Hepatitis B Virus Antibody Booster Program for the Production of Hepatitis B Immune Globulin (HBIG)

Study Overview
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Brief Summary
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Hepatitis B Virus Antibody Booster Program

Detailed Description
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The purpose of this study is to vaccinate plasmapheresis donors for collection of high titer plasma to be used in the manufacture of Hepatitis B Immune Globulin (HBIG).

Official Title
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Hepatitis B Virus (HBV) Antibody (Anti-HBs) Booster Program for the Production of Hepatitis B Immune Globulin (HBIG)

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: hepatitis B vaccine
* Biological: hepatitis B vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age 20-55 years. Naïve or previously hepatitis B-vaccinated males or females. Normal and healthy as determined by medical history, physical exam, vital signs and clinical laboratory tests Subject must meet all required/recommended subject suitability criteria that pertain to normal source plasma donors with the following exception: Subjects who previously tested positive for HBsAg may be accepted into the anti- HBs program provided they now test negative and meet all other normal donor suitability criteria. Written informed consent. Exclusion Criteria: Subjects who have received a hepatitis B vaccination in the previous six months. History of hypersensitivity to yeast or any components of the Engerix-B® vaccine History of hypersensitivity to any hepatitis B-containing vaccine. Use of any investigational product within the past 30 days or during the course of the study. Use of steroids or immunosuppressives during the study period. Received immunosuppressive therapy (including systemic steroids) within 30 days before study entry Subjects who have received cytotoxic therapy (in the previous 5 years prior to study entry) Received parenteral immune globulin products or blood products within 3 months before study entry with the following exceptions: RhoGAM (or equivalent anti-D immune globulin) within 6 weeks before study entry; Pertussis immune globulin: no exclusion Received parenteral immune globulin products or blood products (within 3 months before study entry) Past, present, or suspected IV drug use Positive HIV, HBV* or HCV test result (*except as described above in Inclusion Criteria) Autoimmune disease (such as, but not limited to demyelinating disease) Subjects with cancer, heart disease (including hospitalization for myocardial infarction, arrhythmia, syncope, congestive heart failure), uncontrolled hypertension, uncontrolled insulin-dependent diabetes mellitus, seizures, kidney disease Severely or morbidly obese, or higher obesity classification, which corresponds to BMI of 35 or higher Pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Schedule 1- Standard dose primary vaccination series<br>Schedule 1 subjects received 20 µg/1.0 mL of Engerix-B® on Day 0, Day 30, Day 180 with booster of 20 µg/1.0 mL of Engerix-B® every 120 days (4 months) (after Day 180 vaccination) | Biological: hepatitis B vaccine<br>* Primary vaccination series 20 µg/1.0 mL at baseline, month 1, month 6; followed by booster vaccinations 20 µg/1.0 mL<br>* Other names: Engerix-B;|
| Experimental: Schedule 2 - High dose primary vaccination series<br>Schedule 1 subjects received 40 µg/1.0 mL of Engerix-B® on Day 0, Day 30, Day 60, Day 180 with booster of 20 µg/1.0 mL of Engerix-B® every 120 days (4 months) (after Day 180 vaccination) | Biological: hepatitis B vaccine<br>* Primary vaccination series 40 µg/2.0 mL at baseline, month 1, month 2, month 6; followed by booster vaccinations 20 µg/1.0 mL<br>* Other names: Engerix-B;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison Between Vaccination Schedules Using Day 210 Anti-HBs Antibody Titers AUC(0-t) | The primary endpoint for study HB-012 is area under the anti-HBs antibody concentration-time curve (AUC0-t) through Day 210. This endpoint was chosen because it allowed for the assessment of changes in anti HBs antibody concentration over time, and addressed one of the study objectives: to determine the effectiveness of Engerix-B booster vaccinations in the production of high anti-HBs titer plasma. By comparing AUC0-t between the two dosing schedules, the primary endpoint of AUC0-t also addressed the study objective to determine the optimal vaccination schedule to obtain high anti-HBs titer plasma for the manufacture of HepaGam B. | Day 0 to Day 210 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison Between Vaccination Schedules Using Anti-HBs Titers on Day 210 | Anti-HBs titers on Day 210 were assessed as a measure of the anti-HBs level attained following completion of the primary vaccination series; the final primary-series vaccination was administered for both Schedules on Day 180. | Day 210 | 
| Comparison Between Vaccination Schedules Using Time to Reach 55 IU/mL Anti-HBs Plasma Titer Level | Time to reach 55 IU/mL was calculated based on the actual time, in days, from the baseline visit (Day 0) to the first time to reach an anti-HBs titer of 55 IU/mL using Kaplan - Meier methods. | up to Day 258 | 
| Time to Reach Anti-HBs Level of 80 IU/mL | Time to reach 80 IU/mL was calculated based on the actual time, in days, from the baseline visit (Day 0) to the first time to reach an anti-HBs titer of 80 IU/mL. | 0-12 months | 
| Comparison Between Vaccination Schedules Using Time to Peak Anti-HBs Titer | Time to reach peak anti-HBs plasma titer was calculated based on the actual times in days, from the baseline visit (Day 0) to the peak titer using Kaplan-Meier methods. | Up to Day 258 |