Safety and Immunogenicity of a Booster Dose of GlaxoSmithKline (GSK) Biologicals' Hepatitis B Vaccine

Immune Response to a Hepatitis B Vaccine Challenge Dose in Healthy Subjects Who Received Primary Vaccination of GlaxoSmithKline Biologicals' Hepatitis B Vaccine, Approximately 20 Years Ago.

In this study, subjects who received primary neonatal vaccination with hepatitis B vaccine at 0, 1, 2, 12 months, 20 years ago in the 103860/272 primary study will be evaluated for immunological memory to hepatitis B vaccine via assessment of the response to a vaccine challenge dose.

Study Overview

• Status: Completed
• Conditions: Hepatitis B
• Intervention / Treatment: Biological: Engerix™-B

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
• A male or female adult who received the complete neonatal primary vaccination course of hepatitis B vaccine (Engerix™-B), in the 103860/272 primary study approximately 20 years earlier.
• Documented level of anti-HBs antibody concentrations < 100 milli-international units per milliliter (mIU/ml) at the previous long-term time-point for which serological results are available for that subject.
• Written informed consent obtained from the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the hepatitis B challenge dose.

Exclusion Criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the hepatitis B vaccine challenge dose.
• Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before the hepatitis B vaccine challenge dose and ending 30 days after.
• Subjects who received a booster dose of hepatitis B vaccine outside the context of this study between the long-term time-point at the documented level of anti-HBs antibody concentrations and the current challenge dose study visit.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• Acute disease at the time of enrolment.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Administration of immunoglobulins and/or any blood products within the three months preceding the hepatitis B vaccine challenge dose or planned administration during the study period.
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue contraceptive precautions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Neonates from mother HBsAg (+) and HBeAg (+) had received HBV vaccine at Month 0, 1, 2, 12, 60 (5 doses)	Biological: Engerix™-B; A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.
Experimental: Group 2; Neonates from mother HBsAg (+) and HBeAg (+) had received HBV vaccine at Month 0, 1, 2, 12 (4 doses)	Biological: Engerix™-B; A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.
Experimental: Group 4; Neonates from mother HBsAg (+) and HBeAg (-) had received HBV vaccine at Month 0, 1, 2, 12 (4 doses)	Biological: Engerix™-B; A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.
Experimental: Group 6; Neonates from mother HBsAg (-) and HBeAg (-) had received HBV vaccine at Month 0, 1, 2, 12 (4 doses)	Biological: Engerix™-B; A challenge dose of hepatitis B vaccine will be administered to all subjects as a deep intramuscular injection in the deltoid region of the non-dominant arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With an Immune Response to a Challenge Dose of Hepatitis B Vaccine	Immune response to a challenge dose of hepatitis B vaccine is defined as; at least a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive (≥ 3.3 mIU/mL) at the previous available long-term time point, or; a post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in subjects seronegative (<3.3 mIU/mL) at the previous available long-term time point.	One month after the hepatitis B vaccine challenge dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Anti-HBs Antibody Concentrations Above Pre-defined Cut-off Values	Anti-hepatitis B surface antigen (anti-HBs) antibody cut-off values assessed include 3.3, 10 and 100 mIU/mL.	One month after the hepatitis B vaccine challenge dose
Concentration of Anti-HBs Antibodies	Concentrations are given as Geometric Mean Concentrations (GMCs), calculated on subjects seropositive (subjects with anti-HBs antibody concentrations ≥ 3.3 mIU/mL) post-challenge dose.	One month after the hepatitis B vaccine challenge dose
Number of Subjects Reporting Unsolicited Adverse Events	An adverse event is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.	During the 31-day follow-up period after the challenge dose of hepatitis B vaccine
Number of Subjects Reporting Serious Adverse Events	A serious adverse event is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.	During the 31-day follow-up period after the challenge dose of hepatitis B vaccine

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Poovorawan Y et al. Persistence of anti-HBs antibodies and immune memory 20-years after hepatitis B vaccination among children in Thailand. Abstract presented at the 9th International Congress of Tropical Pediatrics (ICTP). Bangkok, Thailand. 18-20 October 2011.
• Poovorawan Y, Chongsrisawat V, Theamboonlers A, Crasta PD, Messier M, Hardt K. Long-term anti-HBs antibody persistence following infant vaccination against hepatitis B and evaluation of anamnestic response: a 20-year follow-up study in Thailand. Hum Vaccin Immunother. 2013 Aug;9(8):1679-84. doi: 10.4161/hv.24844. Epub 2013 May 31.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: April 8, 2008
• First Submitted That Met QC Criteria: April 11, 2008
• First Posted (Estimate): April 14, 2008

Study Record Updates

• Last Update Posted (Estimate): December 21, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: vaccine; Hepatitis
• 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
• Other Study ID Numbers: 110071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: 110071
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 110071
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 110071
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 110071
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 110071
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 110071
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register