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

Phase 1

Completed

• Conditions: Hepatitis B, Chronic
• Interventions: Genetic: HB-110

• Registration Number: NCT01641536
• Lead Sponsor: Genexine, Inc.

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.

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2012-06-28
• Study First Submitted QC: 2012-07-12
• Study First Posted: 2012-07-16
• Primary Completion: 2012-12
• Study Completion: 2013-04
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-19
• Last Update Posted: 2013-06-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1mg of HB-110	HB-110	The subjects in this group will be administered 1 mg of HB-110 according to the protocol.
2mg of HB-110	HB-110	The subjects in this group will be administered 2 mg of HB-110 according to the protocol.
4mg of HB-110	HB-110	The subjects in this group will be administered 4 mg of HB-110 according to the protocol.

Primary Outcome Measures

Name	Time	Method
Frequency of Adverse Events	1 year
Degree of Adverse Events	1 year

Secondary Outcome Measures

Name	Time	Method
Level of HBV antigen-specific T-cell ex-vivo ELISPOT	1 year
Level of HBV antigen-specific T-cell cultured ELISPOT	1 year
Maintenance of HBeAg seroconversion if they had HBeAg seroconversion at Screening Visit, otherwise occurence of HBeAg seroconversion at Follow-up Visit	1 year
HBsAg loss and HBsAg seroconversion rate at Follow-up Visit	1 year
ALT level	1 year
level of HBsAg titer	1 year
Number of HBV DNA Copies	1 year

Trial Locations

Locations (1)

Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of