Evaluation of Immune Memory to Twinrix or Comparator by Challenge Dose Administration 4 Years After Primary Vaccination

Challenge Dose Administration of Twinrix™ or Comparator 4 Years After Primary Vaccination.

Only subjects who participated in the primary study will be invited to participate in the extension phase and the challenge dose phase of this study.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Hepatitis A
• Intervention / Treatment: Biological: Twinrix; Biological: Engerix-B; Biological: Havrix; Biological: HBVAXPRO; Biological: Vaqta

• Study Type: Interventional
• Enrollment (Actual): 506
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site
• Czechia
  • Hradec Kralove, Czechia, 500 01
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
• A male or female who completed the primary vaccination phase of the HAB-160 study (NCT 00603252).
• Written informed consent obtained from the subject.
• If the subject is female, she must be of non-childbearing potential; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions for 30 days prior to vaccination, have a negative pregnancy test and must agree to continue such precautions for two months after the vaccination.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the challenge dose, or planned use during the study period.
• History of any hepatitis A or hepatitis B vaccination or infection since the primary vaccination study.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Acute disease at the time of enrolment.
• Pregnant or lactating female.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Twinrix Group; Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix).	Biological: Twinrix; Intramuscular injection, single dose in left deltoid.
Active Comparator: Engerix + Havrix Group; Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix).	Biological: Engerix-B; Intramuscular injection, single dose in left deltoid.; Biological: Havrix; Intramuscular injection, single dose in right deltoid.
Active Comparator: HB VAX PRO + Vaqta Group; Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta).	Biological: HBVAXPRO; Intramuscular injection, single dose in the left deltoid.; Biological: Vaqta; Intramuscular injection, single dose in right deltoid.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis A (Anti-HAV) Antibodies	Anamnestic response was defined as: for initially seronegative subjects, antibody concentration greater than or equal the cut-off [≥ 15 Milli-International Units per Milliliter (mIU/mL)],; for initially seropositive subjects with pre-vaccination antibody, concentration < 100 mIU/mL: antibody concentration at least four times the pre-vaccination antibody concentration,; for initially seropositive subjects with pre-vaccination antibody concentration ≥ 100 mIU/mL: antibody concentration at least two times the pre-vaccination antibody concentration.	One month after the challenge dose.
Number of Subjects With Anamnestic Response to the Challenge Dose for Anti-hepatitis B Surface Antigen (Anti-HBs) Antibodies	Anamnestic response was defined as : for initially seronegative subjects, antibody concentration ≥ 10 Milli-International Units per Milliliter (mIU/mL),; for initially seropositive subjects: antibody concentration at ≥ 4 fold the pre-vaccination antibody concentration.	One month after the challenge dose.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations	Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.	Prior to administration of challenge dose
Anti-hepatitis A (Anti-HAV) and Anti-hepatitis B Surface Antigen (Anti-HBs) Antibody Concentrations	Concentrations are given as geometric mean concentration (GMCs) expressed as mIU/mL.	Two weeks and one month after the challenge dose
Number of Subjects Reporting Solicited Symptoms	Solicited local symptoms assessed include pain, redness and swelling. Solicited general symptoms assessed include fatigue, gastrointestinal symptoms, headache and temperature (above 37 degree Celsius).	During the 4-day follow-up period after the challenge dose.
Number of Subjects Reporting Unsolicited Symptoms	Unsolicited symptoms = any adverse event (AE) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms was reported as an unsolicited adverse event.	During the 31-day follow-up period after the challenge dose.
Number of Subjects With Serious Adverse Events (SAEs) Since the Last Study Visit of the HAB-160 (NCT00603252) Long-term Follow-up Study Considered by the Investigator to Have a Causal Relationship to Primary Vaccination	A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.	Since the last study visit of the primary study long-term follow-up study up to challenge dose administration (1 year)
Number of Subjects Reporting Serious Adverse Events (SAEs)	A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or is a sign of suspected or confirmed hepatitis A or hepatitis B.	During one month following the administration of the challenge dose

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Chlibek R, von Sonnenburg F, Van Damme P, Smetana J, Tichy P, Gunapalaiah B, Leyssen M, Jacquet JM. Antibody persistence and immune memory 4 years post-vaccination with combined hepatitis A and B vaccine in adults aged over 40 years. J Travel Med. 2011 Mar-Apr;18(2):145-8. doi: 10.1111/j.1708-8305.2010.00499.x. Epub 2011 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: May 26, 2008
• Primary Completion (Actual): November 3, 2008
• Study Completion (Actual): November 3, 2008

Study Registration Dates

• First Submitted: May 23, 2008
• First Submitted That Met QC Criteria: May 27, 2008
• First Posted (Estimate): May 28, 2008

Study Record Updates

• Last Update Posted (Actual): August 17, 2018
• Last Update Submitted That Met QC Criteria: July 2, 2018
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Immune memory; Combined hepatitis A and B vaccine; > 41 years old
• 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: 111572

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. Dataset Specification
   Information identifier: 111572
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 111572
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 111572
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 111572
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 111572
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 111572
   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
• product manufactured in and exported from the U.S.: No