Study to Compare the Efficacy of GSK Biologicals' Adjuvants in Combination With the Antigen of the Hepatitis B Vaccine

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00805389
First received: December 5, 2008
Last updated: February 12, 2015
Last verified: June 2014
  Purpose

The aim of this Observer-blind study is to compare different Adjuvant Systems with the same, well-known antigen (HBsAg) already used in the GSK marketed vaccines against Hepatitis B (Engerix-BTM and FendrixTM), in order to better understand the immune response induced by each of the Adjuvant System.

This Protocol Posting has been updated following Protocol amendment 6, October 2009. The section impacted is Eligibility Criteria


Condition Intervention Phase
Hepatitis B
Biological: Engerix-B™
Biological: Fendrix™
Biological: GSK Biologicals' Hepatitis B vaccines (GSK223192A)
Biological: HBsAg (Booster injection)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Comparison of the Immunogenicity and Safety of Various Investigational and Licensed Formulations of Hepatitis B Surface Antigen (HBsAg) Vaccines.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells . [ Time Frame: At Days 0, 14, 30, 44 and 60 ] [ Designated as safety issue: No ]
    The number of HB-CD4+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD40L), Interleukin (IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs). Results for the Day 44 time point are the primary results among the outcome measure results presented.


Secondary Outcome Measures:
  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 8 (CD8+) T Cells. [ Time Frame: At Days 0, 14, 30, 44, and 60 ] [ Designated as safety issue: No ]
    The number of HB-CD8+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD40L), Interleukin (IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs).

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells . [ Time Frame: At Days 0, 180 and 360 ] [ Designated as safety issue: No ]
    The number of HB-CD4+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD-40L), Interleukin(IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs).

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 8 (CD8+) T Cells. [ Time Frame: At Days 0, 180 and 360 ] [ Designated as safety issue: No ]
    The number of HB-CD8+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD-40L), Interleukin(IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs).

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells. [ Time Frame: At Days 0, 360 and 374 ] [ Designated as safety issue: No ]
    The number of HB-CD4+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD-40L), Interleukin(IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs).

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 8 (CD8+) T Cells [ Time Frame: At Days 0, 360 and 374 ] [ Designated as safety issue: No ]
    The number of HB-CD8+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD-40L), Interleukin(IL)-2, Interferon-gamma (IFN-g), Tumor Necrosis Factor-alpha (TNF-a), IL-13 and IL-17 was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs).

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells [ Time Frame: At Days 0, 14, 30, 33, 37, 44 and 60 ] [ Designated as safety issue: No ]
    The number of HB-CD4+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD-40L), Interleukin(IL)-2, Interferon-gamma (IFN-g), and Tumor Necrosis Factor-alpha (TNF-a) was measured by Intracellular Cytokine Staining (ICS), using whole blood. This analysis was performed solely on eligible subjects enrolled at the Centre for Vaccinology (CEVAC) in Ghent, Belgium.

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 8 (CD8+) T Cells [ Time Frame: At Days 0, 14, 30, 44, 60 and 180 ] [ Designated as safety issue: No ]
    The number of HB-CD8+ T cells (per million cells) producing 2 or more markers amongst Cluster Differentiation 40 Ligand (CD-40L), Interleukin(IL)-2, Interferon-gamma (IFN-g), and Tumor Necrosis Factor-alpha (TNF-a) was measured by Intracellular Cytokine Staining (ICS), using whole blood. This analysis was performed solely on eligible subjects enrolled at the Centre for Vaccinology (CEVAC) in Ghent, Belgium.

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells Expressing T Helper Cell Type 1 Response/T Helper Cell Type 2 Response (Th1/Th2) Cytokine Profile [ Time Frame: At Days 0, 14, 30, 44 and 60 ] [ Designated as safety issue: No ]
    The number of HB-specific CD4+ T cells (per million cells) expressing Th1 and/or Th2 cytokine profile was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs).

