Hepatitis B Vaccine in Chronic Hepatitis B Patients With Low Serum HBsAg

Effect of Hepatitis B Vaccine in Chronic Hepatitis B Patients With Low Serum HBsAg-a Pilot Study

Background:

The HBsAg clearance rate in interferon-treated responders is significantly higher than that in lamivudine-treated responders, implying immune control is the key to HBsAg clearance. There is a good chance to further increase the cure rate if the investigators can enhance the HBV-specific immune response when the HBsAg level already comes to a low level.

Hypothesis: HBsAg-based vaccine can enhance HBsAg clearance in chronic hepatitis B patients whose HBsAg already <=2000 IU/ml.

Patients and methods:

This pilot study will enroll 20 chronic hepatitis B patients with HBsAg ≦2000 IU/ml, no hepatic decompensation, no HIV coinfection, nor clinical immunodeficiency. Engerix-B vaccine (20μg for <20 years old and 40 μg for ≥ 20 years old) will be given every 2 months for one year. HBsAg quantification, anti-HBs, and HBV DNA will be surveyed regularly before each dose during the treatment period and every 3 months for another year following the last dose. Viral and cellular factors will be studied to discover determinants affecting HBsAg clearance.

Aims

1. To elucidate whether HBsAg-based vaccine can reactivate host immunity to eliminate chronic HBV infection in patients with low titer HBsAg.
2. To delineate the doses to response (HBsAg clearance or decline rate) correlation so as to design a feasible schedule for future clinical trials in a larger group of patients.
3. To discover viral and host factors which can be used as biomarkers for personalized vaccine therapy.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: HBV vaccine (Engerix B)

Detailed Description

Vaccination schedule:

Engerix-B (20μg/ml, GlaxoSmithKline Biologicals) will be administered intramuscularly at 0, 2, 4, 6, 8, 10, 12 months or until HBsAg clearance. The dosage will be 20μg in those <= 20 years old and 40μg in those > 20 years old.

HBsAg and anti-HBs:

qHBsAg will be checked by commercial kits (Elecsys, Roche Diagnostics, Indianapolis, IN) at baseline, right before every dose, and every 3 months following the last dose for one year. ALT, AST, Alpha-fetoprotein, bilirubin and anti-HBs will be checked simultaneously.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• Taiwan
  • Taoyuan Xian, Taiwan, 33305
    • Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Naïve or treated chronic hepatitis B patients with positive HBsAg and negative HBeAg;
2. Quantitative serum HBsAg (qHBsAg) <2000 IU/ml;
3. No HIV co-infection;
4. No obvious immunodeficiency (such as renal failure, chemotherapy, radiotherapy, immunosuppressant);
5. Aged 3 to 80 years;

Exclusion Criteria:

1. Pregnancy
2. Allergic to HBV vaccine or yeast.
3. Hepatic decompensation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Engerix-B; Engerix-B (20 μg/ml, GlaxoSmithKline) was administered at 0-2-4-6-8-10-12 months in dosage of 40μg for >20 years old and 20μg for < or =20 years old	Biological: HBV vaccine (Engerix B); Engerix-B (20μg/ml, GlaxoSmithKline Biologicals) is administered intramuscularly at 0, 2, 4, 6, 8, 10, 12 months. The dosage will be 20μg in those <= 20 years old and 40μg in those > 20 years old.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HBsAg Levels From Baseline to 2 Years	The difference of HBsAg levels at the end of follow up (2 years) and baseline	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Anti-HBs Seropositivity	2 years

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Ming-Wei Lai, Chang Gung Memorial Hospital; Principal Investigator: Chao-Wei Hsu, Chang Gung Memorial Hospital; Principal Investigator: Chau-Ting Yeh, Chang Gung Memorial Hospital

Publications and helpful links

General Publications

• Lai MW, Hsu CW, Lin CL, Chien RN, Lin WR, Chang CS, Liang KH, Yeh CT. Multiple doses of hepatitis B recombinant vaccine for chronic hepatitis B patients with low surface antigen levels: a pilot study. Hepatol Int. 2018 Sep;12(5):456-464. doi: 10.1007/s12072-018-9890-x. Epub 2018 Aug 7.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: March 21, 2013
• First Submitted That Met QC Criteria: March 22, 2013
• First Posted (Estimate): March 25, 2013

Study Record Updates

• Last Update Posted (Actual): May 2, 2017
• Last Update Submitted That Met QC Criteria: March 22, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Therapeutic vaccine; HBsAg clearance; Immune clearance; HBsAg clearance induced by vaccination; s seroconversion in carriers after vaccination
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: ChangGungMH 101-3594A3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO