Antibody Persistence & Immune Memory in Healthy Adults Previously Vaccinated With TwinrixTM Adult

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01000324
First received: October 22, 2009
Last updated: September 4, 2014
Last verified: September 2014
  Purpose

This study will evaluate the persistence of the immune response to HAV (hepatitis A virus) antigens and HBs (hepatitis B surface) antigens in healthy adults previously vaccinated with GSK Biologicals' TwinrixTM Adult. The subjects will be invited for blood sampling 16, 17, 18, 19 and 20 years after vaccination to evaluate the antibody persistence. For subjects in whom low circulating antibodies are detected, the presence of immune memory against hepatitis A & B antigens will be investigated by the administration of a challenge dose of the appropriate vaccine (HavrixTM and/or EngerixTM-B) at the next planned visit.

No new subjects will be recruited during this study.


Condition Intervention Phase
Hepatitis A
Hepatitis B
Procedure: Blood sampling
Biological: EngerixTM-B
Biological: Havrix
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Antibody Persistence and Immune Memory in Healthy Adults Previously Vaccinated With Twinrix™ Adult

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentration Equal to or Above 15 Milli-international Units Per Milliliter (mIU/mL) [ Time Frame: At Year 16 ] [ Designated as safety issue: No ]
    The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study

  • Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentration Equal to or Above 15 Milli-international Units Per Milliliter (mIU/mL) [ Time Frame: At Year 17 ] [ Designated as safety issue: No ]
    The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study

  • Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentration Equal to or Above 15 Milli-international Units Per Milliliter (mIU/mL) [ Time Frame: At Year 18 ] [ Designated as safety issue: No ]
    The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study

  • Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentration Equal to or Above 15 Milli-international Units Per Milliliter (mIU/mL) [ Time Frame: At Year 19 ] [ Designated as safety issue: No ]
    The analysis was performed on LT Total cohort that included all subjects who returned at each annual time point and who belonged to the Total Vaccinated cohort in the primary study

  • Number of Subjects With Anti-hepatitis A (Anti-HAV) Antibody Concentration Equal to or Above 15 Milli-international Units Per Milliliter (mIU/mL) [ Time Frame: At Year 20 ] [ Designated as safety issue: No ]
  • Concentration of Anti-hepatitis A (Anti-HAV) Antibodies [ Time Frame: At Year 16 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis A (Anti-HAV) Antibodies [ Time Frame: At Year 17 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis A (Anti-HAV) Antibodies [ Time Frame: At Year 18 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis A (Anti-HAV) Antibodies [ Time Frame: At Year 19 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis A (Anti-HAV) Antibodies [ Time Frame: At Year 20 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: At Year 16 ] [ Designated as safety issue: No ]
    Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: At Year 17 ] [ Designated as safety issue: No ]
    Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: At Year 18 ] [ Designated as safety issue: No ]
    Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: At Year 19 ] [ Designated as safety issue: No ]
    Anti-HBs antibody cut-off values assessed include 6.2 and 10 milli-international units per milliliter (mIU/mL).

  • Number of Subjects With Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations Equal to or Above the Cut-off Values [ Time Frame: At Year 20 ] [ Designated as safety issue: No ]
    Anti-HBs antibody cut-off values assessed include 3.3 and 10 milli-international units per milliliter (mIU/mL).

  • Concentration of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies [ Time Frame: At Year 16 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies [ Time Frame: At Year 17 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies [ Time Frame: At Year 18 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies [ Time Frame: At Year 19 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).

  • Concentration of Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies [ Time Frame: At Year 20 ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs).


Secondary Outcome Measures:
  • Number of Subjects With Immune Response to the Challenge Vaccine Antigen [ Time Frame: Before, 14 days and one month after the challenge dose at Year 19. ] [ Designated as safety issue: No ]
    None of the subjects received a challenge dose at Years 16, 17 and 18 while, one subject received the challenge dose at Year 19.

  • Number of Subjects With an Anamnestic Response to the Challenge Dose [ Time Frame: One month after the challenge dose at Years 16, 17, 18 and 19 ] [ Designated as safety issue: No ]
    As none of the subjects received a challenge dose at Years 16, 17 and 18. One subject received the challenge dose at Year 19. This secondary outcome variable will be assessed if the final number of subjects (Year 16 to Year 20) receiving a particular challenge dose is greater than 10

  • Anti-hepatitis B Virus (Anti-HBs) Antibody Concentration [ Time Frame: At Year 18, 14 days and 30 days post challenge dose (Year 19) ] [ Designated as safety issue: No ]
    Concentrations are given as Geometric Mean Concentrations (GMCs) expressed as mIU/mL.