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 4 (CD4+) T Cells Expressing T Helper Cell Type 1 Response/T Helper Cell Type 2 Response (Th1/Th2) Cytokine Profile [ Time Frame: At Days 0 and 180 ] [ Designated as safety issue: No ]
    The number of HB-specific CD4+ T cells (per million cells) expressing Th1 and/or Th2 cytokine profile was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs).

  • Number of Hepatitis B (HB)-Specific Cluster of Differentiation 8 (CD8+) T Cells Expressing T Helper Cell Type 1 Response/T Helper Cell Type 2 Response (Th1/Th2) Cytokine Profile [ Time Frame: At Days 0, 14, 30, 44, 60, 180 ] [ Designated as safety issue: No ]
    The number of HB-specific CD8+ T cells (per million cells) expressing Th1 and/or Th2 cytokine profile was measured by Intracellular Cytokine Staining (ICS), using frozen Peripheral Blood Mononuclear Cells (PBMCs). Since T helper cells are all CD4 T cell, no Th1/ Th2 cytokine profile was performed for CD8 T cells.

  • Anti-Hepatitis B (Anti-HB) Antibody Concentrations in Serum, as Measured by Chemi Luminescence Immuno Assay (CLIA) [ Time Frame: At Days 0, 30, 44, and 60 ] [ Designated as safety issue: No ]
    Anti-HBs antibody concentrations in serum were measured by CLIA Assay. Concentrations were presented as geometric mean concentrations, in milli-International Units per milliliter (mIU/mL). Analysis was initially planned to be performed by Enzyme-Linked Immunosorbent Assay (ELISA). 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). Following these laboratory quality issues, GSB Biologicals decided to stop testing with the HBs in-house ELISA and to have the anti-HB analysis performed using the new validated CLIA assay. This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Anti-Hepatitis B (Anti-HB) Antibody Concentrations in Serum, as Measured by Chemi Luminescence Immuno Assay (CLIA) [ Time Frame: At Days 0, 180 and 360 ] [ Designated as safety issue: No ]
    Anti-HBs antibody concentrations in serum were measured by CLIA Assay. Concentrations were presented as geometric mean concentrations, in milli-International Units per milliliter (mIU/mL). Analysis was initially planned to be performed by Enzyme-Linked Immunosorbent Assay (ELISA). 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). Following these laboratory quality issues, GSB Biologicals decided to stop testing with the HBs in-house ELISA and to have the anti-HB analysis performed using the new validated CLIA assay. This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Anti-Hepatitis B (Anti-HB) Antibody Concentrations in Serum, as Measured by Chemi Luminescence Immuno Assay (CLIA) [ Time Frame: At Days 0, 374 and 390 ] [ Designated as safety issue: No ]
    Anti-HBs antibody concentrations in serum were measured by CLIA Assay. Concentrations were presented as geometric mean concentrations, in milli-International Units per milliliter (mIU/mL). Analysis was initially planned to be performed by Enzyme-Linked Immunosorbent Assay (ELISA). 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). Following these laboratory quality issues, GSB Biologicals decided to stop testing with the HBs in-house ELISA and to have the anti-HB analysis performed using the new validated CLIA assay. This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Hepatitis B (HB)-Specific Memory B Cells [ Time Frame: At Days 0, 30, 37, 44 and 60. ] [ Designated as safety issue: No ]
    The number of HB-specific memory B-cells (HB mem-B cells), per million cells - expressed through tabulation of interquartile range data - was measured by B-cell Enzyme-Linked Immunosorbent Spot (ELISPOT) using Peripheral Blood Mononuclear Cells (PBMCs). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Hepatitis B (HB)-Specific Memory B Cells [ Time Frame: At Days 180 and 360 ] [ Designated as safety issue: No ]
    The number of HB-specific memory B-cells (HB mem-B cells), per million cells - expressed through tabulation of interquartile range data - was measured by B-cell Enzyme-Linked Immunosorbent Spot (ELISPOT) using Peripheral Blood Mononuclear Cells (PBMCs). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Concentrations of the Interferon-gamma (IFN-g), Interleukin (IL)-1beta, IL-5, IL-6, IL-10, Tumor Necrosis Factor-alpha, IFN-g-inducible Protein-10 and Monocyte Chemotactic Protein-1 Cytokines in Serum [ Time Frame: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30,30+ (Day 30 + 3 to 6 hours), 31, 33 and 37. ] [ Designated as safety issue: No ]
    Concentrations of IFN-g, IL-1 beta (IL-1B), IL-5, IL-6, IL-10, Tumor Necrosis Factor-alpha (TNF-a), IFN-g-inducible protein-10 (IP-10) and monocyte chemotactic protein (MCP)-1 Concentrations of the IFN-g, IL-1B, IL-5, IL-6, IL-10, TNF-a, IP-10 and MCP-1 cytokines in serum were measured by Cytokine bead assay (CBA) and expressed in picograms per milliliter (pg/mL). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Normalized Levels of White Blood Cells (WBC) and Creatine Phosphokinases (CPK) [ Time Frame: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33, 37 and 60. ] [ Designated as safety issue: No ]
    Analysis of levels of CPK and WBC was performed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. Levels are presented as normalized levels vs. the IH center. Normalization was performed as follows: (Raw result - lower limit normal (LLN) at the IH center) divided by (Upper Limit Normal (ULN) at the IH center minus LLN at the IH center). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Normalized Levels of C-reactive Protein (CRP) [ Time Frame: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33 and 37. ] [ Designated as safety issue: No ]
    Analysis of levels of CRP was performed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. Levels are presented as normalized levels vs. the IH center. Normalization was performed as follows: (Raw result - lower limit normal (LLN) at the IH center) divided by (Upper Limit Normal (ULN) at the IH center minus LLN at the IH center). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Normalized Levels of White Blood Cells (WBC) and of Creatine Phosphokinases (CPK) [ Time Frame: At Days 0, 30, 37 and 60. ] [ Designated as safety issue: No ]
    Analysis of levels of CPK and WBC was performed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. Levels are presented as normalized levels vs. the IH center. Normalization was performed as follows: (Raw result - lower limit normal (LLN) at the IH center) divided by (Upper Limit Normal (ULN) at the IH center minus LLN at the IH center). This outcome measure concerns all subjects except subjects part of the HLA Subsets 1 and 2.

