Evaluation of Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in Previously Vaccinated Children

Study Overview
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Brief Summary
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This study will evaluate the persistence of immunity to hepatitis B 10 to 11 years after vaccination with Infanrix hexa™ or Engerix™-B and also the ability to mount an immune response to the challenge dose of Engerix™-B.

Detailed Description
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Subjects who participated in the primary study 217744/031 (NCT01457495) will be invited at the age of 11-12 years to participate in this follow-up study.

Official Title
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Antibody Persistence and Immune Memory Against the Hepatitis B Antigen in 11-12 Year Old Children, Previously Vaccinated With DTPa-HBV-IPV/Hib Vaccine in Study 217744/031

Conditions
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Hepatitis B

Intervention / Treatment
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* Biological: Engerix™-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/Legally acceptable representative) can and will comply with the requirements of the protocol should be enrolled in the study. A male or female aged 11-12 years at the time of study entry (from and including the 11th birthday until and excluding the 13th birthday). Written informed consent obtained from the parent or Legally Acceptable Representative of the subject. Study procedures will be explained to subjects and depending on their understanding, optional informed assent will be sought at the discretion of the investigator. Written informed assent obtained from the subject in addition to the informed consent signed by the parent(s)/ Legally Acceptable Representative (s). Healthy subjects as established by medical history and clinical examination before entering into the study. Subjects who have received all three doses of Infanrix hexa or Engerix-B in the primary study 217744/031 (NCT01457495). 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 during the entire treatment period and for 2 months after completion of the vaccination series. Exclusion Criteria: Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product. Child in care. Use of any investigational or non-registered product drug or vaccine) other than the study vaccine within 30 days preceding the challenge dose of HBV vaccine, or planned use during the study period. Receipt of hepatitis B (containing) vaccine after vaccination in the primary study 217744/031 (NCT01457495). History of hepatitis B disease. Planned administration/administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before and ending 30 days after the HBV vaccine challenge dose. Administration of immunoglobulins and/or any blood products within the three months preceding the challenge dose of HBV vaccine or planned administration during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the challenge dose of HBV vaccine. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions. Known hypersensitivity to any component of the HBV vaccine or evidence of hypersensitivity after previous immunisation with a vaccine containing the hepatitis B component. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic setting Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 12 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infanrix-hexa/Engerix-B Group<br>Subjects aged 11-12 year old received 3 doses of Infanrix-hexa vaccine in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. | Biological: Engerix™-B<br>* Intramuscular, single dose<br>|
| Active Comparator: Infanrix-IPV+Hib/Engerix-B Group<br>Subjects aged 11-12 year old received 3 doses of Infanrix-IPV+Hib and Engerix-B vaccines in the primary study (217744/031 (NCT01457495)) and a challenge dose of Engerix-B vaccine in this study. Engerix-B was administered as a single dose intramuscularly into the deltoid region of the non-dominant arm. | Biological: Engerix™-B<br>* Intramuscular, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-hepatitis B (Anti-HBs) Antibody Concentration Equal to or Above (≥) 100 Milli-International Units Per Milliliter (mIU/mL) | A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. | One month after a challenge dose of Engerix-B vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With an Anamnestic Response to a Challenge Dose | The anamnestic response was defined as: at least (≥) a 4-fold rise in post-challenge dose anti-HBs antibody concentrations in subjects seropositive at the pre-challenge dose time point. - Post-challenge dose anti-HBs antibody concentrations ≥ 10 mIU/mL in seronegative subjects at the pre-challenge dose time point. A seropositive/seronegative subject is a subject with anti-HBs antibody concentration ≥/lower than (<) 6.2 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off. | Before and one month after a challenge dose of Engerix-B vaccine | 
| Number of Subjects With Anti-HBs Antibody Concentration ≥ 6.2 mIU/mL | A seropositive subject was defined as a subject with anti-HBs antibody concentration ≥ the 6.2 mIU/mLcut-off. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis and the initial 3.3 mIU/mL seropositivity cut-off was revised into the new 6.2 mIU/mL cut-off. | Before and one month after a challenge dose of Engerix-B vaccine | 
| Number of Subjects With Anti-HBs Antibody Concentration ≥ 10 mIU/mL | A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB enzyme-linked immunosorbent assay (ELISA) had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. | Before and one month after a challenge dose of Engerix-B vaccine | 
| Number of Subjects With Anti-HBs Antibody Concentration ≥ 100 mIU/mL | A seroprotected subject was defined as a subject with anti-HBs antibody concentration ≥ 10 mIU/mL. A decrease in the specificity of the anti-HB ELISA had been observed in some studies for low levels of antibody (10-100 mIU/mL). All the available blood samples initially tested with ELISA were re-tested using the Chemi Luminescence Immuno Assay (CLIA) approved by the US Food and Drug Administration (FDA). The table shows updated results following partial or complete retesting/reanalysis. | Before the challenge dose of Engerix-B vaccine | 
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed were pain, redness and swelling. | During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed were fatigue, gastrointestinal, headache and temperature (Temperature is defined as axillary temparature equal to or above 37.5 degrees Celsius (°C)). | During the 4-day (Days 0-3) follow-up period after a challenge dose of Engerix-B vaccine | 
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. | During the 31-day (Days 0-30) follow-up period after a challenge dose of Engerix-B vaccine | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that results in death, are life threatening, require hospitalization or prolongation of hospitalization, results in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subjects. | After the challenge dose of Engerix-B vaccine up to the study end | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistence, challenge dose, Engerix-B, immune response