Havrix (HAV): GSK Biologicals hepatitis A vaccine. Engerix -B (HBV): GSK Biologicals hepatitis B vaccine

The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not refl...
Author: Emil Davidson
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The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No.: 112266 (HAB-032 EXT Year 16-20) Title: Antibody persistence and immune memory in healthy adults previously vaccinated with Twinrix™ Adult. Twinrix™ Adult (HAB): GlaxoSmithKline (GSK) Biologicals’ combined hepatitis A and B vaccine. Rationale: This study was a long-term follow-up (LTFU) of the primary study HAB-032 (208127/022). The aim of this LTFU study was to assess the persistence of the immune response and the immune memory to the vaccine antigens, 16-20 years after the primary vaccination of healthy adults with three doses of HAB vaccine. If a subject became seronegative for antibodies against hepatitis A virus (anti-HAV), i.e. anti-HAV antibody concentrations < 15 mIU/mL or had anti-hepatitis B surface antigen (anti-HBs) antibody concentrations < 10 mIU/mL during the LTFU period, the immune memory to the antigens was evaluated by administering a challenge dose of the Havrix™ or Engerix™-B vaccines at the next planned visit. Havrix™ (HAV): GSK Biologicals’ hepatitis A vaccine. Engerix™-B (HBV): GSK Biologicals’ hepatitis B vaccine. For data on the primary study please refer to the CTRS 208127/022. For data on the Year 11 to Year 15 follow-up period please refer to CTRS 100556. Phase: IV Study Period: 27 January 2010 to: − 20 April 2010 (Year 16 LSLV) − 03 March 2011 (Year 17 LSLV) − 16 February 2012 (Year 18 LSLV) − 27 February 2013 (Year 19 LSLV) − 28 February 2014 (Year 20 LSLV) Study Design: Open, single-group LTFU study. Centres: 1 centre in Belgium. Indication: Immunisation of healthy adults against hepatitis A and hepatitis B viruses. Treatment: In the primary study, subjects received 3 doses of HAB vaccine (Lot 1, Lot 2 or Lot 3) according to a 0, 1, 6 month schedule. The 3 groups were pooled into the HAB Group for the data analyses in the LTFU phase. A challenge dose would be administered in this study*, based on serology results at the last available LTFU time point. *At Year 16, 1 subject was administered a challenge dose of HBV vaccine and at Year 18 and 20, 2 subjects were administered a challenge dose of HAV vaccine. It was injected intramuscularly in the deltoid region of the non-dominant arm. None of the subjects received a challenge dose at Year 17 and Year 19. Objectives:  To evaluate anti-HAV and anti-HBs antibody persistence at Years 16, 17, 18, 19 and 20 after a three-dose primary vaccination course with HAB vaccine. Primary Outcome/Efficacy Variable:  Antibody persistence against the study vaccine antigens at each LTFU visit of Years 16, 17, 18, 19 and 20:  Anti-HAV: percentage of seropositive** subjects and geometric mean concentrations (GMCs).  Anti-HBs: percentage of seropositive*** subjects, subjects with anti-HBs concentrations ≥ 10 mIU/mL and GMCs. **Seropositivity for anti-HAV antibodies was defined as antibody concentrations  15 mIU/mL. ***Seropositivity for anti-HBs antibodies was defined as antibody concentrations  6.2 mIU/mL for anti-HBs ChemiLuminescence ImmunoAssay (CLIA). Secondary Outcome/Efficacy Variables: For the challenge dose phase§ Immunogenicity:  Immune response to the study vaccine antigen, before, 14 days and one month after the challenge dose: - Anti-HAV antibody concentrations (for a challenge dose with HAV vaccine). - Anti-HBs antibody concentrations (for a challenge dose with HBV vaccine).  Anamnestic response to the challenge dose.