  • Normalized Levels of C-reactive Protein (CRP) [ Time Frame: At Days 0, 30 and 37. ] [ Designated as safety issue: No ]
    Analysis of levels of CRP was performed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. Levels are presented as normalized levels vs. the IH center. Normalization was performed as follows: (Raw result - lower limit normal (LLN) at the IH center) divided by (Upper Limit Normal (ULN) at the IH center minus LLN at the IH center). This outcome measure concerns all subjects except subjects part of the HLA Subsets 1 and 2.

  • Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils [ Time Frame: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33, 37 and 60. ] [ Designated as safety issue: No ]
    Levels of white blood cells (WBC) as absolute counts, neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS) and basophils (BAS) were assessed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. This outcome measure presents the raw data collected in percent (%), expressed in IH Center normalized levels based on raw data in % (IH normalized %), and concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils and Basophils [ Time Frame: At Days 0, 30, 37 and 60. ] [ Designated as safety issue: No ]
    Levels of white blood cells (WBC) as absolute counts, neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS) and basophils (BAS) were assessed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. This outcome measure presents the raw data collected in percent (%), expressed in IH Center normalized levels based on raw data in % (IH normalized %), and concerns all subjects except subjects part of the HLA Subsets 1 and 2.

  • Normalized Levels of Red Blood Cells and Platelets [ Time Frame: At Days 0, 30, 37 and 60. ] [ Designated as safety issue: No ]
    Analysis of levels of red blood cells (RBC) and platelets (PLA) were assessed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. Levels are presented as normalized levels vs. the IH center. Normalization was performed as follows: (Raw result - lower limit normal (LLN) at the IH center) divided by (Upper Limit Normal (ULN) at the IH center minus LLN at the IH center). This outcome measure presents the raw data collected in absolute count, expressed in IH Center normalized levels based on absolute count data (IH normalized abs. count).

