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

NCT ID: NCT01817725

Last Updated: 2017-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2016-02-29

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

HBV vaccine (Engerix B)

Intervention Type: BIOLOGICAL

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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Ming-Wei Lai

M.D., Ph.D.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ming-Wei Lai

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Chao-Wei Hsu

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Chau-Ting Yeh

Role: PRINCIPAL_INVESTIGATOR

Chang Gung Memorial Hospital

Locations

Chang Gung Memorial Hospital

Taoyuan Xian, , Taiwan

Countries

Taiwan

References

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.

Reference Type: DERIVED

PMID: 30088198 (View on PubMed)

Other Identifiers

ChangGungMH 101-3594A3

Identifier Type: -

Identifier Source: org_study_id