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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Hepatitis B, Hepatitis A

Intervention / Treatment
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* Biological: TWINRIX™
* Biological: Engerix™-B
* Biological: HAVRIX™
* Biological: HB VAX PRO™
* Biological: Vaqta™


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 41 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Twinrix Group<br>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™<br>* Intramuscular injection, 3 doses<br>|
| Active Comparator: Engerix-B+Havrix Group<br>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<br>* Intramuscular injection, 3 doses<br>Biological: HAVRIX™<br>* Intramuscular injection, 2 doses<br>|
| Active Comparator: HB VAX PRO+Vaqta Group<br>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™<br>* Intramuscular injection, 3 doses<br>Biological: Vaqta™<br>* Intramuscular injection, 2 doses<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Combined hepatitis A and hepatitis B vaccine, Hepatitis B, Hepatitis A, Monovalent hepatitis A and hepatitis B vaccines