Effect of Risk Factors Likely to Influence Immuno of Combined Hepatitis A & B Vacc vs Monovalent Hepatitis A & B Vacc

Evaluate the Effect of Several Risk Factors That Are Likely to Influence the Immunogenicity of GSK Biologicals' Combined Hepatitis A & B Vaccine, vs Separately Administered Monovalent Hepatitis A and Hepatitis B Vaccines

The focus of this study is to evaluate how risk factors like age, gender, body mass index, smoking, alcohol consumption, etc. can influence immune response when subjects are vaccinated with GSK Biologicals' combined hepatitis A/hepatitis B vaccine or monovalent hepatitis A and B vaccines (from GSK Biologicals' or different manufacturers). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Study Overview

• Status: Completed
• Conditions: Hepatitis B; Hepatitis A
• Intervention / Treatment: Biological: TWINRIX™; Biological: Engerix™-B; Biological: HAVRIX™; Biological: HB VAX PRO™; Biological: Vaqta™

Detailed Description

The study will also evaluate the persistence of hepatitis A and hepatitis B antibodies at months 12, 24 and 36 after the first dose of primary vaccination course.

• Study Type: Interventional
• Enrollment (Actual): 596
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Wilrijk, Belgium, 2610
    • GSK Investigational Site
• Czechia
  • Hradec Kralove, Czechia, 500 01
    • GSK Investigational Site
• Germany
  • Brandenburg
    • Finsterwalde, Brandenburg, Germany, 03238
      • GSK Investigational Site
  • Sachsen
    • Dresden, Sachsen, Germany, 01129
      • GSK Investigational Site
    • Geringswalde, Sachsen, Germany, 09326
      • GSK Investigational Site
    • Pirna, Sachsen, Germany, 01796
      • GSK Investigational Site
  • Schleswig-Holstein
    • Bad Bramstedt, Schleswig-Holstein, Germany, 24576
      • GSK Investigational Site
    • Bad Segeberg, Schleswig-Holstein, Germany, 23795
      • GSK Investigational Site
    • Elmshorn, Schleswig-Holstein, Germany, 25335
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 41 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• 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 should be enrolled in the study.
• Healthy and non-healthy male or female aged 41 years or older at the time of the first vaccination.
• Written informed consent obtained from the subject.
• No serological signs of hepatitis A or B infection at screening.
• 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 completion of the vaccination series.

Exclusion criteria:

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
• History of any hepatitis A or hepatitis B vaccination or infection, since the primary vaccination study 100382.
• 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.
• Female planning to become pregnant or planning to discontinue contraceptive precautions during the primary vaccination period.