  • Normalized Levels of Haemoglobin, Alanine Aminotransferase and Aspartate Aminotransferase [ Time Frame: At Days 0, 30, 37 and 60. ] [ Designated as safety issue: No ]
    Analysis of levels of haemoglobin (Hgb), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assessed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. Levels are presented as normalized levels vs. the IH center. Normalization was performed as follows: (Raw result - lower limit normal (LLN) at the IH center) divided by (Upper Limit Normal (ULN) at the IH center minus LLN at the IH center). This outcome measure presents the raw data collected in absolute count, expressed in IH Center normalized levels based on absolute count data (IH normalized abs. count).

  • Normalized Levels of Serum Creatinine, Urea and Lactate Dehydrogenase [ Time Frame: At Days 0, 30, 37 and 60. ] [ Designated as safety issue: No ]
    Analysis of levels of serum creatinine (S-CREA), urea and lactate dehydrogenase (LDH) were assessed with reference to the range observed at the Immune Health (IH) Centre in La Louvière, Belgium. Levels are presented as normalized levels vs. the IH center. Normalization was performed as follows: (Raw result - lower limit normal (LLN) at the IH center) divided by (Upper Limit Normal (ULN) at the IH center minus LLN at the IH center). This outcome measure presents the raw data collected in absolute count, expressed in IH Center normalized levels based on absolute count data (IH normalized abs. count).

  • Number of Subjects With Normal and Abnormal Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, C-reactive Protein, and Creatine Phosphokinase. [ Time Frame: At Day 0 and up to Day 60. ] [ Designated as safety issue: No ]
    Subjects were assessed with regard to their normal (Nor.) and abnormal (Abn.) levels for the above parameters of white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), basophils (BAS), C-reactive protein (CRP) and creatine phosphokinase (CPK) at the Day 0 baseline versus their status post vaccination (Day 60). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Subjects With Normal and Abnormal Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, C-reactive Protein, and Creatine Phosphokinase. [ Time Frame: At Day 0 and up to Day 60. ] [ Designated as safety issue: No ]
    Subjects were assessed with regard to their normal (Nor.) and abnormal (Abn.) levels for the above parameters of white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), basophils (BAS), C-reactive protein (CRP) and creatine phosphokinase (CPK) at the Day 0 baseline versus their status post vaccination (Day 60). This outcome measure concerns all subjects except subjects part of the HLA Subsets 1 and 2.

  • Number of Subjects With Normal and Abnormal Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, C-reactive Protein, and Creatine Phosphokinase. [ Time Frame: Post vaccination (up to Day 360) ] [ Designated as safety issue: No ]
    Subjects were assessed with regard to their normal (Nor.) and abnormal (Abn.) levels for the above parameters of white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), basophils (BAS), C-reactive protein (CRP) and creatine phosphokinase (CPK) at the Day 0 baseline versus their status post vaccination (Day 180 or 360). Day 180 or 360 results were chosen based on assessment of grading of the abnormality observed, with results for higher grading being tabulated.

  • Number of Subjects With Normal and Abnormal Levels of White Blood Cells, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils, C-reactive Protein, and Creatine Phosphokinase. [ Time Frame: At Days 360 and 390. ] [ Designated as safety issue: No ]
    Subjects were assessed with regard to their normal (Nor.) and abnormal (Abn.) levels for the above parameters of white blood cells (WBC), neutrophils (NEU), lymphocytes (LYM), monocytes (MON), eosinophils (EOS), basophils (BAS), C-reactive protein (CRP) and creatine phosphokinase (CPK) at the Day 360 baseline versus their status post vaccination (Day 390). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Subjects With Normal and Abnormal Levels of Red Blood Cells, Platelets, Haemoglobin, Alanine Aminotransferase, Aspartate Aminotransferase, Serum Creatinine, Urea and Lactate Dehydrogenase [ Time Frame: At Day 0 and up to Day 60. ] [ Designated as safety issue: No ]
    Subjects were assessed with regard to their normal (Nor.) and abnormal (Abn.) levels for the above parameters of red blood cells (RBC), platelets (PLA), haemoglobin (HGB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (S-CREA), urea and lactate dehydrogenase (LDH) at the Day 0 baseline versus their status post vaccination (Day 60).

