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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis A
• Intervention / Treatment: Biological: Havrix™

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).

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 29 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration	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.	At Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration	Concentrations given as GMC expressed as mIU/mL.	Before the additional dose, 14 days and 30 days after the additional dose
Number of Seropositive Subjects for Anti-HAV Antibodies.	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.	From Year 11 to Year 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigators as Related to Vaccination or to Study Procedures or Lack of Efficacy	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	Years 11, 12, 13, 14, 15, 16, 17, 18, 19 and 20 after the first vaccine dose of the 2-dose primary vaccination
Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms	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.	During the 4-day (Day 0-3) follow-up period after additional vaccination
Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms	Solicited general symptoms assessed included fatigue, fever, gastrointestinal symptoms, and headache.	During the 4-day (Day 0-3) follow-up period after additional vaccination
Number of Subjects Reporting Any, Grade 3 and Related Unsolicited Adverse Events (AE)	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.	During the 30-day follow-up period after additional vaccination (for subjects who received the additional vaccine dose between Year 11 and 15)
Number of Subjects Reporting Serious Adverse Events (SAE)	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.	During the follow-up period after additional vaccination up to Year 20

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Desombere I et al. (2000) Long-term persistence of cellular immunity towards hepatitis A vaccine (HAV) following HAV vaccination. J Antiviral Therapy. 5: 7.
• Van Damme P, Mathei C, Thoelen S, Meheus A, Safary A, Andre FE. Single dose inactivated hepatitis A vaccine: rationale and clinical assessment of the safety and immunogenicity. J Med Virol. 1994 Dec;44(4):435-41. doi: 10.1002/jmv.1890440422.
• Van Damme P et al. (1998) Long-term immunogenicity of a high potency inactivated hepatitis A vaccine. J Hepatol. 28 (suppl.1): 113.
• Van Herck K et al. (2000) Model-based estimates of long-term persistence of vaccine-induced hepatitis A antibodies. J Antiviral Therapy. 5:3-4.
• Van Herck K, Van Damme P. Inactivated hepatitis A vaccine-induced antibodies: follow-up and estimates of long-term persistence. J Med Virol. 2001 Jan;63(1):1-7.
• Van Herck K, Jacquet JM, Van Damme P. 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. 2011 Nov;83(11):1885-91. doi: 10.1002/jmv.22200. Epub 2011 Aug 23.
• Van Herck K, Crasta PD, Messier M, Hardt K, Van Damme P. Seventeen-year antibody persistence in adults primed with two doses of an inactivated hepatitis A vaccine. Hum Vaccin Immunother. 2012 Mar;8(3):323-7. doi: 10.4161/hv.18617. Epub 2012 Feb 13.
• 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.
• Theeten H, Van Herck K, Van Der Meeren O, Crasta P, Van Damme P, Hens N. Long-term antibody persistence after vaccination with a 2-dose Havrix (inactivated hepatitis A vaccine): 20 years of observed data, and long-term model-based predictions. Vaccine. 2015 Oct 13;33(42):5723-5727. doi: 10.1016/j.vaccine.2015.07.008. Epub 2015 Jul 16.
• Hens N, Habteab Ghebretinsae A, Hardt K, Van Damme P, Van Herck K. Model based estimates of long-term persistence of inactivated hepatitis A vaccine-induced antibodies in adults. Vaccine. 2014 Mar 14;32(13):1507-13. doi: 10.1016/j.vaccine.2013.10.088. Epub 2014 Feb 7.

Helpful 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: February 9, 2006
• First Submitted That Met QC Criteria: February 9, 2006
• First Posted (Estimate): February 10, 2006

Study Record Updates

• Last Update Posted (Actual): July 23, 2018
• Last Update Submitted That Met QC Criteria: May 25, 2018
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Hepatitis A; Havrix™
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A
• Other Study ID Numbers: 100576 (Y11); 100577 (Y12) (Other Identifier: GSK); 100578 (Y13) (Other Identifier: GSK); 100579 (Y14) (Other Identifier: GSK); 100580 (Y15) (Other Identifier: GSK); 111028 (Y16) (Other Identifier: GSK); 111029 (Y17) (Other Identifier: GSK); 111030 (Y18) (Other Identifier: GSK); 111031 (Y19) (Other Identifier: GSK); 111032 (Y20) (Other Identifier: GSK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 100576 (Y11)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 100576 (Y11)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 100576 (Y11)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 100576 (Y11)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 100576 are summarised with studies 100577, 100578, 100579, 100580, 111028, 111029, 111030, 111031, and 111032 on the GSK Clinical Study
5. Dataset Specification
   Information identifier: 100576 (Y11)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 100576 (Y11)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register