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; Healthy and non-healthy male or female subjects, aged 41 years or older, who received combined Twinrix™ (720/20) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule.	Biological: TWINRIX™; Intramuscular injection, 3 doses
Active Comparator: Engerix-B+Havrix Group; Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of Engerix™-B (20 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Havrix™ (1440 EL.U) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	Biological: Engerix™-B; Intramuscular injection, 3 doses; Biological: HAVRIX™; Intramuscular injection, 2 doses
Active Comparator: HB VAX PRO+Vaqta Group; Healthy and non-healthy male or female subjects, aged 41 years or older, who received separate administrations of HB VAX PRO™ (10 μg) vaccine, administered intramuscularly in the left deltoid region, according to a 0, 1 and 6 month schedule and Vaqta™ (50 IU) vaccine, administered intramuscularly in the right deltoid region, according to a 0 and 6 month schedule.	Biological: HB VAX PRO™; Intramuscular injection, 3 doses; Biological: Vaqta™; Intramuscular injection, 2 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody Concentrations for Anti-hepatitis A Virus (Anti-HAV) and Anti-hepatitis B Surface (Anti-HBs) Antigens	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively.	At Month 7 after Twinrix vaccination
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration ≥ 15mIU/mL; seropositivity for anti-HBs antibodies was defined as anti-HBs antibody concentration ≥ 3.3 mIU/mL.	At Month 7
Number of Seroprotected Subjects Against Hepatitis B Surface (HBs) Antigen	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL.	At Month 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-HAV and Anti-HBs Antibody Concentrations	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively.	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Gender	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by gender (females and males).	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Age	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by age as follows: ≤ 50 years of age (YOA), 51-60 YOA and ≥ 61 YOA.	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Body Mass Index (BMI)	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by BMI as follows: healthy, overweight and obese.	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Smoking Status	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by smoking status (smokers and non-smokers).	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Alcohol Consumption	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by alcohol consumption as follows: None or Mild, Moderate and Heavy.	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Concomitant Medication	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by concomitant medication (concomitant medication and no concomitant medication).	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value, by Medical Condition	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. The seropositivity rates were stratified by medical condition as follows: no medical condition, past medical condition and current medical condition.	At Month 7
Number of Seroprotected Subjects Against HBs Antigen, by Gender	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by gender (females and males).	At Month 7
Number of Seroprotected Subjects Against HBs Antigen, by Age	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by age as follows: ≤ 50 years of age (YOA), 51-60 YOA and ≥ 61 YOA.	At Month 7
Number of Seroprotected Subjects Against HBs Antigen, by BMI	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by BMI as follows: healthy, overweight and obese.	At Month 7
Number of Seroprotected Subjects Against HBs Antigen, by Smoking Status	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by smoking status (smokers and non-smokers).	At Month 7
Number of Seroprotected Subjects Against HBs Antigen, by Alcohol Consumption	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by alcohol consumption as follows: none or mild, moderate and heavy.	At Month 7
Number of Seroprotected Subjects Against HBs Antigen, by Concomitant Medication	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by concomitant medication (concomitant medication and no concomitant medication).	At Month 7
Number of Seroprotected Subjects Against HBs Antigen, by Medical Condition	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. The seroprotection rates were stratified by medical condition as follows: no medical condition, past medical condition and current medical condition.	At Month 7
Anti-HAV and Anti-HBs Antibody Concentrations, by Gender	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by gender (females and males).	At Month 7
Anti-HAV and Anti-HBs Antibody Concentrations, by Age	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by age as follows: ≤ 50 years of age (YOA), 51-60 YOA and ≥ 61 YOA.	At Month 7
Anti-HAV and Anti-HBs Antibody Concentrations, by BMI	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by BMI as follows: healthy, overweight and obese.	At Month 7
Anti-HAV and Anti-HBs Antibody Concentrations, by Smoking Status	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by smoking status (smokers and non-smokers).	At Month 7
Anti-HAV and Anti-HBs Antibody Concentrations, by Alcohol Consumption	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by alcohol consumption as follows: none or mild, moderate and heavy.	At Month 7
Anti-HAV and Anti-HBs Antibody Concentrations, by Concomitant Medication	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by concomitant medication (concomitant medication and no concomitant medication).	At Month 7
Anti-HAV and Anti-HBs Antibody Concentrations, by Medical Condition	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. The antibody concentrations were stratified by medical condition as follows: no medical condition, past medical condition and current medical condition.	At Month 7
Number of Subjects With Anti-HAV and Anti-HBs Antibody Concentrations Above the Cut-off Value	Seropositivity for anti-HAV antibodies was defined as anti-HAV antibody concentration equal to or above (≥) 15 mIU/mL and anti-HBs seropositivity was defined as anti-HBs antibody concentrations ≥ 3.3 mIU/mL. Anti-HBs AUSAB = anti-HBs antibody concentrations were tested with AUSAB EIA /Abbott assay; Anti-HBs in-house = anti-HBs antibody concentrations were tested with in-house assay (bridging).	At Month 12 (M12), Month 24 (M24) and Month 36 (M36)
Number of Seroprotected Subjects Against Hepatitis B Surface (HBs) Antigen	A seroprotected subject was defined as a vaccinated subject with a serum anti-HBs antibody concentration equal to or above (≥) 10 mIU/mL. Anti-HBs AUSAB = anti-HBs antibody concentrations were tested with AUSAB EIA /Abbott assay; Anti-HBs in-house = anti-HBs antibody concentrations were tested with in-house assay (bridging).	At Month 12 (M12), Month 24 (M24) and Month 36 (M36)
Anti-HAV and Anti-HBs Antibody Concentrations	Anti-HAV and anti-HBs antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in milli International Units per milliliter (mIU/mL). The reference seropositivity cut-off values for anti-HAV and anti-HBs antibodies were equal to or above (≥) 15 mIU/mL and ≥ 3.3 mIU/mL, respectively. Anti-HBs AUSAB = anti-HBs antibody concentrations were tested with AUSAB EIA /Abbott assay; Anti-HBs in-house = anti-HBs antibody concentrations were tested with in-house assay (bridging).	At Month 12 (M12), Month 24 (M24) and Month 36 (M36)
Number of Subjects With Serious Adverse Events (SAEs)	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: 3 subjects reported SAEs prior to administration of the first dose of vaccination.	From Day 0 up to Month 7
Number of Subjects With SAEs	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Note: 3 subjects reported SAEs prior to administration of the first dose of vaccination.	At Month 12 (M12), Month 24 (M24) and Month 36 (M36)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Van der Wielen M, Van Damme P, Chlibek R, Smetana J, von Sonnenburg F. Hepatitis A/B vaccination of adults over 40 years old: comparison of three vaccine regimens and effect of influencing factors. Vaccine. 2006 Jun 29;24(26):5509-15. doi: 10.1016/j.vaccine.2006.04.016. Epub 2006 May 4.

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): November 24, 2003
• Primary Completion (Actual): December 21, 2004
• Study Completion (Actual): December 21, 2004

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): November 15, 2019
• Last Update Submitted That Met QC Criteria: October 29, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Hepatitis B; Hepatitis A; Combined hepatitis A and hepatitis B vaccine; Monovalent hepatitis A and hepatitis B vaccines
• 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: 100382; 100383 (Other Identifier: GSK); 100384 (Other Identifier: GSK); 100385 (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.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 100382
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 100382
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 100382
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register. The results of this study 100382 are summarised with studies 100383, 100384, and 100385 on the GSK Clinical Study Register.
4. Clinical Study Report
   Information identifier: 100382
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 100382
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 100382
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register