Long Term Immunogenicity Study of Engerix-B Vaccine in 10 Year Old Children and the Effect of Booster Injections

Open Randomised Clinical Study of the Long Term Immunogenicity of Engerix-B in 10 Year Old Children and of the Effect of Booster Injections Given 5, 10 or 15 Years After Primary Vaccination

Hepatitis B immunization has been offered to all grade 4 students (age 9-10) in the province of Quebec, using Engerix-B at a dose of 10 mkg. The peak incidence of hepatitis B occurs between age 15 and 35; the proportion of vaccinated children who will still be protected at this age is currently unknown. This study is designed to determine:

• persistence of immunity until age 25
• persistence of immunological memory as demonstrated by an anamnestic response following a booster dose
• the effect of a booster dose on immunogenicity at either 5, 10 or 15 years after the primary vaccination course (at age (15, 20 or 25).

Study Overview

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

Detailed Description

Three doses of Engerix-B vaccine (10 mkg) were administered according to 0, 1, 6 month schedule to 1126 9-10 year-old children.

The primary objective of the study is to evaluate the persistence of antibodies to Engerix-B in all subjects at age 25 and to compare the levels obtained in those given a booster injection at age 15 or 20 with those receiving no booster injection.

Secondary objectives

• To determine the antibody levels obtained following primary vaccination and the proportion of children who seroconvert
• To determine the antibody levels of one third of subjects at age 15, 5 years after primary vaccination (Group A)
• To determine the effect on antibody levels of a booster injection at age 15 years given to one third of the subjects (Group A)
• To determine the antibody levels of subjects in groups A and B at age 20, 5 years after booster (Group A), 10 years after primary vaccination (Group B)
• To determine the effect on antibody levels of a booster injection at age 20 years given to one third of the subjects (Group B)
• To determine the effect on antibody levels of a booster injection at age 25 years given to one third of the subjects (Group C)
• To determine the antibody levels of subjects in Group A and Group B one year after their 5 or 10 year booster
• To evaluate safety

• Study Type: Interventional
• Enrollment (Actual): 1129
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1E 7G9
    • Vladimir Gilca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 10 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Previously completed the 1995 to 1996 Hepatitis B vaccination program vaccinations (Primary study) to the best of his/her knowledge and already enrolled and followed in the long term study
• Must be HBc negative
• Required standard interval between last dose of primary immunization and booster vaccination
• Written informed consent obtained from the subject
• Free of obvious health problems as established by medical history and clinical examination before entering into the study
• Previously completed routine childhood vaccination to the best of his/her knowledge
• If the subject is female, and the potential of pregnancy exists, it must be asked prior to immunization by the study nurse. According to the protocol d'immunisation du Québec, Engerix-B is not contra-indicated during pregnancy. However, if a participant thinks she could be pregnant (sexually active and no oral contraception or intra uterine device), a pregnancy test will be carried out. In case of pregnancy, the booster vaccination will be performed after delivery.

Exclusion Criteria:

- Not applicable

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the persistence of antibodies to Engerix-B in all subjects at age 25 and to compare the levels obtained in those given a booster injection at age 15 or 20 with those receiving no booster injection.	Long term persistence of anti-HBs and the effect of a booster dose given 5, 10 or 15 years post-primary vaccination.	1995 - 2011

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
- To determine the antibody levels obtained following primary vaccination and the proportion of children who seroconvert	Anti-HBs titers were measured 1 months post-primary vaccination	1 month post primary vaccination
- To determine the antibody levels of one third of subjects at age 15, 5 years after primary vaccination (Group A)	Anti-HBs titers were measured 5 years post primary vaccination.	2001
- To determine the effect on antibody levels of a booster injection at age 15 years given to one third of the subjects (Group A)	The effect of a booster dose was measured	2001
- To determine the antibody levels of subjects in groups A and B at age 20, 5 years after booster (Group A), 10 years after primary vaccination (Group B)	Anti-HBs titers were measured 10 years post primary vaccination (Group B) and 5 years post booster dose (Group A)	2006
- To determine the effect on antibody levels of a booster injection at age 20 years given to one third of the subjects (Group B)	Anti-HBs titers were measured 1 month post booster dose given 10 years post-primary vaccination	2006
- To determine the persistence of antibody 15 years after primary vaccination (Group C)	Anti-HBs titers will be measured	2011
- To determine the antibody levels of subjects in Group A and Group B one year after their 5 or 10 year booster	anti-HBs titers will be measured 10 years post booster dose (Group A) and 5 years post booster dose (Group B)	2011
- To evaluate the effect of a booster dose given 15 years post primary vaccination (Group C)	Anti-HBs titers will be measured one month post booster dose (Group C)	2011

Collaborators and Investigators

• Sponsor: Laval University
• Collaborators: Institut National en Santé Publique du Québec; Centre de Recheche du Centre Hospitalier Université Laval; SmithKlinBeecham Biologicals
• Investigators: Principal Investigator: Bernard Duval, MD, Laval University Hospital Center, Public Health Research Unit

Publications and helpful links

General Publications

• Duval B, Gilca V, Boulianne N, De Wals P, Masse R, Trudeau G, De Serres G. Comparative long term immunogenicity of two recombinant hepatitis B vaccines and the effect of a booster dose given after five years in a low endemicity country. Pediatr Infect Dis J. 2005 Mar;24(3):213-8. doi: 10.1097/01.inf.0000154329.00361.39.
• Duval B, Boulianne N, De Serres G, Laflamme N, De Wals P, Masse R, Trudeau G, Delage G, Desjardins L. Comparative immunogenicity under field conditions of two recombinant hepatitis B vaccines in 8-10-year-old children. Vaccine. 2000 Feb 14;18(15):1467-72. doi: 10.1016/s0264-410x(99)00422-3.
• Gilca V, De Serres G, Boulianne N, De Wals P, Murphy D, Trudeau G, Masse R, Duval B. Antibody kinetics among 8-10 years old respondents to hepatitis B vaccination in a low endemic country and the effect of a booster dose given 5 or 10 years later. Vaccine. 2009 Oct 9;27(43):6048-53. doi: 10.1016/j.vaccine.2009.07.100. Epub 2009 Aug 13.
• Gilca V, De Serres G, Boulianne N, Murphy D, De Wals P, Ouakki M, Trudeau G, Masse R, Dionne M. Antibody persistence and the effect of a booster dose given 5, 10 or 15 years after vaccinating preadolescents with a recombinant hepatitis B vaccine. Vaccine. 2013 Jan 7;31(3):448-51. doi: 10.1016/j.vaccine.2012.11.037. Epub 2012 Dec 1.

Study record dates

Study Major Dates

• Study Start: September 1, 1995
• Primary Completion (ACTUAL): October 1, 2011
• Study Completion (ACTUAL): May 1, 2012

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (ESTIMATE): September 15, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): May 29, 2013
• Last Update Submitted That Met QC Criteria: May 24, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Vaccination; Hepatitis B; Engerix-B; Booster dose; Long-term immunity
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis
• Other Study ID Numbers: HBV-257 ext. HBV-278; 103860/257 ext. 278