  • Number of Subjects With Normal and Abnormal Levels of Red Blood Cells, Platelets, Haemoglobin, Alanine Aminotransferase, Aspartate Aminotransferase, Serum Creatinine, Urea and Lactate Dehydrogenase [ Time Frame: post vaccination (up to Day 360). ] [ Designated as safety issue: No ]
    Subjects were assessed with regard to their normal (Nor.) and abnormal (Abn.) levels for the above parameters of red blood cells (RBC), platelets (PLA), haemoglobin (HGB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (S-CREA), urea and lactate dehydrogenase (LDH) at the Day 0 baseline versus their status post vaccination (Day 180 or 360). Day 180 or 360 results were chosen based on assessment of grading of the abnormality observed, with results for higher grading being tabulated.

  • Number of Subjects With Normal and Abnormal Levels of Red Blood Cells, Platelets, Haemoglobin, Alanine Aminotransferase, Aspartate Aminotransferase, Serum Creatinine, Urea and Lactate Dehydrogenase [ Time Frame: At Days 360 and 390. ] [ Designated as safety issue: No ]
    Subjects were assessed with regard to their normal (Nor.) and abnormal (Abn.) levels for the above parameters of red blood cells (RBC), platelets (PLA), haemoglobin (HGB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (S-CREA), urea and lactate dehydrogenase (LDH) at the Day 360 baseline versus their status post vaccination (Day 390). This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited Local Symptoms Following Primary Vaccination. [ Time Frame: Within the 14-day (Days 0-13) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccines. ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling. All solicited local symptoms were considered as related to study vaccination. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling above (>) 50 millimeters (mm). Occurrence of a solicited local symptoms collected post-vaccination was a priori considered as related to vaccination.

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Following Primary Vaccination. [ Time Frame: Within the 14-day (Days 0-13) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccine. ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were Fatigue, Fever - oral temperature equal to or above (>=) 37.5 degrees Celsius (°C) -, Gastrointestinal symptoms (Gastr.), Headache, Malaise and Myalgia. Any = occurrence of a general symptom regardless of its intensity grade or relationship to vaccination. Related = occurrence of a general symptom assessed by the investigator to be causally related to vaccination. Grade 3 fever = oral temperature above (>) 39.0 °C. Grade 3 for Gastr., Headache, Malaise and Myalgia = occurrence of the specified solicited general symptom which prevented normal activity.

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited Local Symptoms Following Booster Vaccination. [ Time Frame: Within the 7-day (Days 0-6) follow up period following booster vaccination with HBsAg antigens ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed were pain, redness and swelling. All solicited local symptoms were considered as related to study vaccination. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling above (>) 50 millimeters (mm). Occurrence of a solicited local symptoms collected post-vaccination was a priori considered as related to vaccination. This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms Following Booster Vaccination. [ Time Frame: Within the 7-day (Days 0-6) follow up period following booster vaccination with HBsAg antigens ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed were Fatigue, Fever - oral temperature equal to or above (>=) 37.5 degrees Celsius (°C) -, Gastrointestinal symptoms (Gastr.), Headache, Malaise and Myalgia. Any = occurrence of a general symptom regardless of its intensity grade or relationship to vaccination. Related = occurrence of a general symptom assessed by the investigator to be causally related to vaccination. Grade 3 fever = oral temperature above (>) 39.0 °C. Grade 3 for Gastr., Headache, Malaise and Myalgia = occurrence of the specified solicited general symptom which prevented normal activity. This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Subjects Reporting Any, Grade 3 and/or Related Unsolicited Adverse Events (AEs) Following Primary Vaccination [ Time Frame: Within the 31-day (Days 0-30) follow up period following primary vaccination with the GSK223192A, Fendrix™ or Engerix-B™ vaccine ] [ Designated as safety issue: No ]
    An unsolicited AE was defined as an 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. Any = occurrence of an AE regardless of intensity grade or relationship to study vaccination. Grade 3 = occurrence of an AE that prevented normal activity. Related = occurrence of an AE assessed by the investigators as causally related to the study vaccine.