  • Number of Subjects Reporting Unsolicited Adverse Events (AE). [ Time Frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Years 16, 17 and 18 ] [ Designated as safety issue: No ]
    As none of the subjects received a challenge dose at Years 16, 17 and 18, the secondary outcome variables described above were not assessed.

  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Years 16, 17 and 18 ] [ Designated as safety issue: No ]
    As none of the subjects received a challenge dose at Years 16, 17 and 18, the secondary outcome variables described above were not assessed.

  • Number of Subjects Reporting Unsolicited Adverse Events (AE). [ Time Frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19. ] [ Designated as safety issue: No ]

    An unsolicited AE was defined as any AE (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

    This secondary outcome variable will be assessed if the final number of subjects (Year 16 to Year 20) receiving a particular challenge dose is greater than 10.


  • Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: During the 31-day (Day 0 to 30) period after administration of the challenge dose at Year 19. ] [ Designated as safety issue: No ]

    A serious adverse event was any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

    This secondary outcome variable will be assessed if the final number of subjects (Year 16 to Year 20) receiving a particular challenge dose is greater than 10.



Enrollment: 40
Study Start Date: November 2009
Study Completion Date: July 2014
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Twinrix Group
Pooled group of subjects from groups who were vaccinated with either Lot 1, Lot 2 or Lot 3 of Twinrix in the primary study according to a 0, 1, 6-Month schedule
Procedure: Blood sampling
Blood sampling at Year 16, 17, 18, 19 and 20 and at the time of challenge dose administration and 14 days and one month after challenge dose administration (if challenge dose needed).
Biological: EngerixTM-B
Engerix-B will be administered to subjects who are not seroprotected against hepatitis B
Biological: Havrix
Havrix will be administered to subjects who are seronegative for anti-HAV antibodies

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All subjects must satisfy the following criteria at entry into each of the long-term follow-up visits:

  • 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 in the primary study HAB-028 (208127/021).
  • Written informed consent obtained from the subject.

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

  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
  • A male or female who received the complete primary vaccination course in the primary study HAB-028 (208127/021).
  • Written informed consent obtained from the subject.
  • Subjects who participated in the long-term follow-up (LTFU) phase of the HAB-028 (208127/021) study and for whom the antibody concentrations were below the cut-off at the last available follow-up time-point.
  • Female subjects of non-childbearing potential may be enrolled in the study.
  • Female subjects of childbearing potential may be enrolled in the study, if the subject:
  • has practiced adequate contraception for 30 days prior to vaccination, and
  • has a negative pregnancy test on the day of vaccination, and
  • has agreed to continue adequate contraception for two months after the administration of the challenge dose.

Exclusion Criteria:

The following criteria should be checked before entry into each of the long-term follow-up visits. If any exclusion criterion applies, the subject must not be included in the study:

  • Use of any investigational or non-registered product within 30 days prior to blood sampling.
  • Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine outside the study procedures, since the primary study HAB-028 (208127/021).
  • History of hepatitis A or hepatitis B infection since the primary study HAB-028 (208127/021).
  • Administration of hepatitis A or hepatitis B immunoglobulins and/or any blood products within three months prior to blood sampling.

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

  • Use of any investigational or non-registered product within 30 days prior to study start or planned use during the study.
  • Administration of a hepatitis A, hepatitis B or combined hepatitis A and B vaccine between the last LTFU visit and the challenge dose visit.
  • History of hepatitis A or hepatitis B infection between the last LTFU visit and the challenge dose visit.
  • History of anaphylactic reactions following the administration of vaccines.
  • History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
  • Acute disease and/or fever at the time of enrolment.
  • Pregnant or lactating female.
  • Female planning to become pregnant or planning to discontinue contraceptive precautions.
  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: NCT01000324

Locations
Belgium
GSK Investigational Site
Wilrijk, Belgium, 2610
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01000324     History of Changes
Other Study ID Numbers: 112267
Study First Received: October 22, 2009
Results First Received: December 14, 2010
Last Updated: September 4, 2014
Health Authority: Belgium: Federal Agency for Medicines and Health Products, FAMHP

Keywords provided by GlaxoSmithKline:
Hepatitis A
Hepatitis B

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 September 30, 2014