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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00875485
First received: April 2, 2009
Last updated: January 9, 2014
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Hepatitis B
Hepatitis A
Procedure: Blood sampling
Biological: Additional challenge dose
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Study to Evaluate Antibody Persistence & Immune Memory in Subjects Vaccinated During Adolescence With Twinrix™

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. [ Time Frame: At Year 11, 12 and 13 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084. ] [ Designated as safety issue: No ]

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

    Data were analyzed up to Year 13. Results for the other time points will be disclosed when available.


  • Number of Subjects With Anti-Hepatitis A (HAV) Antibody Concentrations Equal to or Above the Cut-Off Value. [ Time Frame: At Year 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084 ] [ Designated as safety issue: No ]
  • Anti-HAV Antibody Concentrations [ Time Frame: At Year 11, 12 and 13 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084. ] [ Designated as safety issue: No ]

    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.

    Data were analyzed up to Year 13. Results for additional time points will be disclosed when available.


  • Anti-HAV Antibody Concentrations [ Time Frame: At Year 14 and 15 after the first vaccine dose of two-dose or three-dose primary vaccination in study HAB-084 ] [ Designated as safety issue: No ]
    Antibody concentrations will be expressed as Geometric Mean concentrations (GMCs) in mIU/mL.

  • Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values [ Time Frame: At Year 11, 12 and 13 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084 ] [ Designated as safety issue: No ]

    Anti-HBs antibody cut-off values assessed were >= 3.3 mIU/mL and >= 10 mIU/mL.

    Data were analyzed up to Year 13. Results for additional time points will be disclosed when available.


  • Anti-HBs Antibody Concentrations [ Time Frame: At Year 11, 12 and 13 after the first vaccine dose of a two-dose or a three-dose primary vaccination in study HAB-084. ] [ Designated as safety issue: No ]

    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 >= 3.3 mIU/mL.

    Data were analyzed up to Year 13. Results for additional time points will be disclosed when available.


  • Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above the Cut-Off Values [ Time Frame: At Year 14 and 15 after the first vaccine dose of the two-dose or three-dose primary vaccination in study HAB-084 ] [ Designated as safety issue: No ]
  • Anti-HAV Anamnestic Response. [ Time Frame: One month after the challenge dose. ] [ Designated as safety issue: No ]
  • Anti-HBs Antibody Concentrations [ Time Frame: At Year 14 and 15 after the first vaccine dose of two-dose or three dose primary vaccination in study HAB-084. ] [ Designated as safety issue: No ]
    Antibody concentrations will be expressed as Geometric Mean concentrations (GMCs) in mIU/mL

  • Anti-HBs Anamnestic Response. [ Time Frame: One month after the challenge dose. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 11. ] [ Designated as safety issue: No ]
    SAE 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 12. ] [ Designated as safety issue: No ]
    SAE 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 13. ] [ Designated as safety issue: No ]
    SAE 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 14. ] [ Designated as safety issue: No ]
    SAE 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.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) or Hepatitis A or B Infection. [ Time Frame: Since the last long-term follow-up visit up to Year 15. ] [ Designated as safety issue: No ]
    SAE 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.

  • Number of Subjects With Anti-HAV Antibody Concentrations Above or Equal to Specified Value and Geometric Mean Concentrations (GMCs). [ Time Frame: Before and one month after the challenge dose. ] [ Designated as safety issue: No ]
  • Number of Subjects With Anti-HBs Antibody Concentrations Above or Equal to Specified Value and GMCs. [ Time Frame: Before and one month after the challenge dose. ] [ Designated as safety issue: No ]
  • Number of Subjects With Solicited Local Symptoms. [ Time Frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose. ] [ Designated as safety issue: No ]
  • Number of Subjects With Solicited General Symptoms. [ Time Frame: During the 4-day (Day 0 to Day 3) follow-up period after the challenge dose. ] [ Designated as safety issue: No ]
  • Number of Subjects With Unsolicited Symptoms. [ Time Frame: During the 31-day (Day 0 to 30) follow-up period after the challenge dose. ] [ Designated as safety issue: No ]
  • Number of Subjects With Serious Adverse Events [ Time Frame: One month after the administration of the challenge dose. ] [ Designated as safety issue: No ]

Enrollment: 210
Study Start Date: May 2009
Estimated Study Completion Date: March 2014
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Twinrix Adult Group
Subjects received 2 doses of Twinrix™ Adult intramuscularly according to a 0, 6 month schedule in the primary study
Procedure: Blood sampling
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
Biological: Additional challenge dose
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.
Experimental: Twinrix Junior Group
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
Blood sampling at Years 11, 12, 13, 14, 15 and at the time of challenge dose administration and one month after challenge dose administration.
Biological: Additional challenge dose
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.

  Eligibility

Ages Eligible for Study:   12 Years to 15 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00875485

Locations
Belgium
GSK Investigational Site
Bruxelles, Belgium, 1200
Czech Republic
GSK Investigational Site
Hradec Kralove, Czech Republic, 500 03
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00875485     History of Changes
Other Study ID Numbers: 110699, 110700, 110701, 110702, 110703, 110704
Study First Received: April 2, 2009
Results First Received: May 27, 2010
Last Updated: January 9, 2014
Health Authority: Belgium: Direction Générale de la Protection de la Santé Publique Médicaments
Czech: State Institute for Drug Control

Keywords provided by GlaxoSmithKline:
Monovalent Hepatitis A
hepatitis B vaccine
Belgium and Czech Republic

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Antibodies
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014