Anti-HAV anamnestic response to the challenge dose was defined as: - Anti-HAV antibody concentrations ≥ 15 mIU/mL at one month post-challenge dose, in subjects seronegative at the pre-challenge time point. - At least a 2-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in seropositive subjects having anti-HAV antibody concentrations ≥ 100 mIU/mL at the pre-challenge time point. - Or at least a 4-fold increase in anti-HAV antibody concentrations one month after the challenge dose, in seropositive subjects having anti-HAV antibody concentrations < 100 mIU/mL at the pre-challenge time-point. Anti-HBs anamnestic response to the challenge dose was defined as: - Anti-HBs antibody concentrations ≥ 10 mIU/mL, at one month post-challenge dose in subjects seronegative at the pre-challenge time point. - At least a 4-fold increase in anti-HBs antibody concentrations, at one month post-challenge dose in subjects seropositive at the pre-challenge time point. Safety:  Unsolicited adverse events (AEs): - Occurrence, intensity and relationship to vaccination of unsolicited symptoms reported during the 31-day (Days 0 to 30) follow-up period after the challenge dose.  Serious adverse events (SAEs): - Occurrence, intensity and relationship to vaccination of all SAEs following the administration of the challenge dose. §Only

1 HBV vaccine challenge dose and 1 HAV vaccine challenge dose were administered at Year 16 and Year 18 respectively. Statistical Methods: The analyses were performed on the Long-Term (LT) Total cohort and the LT According-to-Protocol (LT ATP) cohort for immunogenicity.  The LT Total cohort included all subjects who returned at each annual time point and who belonged to the Total cohort in the primary study.  The LT-ATP cohort for immunogenicity included all subjects who returned at a particular blood sampling time point and met all eligibility criteria (including respect of specified intervals), who were included in the ATP analysis for the primary study, who did not receive hepatitis A or B vaccination that was not specified in the protocol and were not eliminated for abnormal increase* in antibody concentrations. *Abnormal increase in antibody concentrations as compared to the previous reference time point (i.e. latest time point at which serology data were available) was defined as an increase of two-fold or more in antibody concentrations when the antibody concentration at the reference time point was  100 mIU/mL or a 4-fold or more when the antibody concentration at the reference time point was < 100 mIU/mL. This code was assigned to eliminate from the analysis those subjects who might had been infected with hepatitis A or B, or who might had received an additional unreported vaccine dose not specified by the protocol. Analysis of immunogenicity: The analysis of immunogenicity was performed on the LT Total cohort and the LT-ATP cohort for immunogenicity For the evaluation of antibody persistence, for the pooled group, the percentages of anti-HAV and anti-HBs seropositive subjects and GMCs with their 95% confidence intervals (CIs) were tabulated. The percentage of subjects with anti-HBs concentrations ≥ 10 mIU/mL was also tabulated. Immunogenicity results for the subjects who received a hepatitis A and/or B challenge vaccine dose were tabulated. Anti-HBs and/or anti-HAV antibody concentrations and anamnestic response to the challenge dose were calculated where appropriate. NOTE: A decrease in the specificity of the anti-HB ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following complete retesting and reanalysis for years 16 to 18. Results of year 19 and 20 were only analysed by CLIA. Analysis of safety: The analysis of safety was performed on the LT Total cohort. For the subjects who received a challenge dose of HBV vaccine and HAV vaccine, the occurrence of unsolicited AEs during the 31-day (Day 0 to Day 30) follow-up period after vaccination was tabulated according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred term. The same tabulation was performed for Grade 3 unsolicited AEs and for unsolicited AEs that were assessed by the investigator as possibly related to vaccination. SAEs occurring during the 31-day (Day 0 to Day 30) follow-up period after vaccination were summarized according to MedDRA preferred term. SAEs that were related to study participation (e.g. protocol-mandated procedures, invasive tests) or related to a concurrent

GSK medication were collected and recorded from the time the subject consents to participate in the study until discharge. This period included the long term follow-up visits. Study Population: Male and female subjects who completed the primary vaccination course in the primary study were enrolled into each of the annual LTFU visits. Challenge dose phase: subjects with anti-HAV antibody concentrations

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