Long-term Persistence Study in Healthy Adults Previously Vaccinated With Twinrix Adult

An Open Single Centre Study to Evaluate the Long-term Antibody Persistence and Immune Memory Between 16 and 20 Years After the Primary Study HAB-032 (208127/022) in Which Healthy Adults Were Vaccinated With Twinrix Adult Following a Three-dose Schedule.

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 Twinrix Adult in the primary study, HAB-032 (208127/022). The subjects will be invited for blood sampling 16, 17, 18, 19 and 20 years after the primary 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 (Havrix and/or Engerix-B) at the next planned visit.

No new subjects will be recruited during this study.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Hepatitis A
• Intervention / Treatment: Procedure: Blood sampling; Biological: Engerix-B; Biological: Havrix

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 208127/022.
• 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 208127/022.
• Written informed consent obtained from the subject.
• Subjects who participated in the LTFU phase of the 208127/022 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 208127/022.
• History of hepatitis A or hepatitis B infection since the primary study 208127/022.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Twinrix Group; Subjects who received 2 doses of Twinrix (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 Twinrix Group for data analyses during the first long-term follow-up NCT00289718 and this long-term follow-up. A challenge dose of the Havrix or Engerix-B vaccines can be administered in this study based on serology results at each time point.

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: Engerix-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Seropositive for Anti-hepatitis A Virus Antibodies (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies and With Anti-HBs Antibody Concentrations >= 10 Milliinternational Units Per Milliliter (mIU/mL)	Seropositivity for anti-HAV antibodies is defined as antibody concentrations >= 15 milliinternational units per milliliter (mIU/mL). Seropositivity for anti-HBs antibodies is defined as antibody concentrations >= 6.2 mIU/mL.	At Years 16, 17, 18, 19 and 20.
Anti-HAV and Anti-HBs Geometric Mean Concentrations (GMCs)	Concentrations were expressed as GMCs in mIU/mL.	At Years 16, 17, 18, 19 and 20.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-HBs Concentrations After the Challenge Dose of Engerix-B	Concentration was given in mIU/mL. Only 1 subject was eligible for the challenge dose of Engerix-B at the Year 16 time point. Therefore the values for this subject are given without a measure of dispersion.	Before, 14 days and one month (30 days) after the challenge dose of Engerix-B.
Anti-HAV Concentrations After the Challenge Dose of Havrix	Concentration was given in mIU/mL. Only 2 subjects were eligible for the challenge dose of Havrix, one at Year 18 and another at Year 20 time point. Therefore the values for these subject are given without a measure of dispersion.	Before, 14 days and one month (30 days) after the challenge dose of Havrix.
Number of Subjects With Anamnestic Response to the Challenge Dose of Engerix-B	At Year 16 only 1 subject was eligible for the challenge dose of Engerix-B. Anti-HBs anamnestic response to the challenge dose was defined as: Anti-HBs antibody concentrations >= 10 mIU/mL at one month post-challenge dose in subjects seronegative at the pre-challenge time point.; At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time point.	30 days after the challenge dose of Engerix-B.
Number of Subjects With Anamnestic Response to the Challenge Dose of Havrix	Anti-HAV anamnestic response to the challenge dose was defined as: Anti-HAV antibody concentrations ≥ 15 mIU/mL at one month post-challenge dose, in subjects seronegative at the pre-challenge time point.; At least a 2-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in subjects having anti-HAV antibody concentrations ≥ 100 mIU/mL at the pre-challenge time point.; Or at least a 4-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in seropositive subjects having anti-HAV antibody concentrations < 100 mIU/mL at the pre-challenge time-point.	30 days after the challenge dose of Havrix.
Number of Subjects Reporting Unsolicited Adverse Events (AEs)	At Year 16, 1 subject was administered a challenge dose of Engerix-B and at Y18 and Y20, 2 subjects were administered a challenge dose of Havrix. 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.	31 days (Days 0-30) after the challenge dose of Engerix-B and Havrix.
Number of Subjects With Serious Adverse Events (SAEs)	Only 1 subject received a challenge dose at Year 16 of Engerix-B. 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 31-day (Days 0-30) follow-up period after the Engerix-B challenge dose.
Number of Subjects With Serious Adverse Events (SAEs)	One subject received a challenge dose of Havrix at Year 18 and another at Year 20. Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.	During the 31-day (Days 0-30) follow-up period after the Havrix challenge dose.
Number of Subjects Reporting SAEs Related to Study Participation or a Concurrent GSK Medication	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.	Up to Year 20.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• 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.

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 (ACTUAL): January 27, 2010
• Primary Completion (ACTUAL): February 28, 2014
• Study Completion (ACTUAL): February 28, 2014

Study Registration Dates

• First Submitted: December 17, 2009
• First Submitted That Met QC Criteria: December 18, 2009
• First Posted (ESTIMATE): December 21, 2009

Study Record Updates

• Last Update Posted (ACTUAL): February 1, 2019
• Last Update Submitted That Met QC Criteria: August 31, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Hepatitis A and hepatitis B
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A
• Other Study ID Numbers: 112266

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: 112266
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112266
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 112266
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 112266
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 112266
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 112266
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 112266
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No