Long-Term Immune Persistence of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Injected According to a 0, 12-month Schedule

Double-blind Randomized Study to Evaluate the Immunogenicity and Reactogenicity of Two Different Lots of GlaxoSmithKline Biologicals' Inactivated Hepatitis A Vaccine Containing 1440 EL.U of Antigen Per mL and Injected According to a 0, 12 Month Schedule in Healthy Adult Volunteers

The aim of this study is to evaluate the persistence of hepatitis A antibodies at 138, 150, 162, 174,186, 198, 210, 222, 234 and 246 months after subjects received their first dose of a 2 dose vaccination schedule of hepatitis A vaccine.

This protocol posting deals with objectives & outcome measures of the extension phase at year 11 to 20.

No additional subjects will be recruited during this long-term follow-up.

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. Months 138, 150, 162, 174,186, 198, 210, 222, 234 and 246), 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 extend the follow up until Year 20.

The study has 10 phases: 100571, 100572, 100573, 100574, 100575, 110677, 110678, 110679, 110680, 110681.

• Study Type: Interventional
• Enrollment (Actual): 135
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Havrix Group; Subjects who received during the primary study 2 doses of Havrix™ at Day 0 and at Month 12.	Biological: Havrix™; 2 doses at 12 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). ** = Regarding Month 234 data, please note that there were 5 subjects for whom serum sample tube was broken and thus due to risk of contamination the test were not performed. Hence these subjects were not included in the LT-ATP cohort for immunogenicity analysis at Month 234. $ = Regarding Month 246 data, please note there was 1 subject for whom serum sample tube was broken and hence scrapped by laboratory. Hence this subject was not included in the LT-ATP cohort for immunogenicity analysis at Month 246.	At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246
Number of Seropositive Subjects Against Hepatitis A Virus	A seropositive subject was a vaccinated subject whose concentrations for antibodies against hepatitis A virus (anti-HAV) were equal or above (>=) the assay cut-off for seropositivity of 15 milli-international units per milliliter (mIU/mL). ** = Regarding Month 234 data, please note that there were 5 subjects for whom serum sample tube was broken and thus due to risk of contamination the test were not performed. Hence these subjects were not included in the LT-ATP cohort for immunogenicity analysis at Month 234. $ = Regarding Month 246 data, please note there was 1 subject for whom serum sample tube was broken and hence scrapped by laboratory. Hence this subject was not included in the LT-ATP cohort for immunogenicity analysis at Month 246.	At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-hepatitis A Virus (Anti-HAV) Antibody Concentration	Concentrations given as GMC expressed as mIU/mL. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198. Please note that value 14.9 means <15.	Before additional vaccination, 14 days after additional vaccination and 30 days after additional vaccination
Number of Subjects Reporting Solicited Local Symptoms	Solicited local symptoms assessed include pain, redness and swelling. Additional vaccination was given to 4 subjects at the Month 186 timepoint and to 1 subject at the Month 198 timepoint.	During the 4-day (Days 0-3) follow-up period after additional vaccination
Number of Subjects Reporting Solicited General Symptoms	Solicited general symptoms assessed include fatigue, fever, gastrointestinal symptoms and headache. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198.	During the 4-day (Days 0-3) follow-up period after additional vaccination
Number of Subjects Reporting 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. 4 subjects received additional vaccination at Month 186 and 1 at Month 198.	During the 30-day follow-up period after additional vaccination
Number of Subjects Reporting Serious Adverse Events (SAE) Assessed by the Investigator as Related to Primary Study Vaccination, Procedures or Lack of Vaccine 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	At Months 138, 150, 162, 174, 186, 198, 210, 222, 234 and 246
Number of Subjects Reporting Serious Adverse Events (SAE) After Additional Vaccination	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. 4 subjects received additional vaccination at Month 186 and 1 at Month 198.	During the 30-day follow-up period after additional vaccination
Number of Subjects Reporting Pregnancies After Additional Vaccination	The number of subjects with outcome of pregnancies reported among subjects who had received the additional vaccination was tabulated. 4 subjects received additional vaccination at Month 186 and 1 subject at Month 198.	At Months 186 and 198

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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 14, 2006
• First Submitted That Met QC Criteria: February 14, 2006
• First Posted (Estimate): February 15, 2006

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: October 23, 2017
• Last Verified: January 1, 2017

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: 100571 (M138); 100572 (M150) (Other Identifier: GSK); 100573 (M162) (Other Identifier: GSK); 100574 (M174) (Other Identifier: GSK); 100575 (M186) (Other Identifier: GSK); 110677 (M198) (Other Identifier: GSK); 110678 (M210) (Other Identifier: GSK); 110679 (Other Identifier: GSK); 110680 (Other Identifier: GSK); 110681 (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. Individual Participant Data Set
   Information identifier: 100571 (M138)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 100571 are summarised with studies 100572, 100573, 100574, 100575, 110677, 110678, 110679, 110680, and 110681 on the GSK Clinical Study
2. Informed Consent Form
   Information identifier: 100571 (M138)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 100571 (M138)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 100571 (M138)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 100571 (M138)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: 100571 (M138)
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register