Evaluation of Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™

NCT00875485 | Completed Phase 4 Results

• 6 other identifiers: 110699110700110701110702110703110704
• Study Type: interventional
• Target: 210
• Locations: 2 countries
• Sites: 2

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.

Conditions

Hepatitis B; Hepatitis A

Keywords

Monovalent Hepatitis A; hepatitis B vaccine; Belgium and Czech Republic

Outcome Measures

Primary Outcomes (5)

• Anti-HAV Antibody Concentrations

  Antibody concentrations are expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HAV seropositive subjects. Seropositive subjects are subjects with anti-HAV antibody concentrations \>= 15 mIU/mL.

  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

• Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values

  Anti-HBs antibody cut-off values assessed were \>= 6.2 mIU/mL and \>= 10 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by ChemiLuminescence ImmunoAssay (CLIA).

  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

• Anti-HBs Antibody Concentrations

  Antibodys concentrations are expressed as Geometric Mean concentrations (GMCs) in mIU/mL. The analysis was performed on anti-HBs seropositive subjects. Seropositive subjects are subjects with anti-HBs antibody concentrations \>= 6.2 mIU/mL. Note: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 11 to 13. Results of year 14 and year 15 were only analysed by CLIA.

  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.

• Anti-HBs Anamnestic Response.

  Anamnestic response was defined as: Anti-HBs antibody concentrations ≥ 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time-points. At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time-points.

  One month after the challenge dose.

• Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value.

  Anti-HAV antibody cut-off value assessed was \>= 15 milli-International Units per milliliter (mIU/mL).

  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 (13)

• Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.

  Since the last long-term follow-up visit up to Year 11.

• Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.

  Since the last long-term follow-up visit up to Year 12.

• Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.

  Since the last long-term follow-up visit up to Year 13.

• Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.

  Since the last long-term follow-up visit up to Year 14.

• Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection.

  Since the last long-term follow-up visit up to Year 15.

Study Arms (2)

Twinrix Adult Group

EXPERIMENTAL

Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study

Procedure: Blood sampling; Biological: Additional challenge dose

Twinrix Junior Group

EXPERIMENTAL

Subjects received 3 doses of Twinrix™ Junior (= half dose Twinrix™ Adult) intramuscularly according to a 0, 1, 6 month schedule in the primary study

Procedure: Blood sampling; Biological: Additional challenge dose

Interventions

Blood sampling PROCEDURE

Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.

Twinrix Adult Group; Twinrix Junior Group

Additional challenge dose BIOLOGICAL

If a subject became seronegative for anti-HAV antibodies (\< 15 mIU/mL) or if anti-HBs antibody concentrations decreased below 10 mIU/mL during the long-term follow-up, immune memory against the antigen was evaluated by administering a challenge dose of the appropriate antigen (vaccine) 6 to 12 months after the Year 15 follow-up time-point.

Twinrix Adult Group; Twinrix Junior Group

Eligibility Criteria

• Age: 12 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Brussels, 1200, Belgium

Location

GSK Investigational Site

Hradec Králové, 500 03, Czechia

Location

Related Publications (2)

• 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.

  PMID: 32710245 DERIVED

• 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.

  PMID: 27105563 DERIVED

Related 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.

MeSH Terms

Conditions

Hepatitis B; Hepatitis A

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL).The table shows updated results following complete retesting and reanalysis.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2009
• First Posted: April 3, 2009
• Study Start: May 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: August 20, 2018
• Results First Posted: July 5, 2010

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share

Locations

BE (1); CZ (1)