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

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.

Time frame: Day 0 to Day 210

Population: The efficacy analysis population was used to assess the primary endpoint and to generate study conclusions. The efficacy analysis population included all subjects who were vaccinated prior to the interim analysis cut-off date of 1 September 2010 and assessed on visit 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.

Time frame: Day 210

Population: The population used for this analysis, efficacy population responders, includes any subject who reached Day 210 (with the exception of subjects with all anti-HBs titer results \< 2 IU/mL who were considered non-responders), 14 in Schedule 1 and 21 in Schedule 2. However, four subjects (1 in schedule 1 and 3 in schedule 2) were excluded due to missing day 210 titers.

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.

Time frame: Up to Day 258

Population: The efficacy population responder subset was used. The interim analysis cut-off date was used as the censoring date, except in the case where the subject was lost to follow-up or withdrawn prior to the interim analysis cut off date.

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.

Time frame: up to Day 258

Population: The efficacy population responder subset was used. If a subject's anti-HBs titer levels did not reach 55 IU/mL on or before the cut-off date September 1, 2010, the subject was included as a censored observation. The last anti-HBs assessment date or interim analysis cut-off date, whichever was later, was used as the censoring date. In schedule 1, 3 subjects reached anti-HBs titer level of 55 IU/mL. In schedule 2, 4 subjects reached a titer of 55 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.

Time frame: 0-12 months

Population: The efficacy population responder subset was used. If a subject's anti-HBs titer levels did not reach 80 IU/mL on or before the cut-off date September 1, 2010, the subject was included as a censored observation. The last anti-HBs assessment date or interim analysis cut-off date, whichever was later, was used as the censoring date. In schedule 1, no subjects reached anti-HBs titer level of 80 IU/mL. In schedule 2, 2 subjects reached a titer of 80 IU/mL.