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Tolerability, Immunogenicity and Efficacy of HB-110 Administered by Electroporation in Chronic Hepatitis B Patients

Primary Purpose

Hepatitis B, Chronic

Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
HB-110
Sponsored by
Genexine, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic focused on measuring Hepatitis, Chronic, Virus Diseases, DNA Virus Infections, Hepatitis B, Liver, Chronic Disease, HBV

Eligibility Criteria

20 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Agreed that female subjects or female partners of male subjects will not be pregnant during the study.
  • Chronic hepatitis B patients who are taking Entecavir at the Screening Visit for 6 months or longer
  • Have not used IFN alpha or antiviral drugs within the previous 6 months for treating hepatitis.
  • Have blood HBV DNA level of ≤300 copies/mL determined at Screening Visit
  • Have an ALT level less than or equal to 2 times the upper limit of normal [ULN] at the Screening Visit
  • Provide a signed voluntary written informed consent for study participation

Exclusion Criteria:

  • Who have participated in other studies within previous 30 days from Screening Visit

  • Have the following decompensated liver parameters,

    • serum albumin level <3 g/dL,
    • total bilirubin level >2.5 mg/dL,
    • international normalized ratio (INR) >1.8
  • Do not have adequate renal function as determined by serum creatinine level 1.5 times more than normal range(1.2 mg/dL)
  • Had a previous liver transplant or bone marrow transplant
  • Are currently taking immunosuppressive or possible immunomodulatory drugs
  • Women who are pregnant or breastfeeding
  • female subjects will be pregnant or breastfeed during the study
  • History of allergy/hypersensitivity to drugs
  • Any clinically significant acute or chronic unstable renal, cardiac or endocrine disease (e.g., cardiac failure, renal failure, pancreatitis, diabetes mellitus)
  • Presence of any other primary or secondary hepatic disease (e.g., hemochromatosis, Wilson's disease, alcoholic hepatic disease, non alcoholic fatty liver, alpha-1-antitrypsin deficiency and so on) other than hepatitis B
  • Who were observed for hepatocellular mass by ultrasonography and have an abnormal increase of serum AFP
  • Past or present history of hepatocarcinoma
  • History of grand mal epilepsy, or currently on anti-epileptic medications
  • Occurrence of at least one episode of syncope within the last 12 months
  • Presence of an implantable cardiac device (pacemaker, automated implantable cardioverter defibrillator [AICD]) or implantable nerve stimulator
  • Who have arrhythmia
  • Any other conditions that are considered inappropriate for the study by the Investigator.

Sites / Locations

  • Seoul St. Mary's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

1mg of HB-110

2mg of HB-110

4mg of HB-110

Arm Description

The subjects in this group will be administered 1 mg of HB-110 according to the protocol.

The subjects in this group will be administered 2 mg of HB-110 according to the protocol.

The subjects in this group will be administered 4 mg of HB-110 according to the protocol.

Outcomes

Primary Outcome Measures

Frequency of Adverse Events
Degree of Adverse Events

Secondary Outcome Measures

Level of HBV antigen-specific T-cell ex-vivo ELISPOT
Level of HBV antigen-specific T-cell cultured ELISPOT
Maintenance of HBeAg seroconversion if they had HBeAg seroconversion at Screening Visit, otherwise occurence of HBeAg seroconversion at Follow-up Visit
HBsAg loss and HBsAg seroconversion rate at Follow-up Visit
ALT level
level of HBsAg titer
Number of HBV DNA Copies

Full Information

First Posted
June 28, 2012
Last Updated
June 19, 2013
Sponsor
Genexine, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01641536
Brief Title
Tolerability, Immunogenicity and Efficacy of HB-110 Administered by Electroporation in Chronic Hepatitis B Patients
Official Title
An Open-label, Dose-escalating Clinical Study to Evaluate the Tolerability, Immunogenicity and Efficacy of HB-110 Administered by Electroporation (EP) in an Add-on Therapy With Entecavir in Chronic Hepatitis B Patients
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genexine, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is an open label, dose escalation study using the classical 3+3 design to determine the MTD of HB-110 and assess the safety, immunogenicity and efficacy of HB-110 DNA therapeutic vaccine administered by Electroporation in combination with Entecavir in chronic hepatitis B patients.
Detailed Description
The patients enrolled in the trial will be successively allocated into three cohorts for HB-110 1mg, 2mg, and 4mg in combination with Entecavir according to the classical 3+3 protocol design. They will be administered by Electroporation device. The scheduled assessments and visits will be carried out over three periods: run-in period, treatment period, and follow-up period. The run-in period includes the screening visit where a written informed consent is obtained and the screening period where patients are assessed for eligibility. It will be completed within 14 days prior to Visit 1. The patients meeting inclusion criteria will start the treatment period. During the treatment period, subjects will be administered HB-110 by Electroporation at each visit in combination with antiviral drug, Entecavir. The Follow-up period starts once subjects complete the treatment period and will continue until the follow-up visit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
Keywords
Hepatitis, Chronic, Virus Diseases, DNA Virus Infections, Hepatitis B, Liver, Chronic Disease, HBV

