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

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatitis A, Hepatitis B

Intervention / Treatment
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* Biological: Twinrix
* Biological: Engerix-B
* Biological: Havrix
* Biological: HBVAXPRO
* 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. 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.

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>Subjects received a single challenge dose of combined hepatitis A/hepatitis B vaccine (Twinrix). | Biological: Twinrix<br>* Intramuscular injection, single dose in left deltoid.<br>|
| Active Comparator: Engerix + Havrix Group<br>Subjects received separate administration of a single challenge dose of hepatitis B vaccine (Engerix) and hepatitis A vaccine (Havrix). | Biological: Engerix-B<br>* Intramuscular injection, single dose in left deltoid.<br>Biological: Havrix<br>* Intramuscular injection, single dose in right deltoid.<br>|
| Active Comparator: HB VAX PRO + Vaqta Group<br>Subjects received separate administration of a single challenge dose of hepatitis B vaccine (HB VAX PRO) and hepatitis A vaccine (Vaqta). | Biological: HBVAXPRO<br>* Intramuscular injection, single dose in the left deltoid.<br>Biological: Vaqta<br>* Intramuscular injection, single dose in right deltoid.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune memory, Combined hepatitis A and B vaccine, > 41 years old