  • Number of Subjects Reporting Any, Grade 3 and/or Related Unsolicited Adverse Events (AEs) Following Booster Vaccination [ Time Frame: Within the 31-day (Days 0-30) follow up period following booster vaccination with HBsAg antigens ] [ Designated as safety issue: No ]
    An unsolicited AE was defined as an 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. Any = occurrence of an AE regardless of intensity grade or relationship to study vaccination. Grade 3 = occurrence of an AE that prevented normal activity. Related = occurrence of an AE assessed by the investigators as causally related to the study vaccine. This outcome measure concerns solely subjects part of the HLA Subsets 1 & 2 who received the Day 360 booster dose of HBsAg.

  • Number of Subjects Reporting Any and Related Adverse Events of Specific Interest (AESIs) [ Time Frame: During the entire study period, from Day 0 to study end, at Day 360 for subjects not in Subsets 1 & 2 and at Day 390 for subjects in Subsets 1 & 2. ] [ Designated as safety issue: No ]
    AESIs included Autoimmune Disease (AID), neurological/demyelinating events, rheumatic and connective diseases, autoimmune endocrine diseases, inflammatory bowel diseases, autoimmune blood disorders, inflammatory skin disorders, and other autoimmune/inflammatory events. Any AESI(s) = occurrence of any AESI(s) in a subject regardless of assessment of relationship to study vaccination. Related AESI(s) = Occurrence of AESI(s) in a subject assessed by the investigator as causally related to the study vaccination.

  • Number of Subjects Reporting Any Serious Adverse Events (SAEs) and SAEs Related to Study Vaccination [ Time Frame: During the entire study period, from Day 0 to study end, at Day 360 for subjects not in Subsets 1 & 2 and at Day 390 for subjects in Subsets 1 & 2. ] [ Designated as safety issue: No ]
    A SAE was defined as a medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any SAE(s) = occurrence of SAE(s) in a subject regardless of assessment of relationship to study vaccination. Related SAE(s) = occurrence of occurrence of SAE(s) in a subject assessed by the investigators as causally related to the study vaccination.

  • Gene Expression Signature Related to the Immune Response to the GSK223192A, Fendrix™ and Engerix-B™ Vaccines. [ Time Frame: At Days 0, 0+ (Day 0 + 3 to 6 hours), 1, 30, 30+ (Day 30 + 3 to 6 hours), 31, 33 and 37. ] [ Designated as safety issue: No ]
    Gene expression signature related to the immune response to the GSK223192A, Fendrix™ and Engerix-B™ vaccines will be measured by microarray/Polymerase Chain Reaction (PCR) array/quantitative PCR, using whole blood. This outcome will be assessed in the first 140 subjects in Subsets 1 and 2 recruited at the Immune Health (IH) Centre in La Louvière, Belgium. Results for this outcome measure will be posted when available.