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1mg of HB-110
Arm Type
Experimental
Arm Description
The subjects in this group will be administered 1 mg of HB-110 according to the protocol.
Arm Title
2mg of HB-110
Arm Type
Experimental
Arm Description
The subjects in this group will be administered 2 mg of HB-110 according to the protocol.
Arm Title
4mg of HB-110
Arm Type
Experimental
Arm Description
The subjects in this group will be administered 4 mg of HB-110 according to the protocol.
Intervention Type
Genetic
Intervention Name(s)
HB-110
Other Intervention Name(s)
Baraclude(Entecavir), TriGrid™ Delivery System
Intervention Description
Each patient will be administered HB-110 by Electroporation for 20 weeks based on the protocol and take one pill of Entecavir(0.5 mg) per day during the study period. The Dose of HB-110 will be determined by the classical 3+3 dose escalation schedule and dose levels are 1mg, 2mg, 4mg respectively. The number of patients will be ranged from 9 to 18.
Primary Outcome Measure Information:
Title
Frequency of Adverse Events
Time Frame
1 year
Title
Degree of Adverse Events
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Level of HBV antigen-specific T-cell ex-vivo ELISPOT
Time Frame
1 year
Title
Level of HBV antigen-specific T-cell cultured ELISPOT
Time Frame
1 year
Title
Maintenance of HBeAg seroconversion if they had HBeAg seroconversion at Screening Visit, otherwise occurence of HBeAg seroconversion at Follow-up Visit
Time Frame
1 year
Title
HBsAg loss and HBsAg seroconversion rate at Follow-up Visit
Time Frame
1 year
Title
ALT level
Time Frame
1 year
Title
level of HBsAg titer
Time Frame
1 year
Title
Number of HBV DNA Copies
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Agreed that female subjects or female partners of male subjects will not be pregnant during the study. Chronic hepatitis B patients who are taking Entecavir at the Screening Visit for 6 months or longer Have not used IFN alpha or antiviral drugs within the previous 6 months for treating hepatitis. Have blood HBV DNA level of ≤300 copies/mL determined at Screening Visit Have an ALT level less than or equal to 2 times the upper limit of normal [ULN] at the Screening Visit Provide a signed voluntary written informed consent for study participation Exclusion Criteria: Who have participated in other studies within previous 30 days from Screening Visit Have the following decompensated liver parameters, serum albumin level <3 g/dL, total bilirubin level >2.5 mg/dL, international normalized ratio (INR) >1.8 Do not have adequate renal function as determined by serum creatinine level 1.5 times more than normal range(1.2 mg/dL) Had a previous liver transplant or bone marrow transplant Are currently taking immunosuppressive or possible immunomodulatory drugs Women who are pregnant or breastfeeding female subjects will be pregnant or breastfeed during the study History of allergy/hypersensitivity to drugs Any clinically significant acute or chronic unstable renal, cardiac or endocrine disease (e.g., cardiac failure, renal failure, pancreatitis, diabetes mellitus) Presence of any other primary or secondary hepatic disease (e.g., hemochromatosis, Wilson's disease, alcoholic hepatic disease, non alcoholic fatty liver, alpha-1-antitrypsin deficiency and so on) other than hepatitis B Who were observed for hepatocellular mass by ultrasonography and have an abnormal increase of serum AFP Past or present history of hepatocarcinoma History of grand mal epilepsy, or currently on anti-epileptic medications Occurrence of at least one episode of syncope within the last 12 months Presence of an implantable cardiac device (pacemaker, automated implantable cardioverter defibrillator [AICD]) or implantable nerve stimulator Who have arrhythmia Any other conditions that are considered inappropriate for the study by the Investigator.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Seung-Kew Yoon, M.D.
Organizational Affiliation
The Department of Gastroenterology at Seoul St. Mary's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul St. Mary's Hospital
City
Seoul
ZIP/Postal Code
137-701
Country
Korea, Republic of

12. IPD Sharing Statement

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Tolerability, Immunogenicity and Efficacy of HB-110 Administered by Electroporation in Chronic Hepatitis B Patients

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