Clinical trial NCT00875485: Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™
Official title: An Open Multicentre, Multicountry Study to Evaluate Long-term Antibody Persistence and Immune Memory Between Years 11 and 15 After the Primary Study HAB-084 in Which Healthy Adolescents Were Vaccinated With Twinrix™ Adult Following a Two-dose Schedule or Twinrix™ Junior Following a Three-dose Schedule.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hepatitis B
Hepatitis A
Keywords: Monovalent Hepatitis A
hepatitis B vaccine
Belgium and Czech Republic
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-04-03
Enrollment: 210
Sex: ALL
Minimum age (years): 12
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study will evaluate the immune response against Hepatitis-A (HAV) and Hepatitis B surface (HBs) antigen in healthy subjects aged 12 to 15 years (at the time of primary vaccination), who received vaccination course with GSK Biologicals' Twinrix Adult and Twinrix Junior vaccine, approximately 10 years ago in the primary study. The subjects will be invited for blood sampling at 11, 12, 13, 14 and 15 years after primary vaccination to evaluate the persistence of immune response. For subjects detected with decreased immunity, the presence of immune memory against hepatitis A \& B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine 6 to 12 months after the Year 15 follow-up time-point.

No new subjects will be recruited during this booster phase of the study.


Eligibility criteria: 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 who received the complete primary vaccination course according to his/her group allocation in the primary study
* Written informed consent obtained from the subject.

All subjects must satisfy the following criteria at entry into the challenge dose phase:

* A male or female who received the complete primary vaccination course according to his/her group allocation in the primary study.
* Subjects who participated in the long-term follow-up phase of the primary study and for whom the antibody concentrations were below specified value for anti-HAV antibodies and/ or for anti-HBs antibodies at the last available follow-up time-points.
* Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study.
* Written informed consent obtained from the subject.
* Healthy subjects as established by medical history and clinical examination before entering into the challenge dose phase of this study.
* If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.

Exclusion Criteria:

The following criteria should be checked at each follow-up visit. If any apply at study entry, the subject must not be included at that long-term follow-up visit.

* Use of any investigational or non-registered product (drug or vaccine) since the last blood sampling visit.
* Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine since the primary vaccination course of the primary study.
* History of hepatitis A or hepatitis B infection.
* Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within 3 months prior to blood sampling.

The following criteria should be checked before the challenge dose phase. If any apply, the subject must not be included in the challenge dose phase:

* Use of any investigational or non-registered product (drug or vaccine) within 30 days before the administration of the challenge dose or planned use during the study period outside the context of the study.
* Administration of a hepatitis A, hepatitis B or hepatitis combination vaccine between the primary vaccination course of the primary study and the challenge dose visit.
* History of hepatitis A or hepatitis B infection.
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* History of allergic disease or reactions likely to be exacerbated by any component of the vaccines.
* Acute disease at the time of.
* Administration of immunoglobulins and/or any blood products within the three months preceding the administration of the challenge dose or planned administration before the final blood sampling point (one month after the challenge dose).
* Pregnant or lactating female.

Primary outcomes:
measure: Anti-HAV Antibody Concentrations
timeFrame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084
measure: Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values
timeFrame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084
measure: Anti-HBs Antibody Concentrations
timeFrame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084.
measure: Anti-HBs Anamnestic Response.
timeFrame: One month after the challenge dose.
measure: Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.
timeFrame: At Year 11, 12, 13, 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084.
Secondary outcomes:
measure: Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
timeFrame: Since the last long-term follow-up visit up to Year 11.
measure: Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
timeFrame: Since the last long-term follow-up visit up to Year 12.
measure: Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
timeFrame: Since the last long-term follow-up visit up to Year 13.
measure: Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
timeFrame: Since the last long-term follow-up visit up to Year 14.
measure: Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.
timeFrame: Since the last long-term follow-up visit up to Year 15.
measure: Number of Subjects With Anti-hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-off Value.
timeFrame: Before (PRE) the challenge dose
measure: Anti-HAV Antibody Concentrations
timeFrame: Before (PRE) the challenge dose
measure: Number of Subjects Reporting Any and Grade 3 Solicited Local Adverse Events.
timeFrame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose
measure: Number of Subjects With Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-off Values
timeFrame: Before (PRE) and one month after (POST) the challenge dose
measure: Anti-HBs Antibody Concentrations
timeFrame: Before (PRE) and one month after (POST) the challenge dose
measure: Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms.
timeFrame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose.
measure: Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Symptoms.
timeFrame: During the 31-day (Day 0 to 30) follow-up period after the challenge dose.
measure: Number of Subjects With Serious Adverse Events (SAEs).
timeFrame: One month after the administration of the challenge dose (Month 0 to Month 1)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Hradec Kralove
country: Czechia
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Agrawal A, Kolhapure S, Andani A, Ota MOC, Badur S, Karkada N, Mitra M. Long-Term Persistence of Antibody Response with Two Doses of Inactivated Hepatitis A Vaccine in Children. Infect Dis Ther. 2020 Dec;9(4):785-796. doi: 10.1007/s40121-020-00311-8. Epub 2020 Jul 24.
citation: Beran J, Van Der Meeren O, Leyssen M, D'silva P. Immunity to hepatitis A and B persists for at least 15 years after immunisation of adolescents with a combined hepatitis A and B vaccine. Vaccine. 2016 May 23;34(24):2686-91. doi: 10.1016/j.vaccine.2016.04.033. Epub 2016 Apr 20.