Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine, Injected According to 0, 6-month Schedule

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00289757
First received: February 9, 2006
Last updated: July 24, 2014
Last verified: May 2014
  Purpose

The aim of this study is to evaluate the long-term persistence of hepatitis A antibodies at 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 years after subjects received their first dose of a 2 dose vaccination schedule of hepatitis A vaccine.


Condition Intervention Phase
Hepatitis A
Biological: Havrix™
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Double-blind, Randomized Study to Evaluate the Immunogenicity and Reactogenicity of Three Different Lots of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Containing 1440 EL.U of Antigen Per mL and Injected According to a 0, 6 Month Schedule in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration [ Time Frame: At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination ] [ Designated as safety issue: No ]

    Concentrations given as geometric mean concentration (GMC) expressed as milli-international unit per millilitre (mIU/mL).

    The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging.


  • Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration [ Time Frame: Before the additional dose, 14 days and 30 days after the additional dose ] [ Designated as safety issue: No ]
    Concentrations given as GMC expressed as mIU/mL.

  • Number of Seropositive Subjects for Anti-HAV Antibodies. [ Time Frame: From Year 11 to Year 20 ] [ Designated as safety issue: No ]

    Seropositivity for anti-HAV antibodies defined as antibody concentrations ≥ 15 mIU/mL for Year 11 to Year 20 time points.

    The laboratory assay was changed at Year 11, thus the blood samples were with both the old and the new assay for the sake of bridging.



Secondary Outcome Measures:
  • Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy [ Time Frame: Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination ] [ Designated as safety issue: No ]
    An 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 Any and Grade 3 Solicited Local Symptoms [ Time Frame: During the 4-day (Day 0-3) follow-up period after additional vaccination ] [ Designated as safety issue: No ]

    Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain = symptom that prevented normal activities. Grade 3 redness and swelling = redness or swelling above 30 mm and persisting more than 24 hours.

    Any = incidence of a particular symptom regardless of intensity.


  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms [ Time Frame: During the 4-day (Day 0-3) follow-up period after additional vaccination ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed included fatigue, fever, gastrointestinal symptoms, and headache.

  • Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE) [ Time Frame: During the 30-day follow-up period after additional vaccination (for subjects who received the additional vaccine dose between Year 11 and 15) ] [ Designated as safety issue: No ]

    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Grade AE = produced significant impairment of functioning or incapacitation and was a definite hazard to the subject's health.

    Related AE = assessed by the investigator as related to the study vaccination.


  • Number of Subjects Reporting Serious Adverse Events (SAE) [ Time Frame: During the follow-up period after additional vaccination up to Year 20 ] [ Designated as safety issue: No ]
    An 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.


Enrollment: 78
Study Start Date: January 2004
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Havrix Group

Subjects who received 2 doses of Havrix™ (lot A, B or C) in the primary study.

As lot to lot consistency was assessed during the primary study, the 3 groups (lot A, B or C) were pooled into the Havrix Group for data analyses during the long term follow-up.

Biological: Havrix™
2 doses at 6 months interval

Detailed Description:

This is a long-term follow-up study at Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after primary vaccination with GSK Biologicals' hepatitis A vaccine (two-dose schedule). To evaluate the long-term antibody persistence, volunteers will donate a blood sample at Years 11, 12, 13, 14,15, 16, 17, 18, 19 and 20 after the first vaccine dose of the primary vaccination course to determine their anti-hepatitis A (anti-HAV) antibody concentrations If a subject has become seronegative for anti-HAV antibodies during any of the long-term blood sampling time point (i.e. Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 years), he/ she will be offered an additional vaccine dose. A blood sample will be taken on the day of the additional vaccination, 14 days and one month after additional vaccination to evaluate the immune response following this vaccination.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007 and to include an extended follow up period up to Year 20 after primary vaccination.

The study has 10 phases (100576, 100577, 100578, 100579, 100580, 111028, 111029, 111030, 111031, 111032).

  Eligibility

Ages Eligible for Study:   29 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Subjects who had received at least one dose of the study vaccine in the primary study
  • Written informed consent will have been obtained from the subjects before the blood sampling visit of each year.
  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: NCT00289757

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

Publications:
Van Herck K et al. (2011) Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years. J Med Virol. 83(11):1885-1891.
Van Damme P et al. (1998) Long-term immunogenicity of a high potency inactivated hepatitis A vaccine. J Hepatol. 28 (suppl.1): 113.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00289757     History of Changes
Other Study ID Numbers: 100576 (Y11), 100577 (Y12), 100578 (Y13), 100579 (Y14), 100580 (Y15), 111028 (Y16), 111029 (Y17), 111030 (Y18), 111031 (Y19), 111032 (Y20)
Study First Received: February 9, 2006
Results First Received: December 10, 2009
Last Updated: July 24, 2014
Health Authority: Belgium: Institutional Review Board

Keywords provided by GlaxoSmithKline:
Havrix™
Hepatitis A

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections

ClinicalTrials.gov processed this record on October 19, 2014