Enrollment: 713
Study Start Date: December 2008
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK223192A 1 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 1, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: GSK Biologicals' Hepatitis B vaccines (GSK223192A)
2 doses intramuscular injections 3 different formulations of (GSK223192A), each administered to 1 group
Biological: HBsAg (Booster injection)
Single dose intramuscular injection
Experimental: GSK223192A 2 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 2, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: GSK Biologicals' Hepatitis B vaccines (GSK223192A)
2 doses intramuscular injections 3 different formulations of (GSK223192A), each administered to 1 group
Biological: HBsAg (Booster injection)
Single dose intramuscular injection
Experimental: GSK223192A 3 Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of GSK223192A vaccine, lot 3, at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The GSK223192A vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: GSK Biologicals' Hepatitis B vaccines (GSK223192A)
2 doses intramuscular injections 3 different formulations of (GSK223192A), each administered to 1 group
Biological: HBsAg (Booster injection)
Single dose intramuscular injection
Experimental: Fendrix Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Fendrix™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Fendrix™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: Fendrix™
2 doses intramuscular injections
Biological: HBsAg (Booster injection)
Single dose intramuscular injection
Active Comparator: Engerix-B Group
Subjects aged between, and including, 18 and 45 years at the time of first vaccination received 2 doses of Engerix-B™ vaccine at Days 0 and 30. 2 subsets of subjects within the group - subjects identified with either a pre-defined Human Leukocytes Antigen (HLA) Class I subtype (Subset 1) or a pre-defined HLA Class II subtype (Subset 2) - additionally received 1 booster dose of Hepatitis B surface antigens (HBsAg) at Day 360. The Engerix-B™ vaccine and HBsAg antigens were administered intramuscularly into the deltoid muscle of the non-dominant arm.
Biological: Engerix-B™
2 doses intramuscular injections
Biological: HBsAg (Booster injection)
Single dose intramuscular injection

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry :

  • Subjects who the investigator believes that they can and will comply with the requirements of the protocol.
  • A male or female between, and including, 18 and 45 years at the time of the first vaccination.
  • Written informed consent obtained from the subject.
  • Healthy subjects as established by medical history, clinical examination and clinical laboratory assessment before entering into the study.
  • If the subject is female, she must be of non-childbearing potential, or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series.

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:

  • Previous vaccination against Hepatitis B.
  • Positive for anti-HBs antibodies, antiHBc antibodies, HBsAg, HCV antibodies and/or HIV.
  • Any previous administration of specific adjuvant components.
  • Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period or participation to another pharmaceutical/vaccine study.
  • Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.
  • Planned administration/ administration of a vaccine not foreseen by the study protocol within 30 days of the first dose of vaccine with the exception of the influenza vaccine (pandemic or seasonal) which can be administered > 21 days preceding or > 21 days following each primary vaccine dose (Doses 1 and 2) AND > 7 days preceding or > 7 days following the booster dose.
  • Administration of immunoglobulins and/or any blood products within the last 3 months.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
  • History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
  • Current serious neurologic or mental disease.
  • Any past or current malignancies and lymphoproliferative disorders.
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal functional abnormality, autoimmune disease or anemia, as determined by physical examination or laboratory screening tests at the discretion of the investigator.
  • Acute disease at the time of enrolment.
  • Pregnant or lactating female.
  • History of chronic alcohol consumption and/or drug abuse.
  • Other conditions that the principal investigator judges may interfere with study findings.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00805389

Locations
Belgium
GSK Investigational Site
Bruxelles, Belgium, 1200
GSK Investigational Site
Gent, Belgium, 9000
GSK Investigational Site
La Louvière, Belgium, 7100
GSK Investigational Site
Wilrijk, Belgium, 2610
Germany
GSK Investigational Site
Tuebingen, Baden-Wuerttemberg, Germany, 72074
GSK Investigational Site
Haag, Bayern, Germany, 83527
GSK Investigational Site
Muenchen, Bayern, Germany, 81241
GSK Investigational Site
Muenchen, Bayern, Germany, 80636
GSK Investigational Site
Regensburg, Bayern, Germany, 93053
GSK Investigational Site
Wuerzburg, Bayern, Germany, 97070
GSK Investigational Site
Mainz, Rheinland-Pfalz, Germany, 55131
GSK Investigational Site
Berlin, Germany, 12627
GSK Investigational Site
Berlin, Germany, 13125
GSK Investigational Site
Hamburg, Germany, 20253
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00805389     History of Changes
Other Study ID Numbers: 112115
Study First Received: December 5, 2008
Results First Received: December 19, 2012
Last Updated: February 12, 2015
Health Authority: Belgium: Agence Fédérale des Médicaments et des Produits de la Santé
Germany: Paul-Ehrlich-Institut

Keywords provided by GlaxoSmithKline:
Adjuvant Systems
Hepatitis B

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
DNA Virus Infections
Digestive System Diseases
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on August 27, 2015