Clinical trial NCT01817725: Hepatitis B Vaccine in Chronic Hepatitis B Patients With Low Serum HBsAg
Official title: Effect of Hepatitis B Vaccine in Chronic Hepatitis B Patients With Low Serum HBsAg-a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Hepatitis B
Keywords: Therapeutic vaccine
HBsAg clearance
Immune clearance
HBsAg clearance induced by vaccination
s seroconversion in carriers after vaccination
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2013-03-25
Enrollment: 20
Sex: ALL
Minimum age (years): 3
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in HBsAg Levels From Baseline to 2 Years
timeFrame: 2 years
Secondary outcomes:
measure: Anti-HBs Seropositivity
timeFrame: 2 years
Other outcomes:
Locations:
city: Taoyuan Xian
country: Taiwan
facility: Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Ming-Wei Lai
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: Chao-Wei Hsu
role: PRINCIPAL_INVESTIGATOR
affiliation: Chang Gung Memorial Hospital
name: Chau-Ting Yeh
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.