinson-White);
10. History of seizures (unless seizure free for 5 years);
11. Tattoos, scars, active lesions/rashes or any implantable leads within 3 cm of the intended site of vaccination/EP;
12. Any electronic medical implants (such as cardiac pacemaker);
13. Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements;
14. A tendency for severe haemorrhage following acute trauma;
15. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (i.e. infections disease) illness must not be enrolled into this study;
16. Any other conditions judged by the investigator that would limit the evaluation of a subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GX-188E; GX-188E + EP	Biological: GX-188E; 1mg of GX-188E administered IM using EP device at day 0, week 4 and week 12.; Other Names: DNA therapeutic vaccine
Placebo Comparator: placebo; Placebo + EP	Biological: Placebo; 0.5mL of Placebo administered IM using EP device at day 0, week 4 and week 12.; Other Names: Placebo-control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with histopathological regression of cervical lesions to CIN1 or less	The number of participants with cervical lesions regress to CIN1 or less at the 36 week visit	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Clearance of HPV 16 or 18 in combination with histopathological regression of cervical lesions to CIN1 or less	The number of participants with clearance of HPV 16 or 18 in combination with histopathological regression of cervical lesions to CIN1 or less at the 36 week visit	36 weeks

Collaborators and Investigators

• Sponsor: Genexine, Inc.
• Investigators: Principal Investigator: Terje Raud, MD, Tartu University Hospital; Principal Investigator: Kersti Kukk, MD, North Estonia Medical Centre Foundation; Principal Investigator: Aira Peri, MD, East Tallinn Central Hospital; Principal Investigator: Tetiana Tatarchuk, MD, National Academy of Medical Sciences of Ukraine; Principal Investigator: Nataliya Lutsenko, MD, State Institution, Zaporizhzhia Medical Academy of Post-Graduate Education Ministry of Health of Ukraine; Principal Investigator: Sergiy Kartashov, MD, Kharkiv Medical Academy of Postgraduate Education; Principal Investigator: Natalia Rozhkovska, MD, Multi-profile Medical Center (University Clinic No. 1) of Odesa National Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2015
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): August 1, 2018

Study Registration Dates

• First Submitted: November 3, 2015
• First Submitted That Met QC Criteria: November 3, 2015
• First Posted (Estimate): November 4, 2015

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; Double Blind; HPV infection; Safety/Efficacy; CIN2, CIN2/3, CIN3; High-Risk HPV; precancer 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: HPV-EU-001