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

Phase 1

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Biological: HBV vaccine (Engerix B)

• Registration Number: NCT01817725
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

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.

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 Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-21
• Study First Submitted QC: 2013-03-22
• Study First Posted: 2013-03-25
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Results First Submitted: 2017-02-02
• Status Verified: 2017-03
• Results First Submitted QC: 2017-03-22
• Last Update Submitted: 2017-03-22
• Results First Posted: 2017-05-02
• Last Update Posted: 2017-05-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Engerix-B	HBV vaccine (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

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Anti-HBs Seropositivity	2 years

Trial Locations

Locations (1)

Chang Gung Memorial Hospital; 🇨🇳 Taoyuan Xian, Taiwan