Based on the results of a previous clinical PhaseI/II study, GSK1437173A is the lead GSK candidate Herpes Zoster (HZ) vaccine to prevent episodes of HZ (shingles). This phase II study will be subdivided into a primary study (108494) and three extension studies (108516, 108518 \& 108520), consisting of one additional visit each at months 12, 24 and 36, respectively, from the first visit of the Zoster-003 primary study onwards. The aim of the primary 108494 study is to evaluate the immunogenicity \& safety of different dosages of the GSK1437173A vaccine in healthy elderly population. The study population will be stratified by age. The primary objective of this trial is to select the best dosage of GSK1437173A. The aim of the extension studies is to evaluate the persistence of the immune response induced by the candidate HZ vaccine during a long term period. No new subjects will be enrolled during the extension phases of the study.
The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
715
Single or two-dose intramuscular injection.
Single or two-dose intramuscular injection.
Single or two-dose intramuscular injection.
Single or two-dose intramuscular injection.
Single intramuscular injection
GSK Investigational Site
Hradec Králové, Czechia
GSK Investigational Site
Mannheim, Baden-Wurttemberg, Germany
GSK Investigational Site
Würzburg, Bavaria, Germany
GSK Investigational Site
Hanover, Lower Saxony, Germany
GSK Investigational Site
Cologne, North Rhine-Westphalia, Germany
GSK Investigational Site
Essen, North Rhine-Westphalia, Germany
GSK Investigational Site
Berlin, Germany
GSK Investigational Site
Amsterdam, Netherlands
GSK Investigational Site
Rotterdam, Netherlands
GSK Investigational Site
Eskilstuna, Sweden
...and 1 more locations
Frequency of Glycoprotein E (gE)-Specific Cluster of Differentiation (CD4) T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 \[IL-2\] and/or interferon-gamma \[IFN-γ\] and/or tumour necrosis factor-alpha \[TNF-α\] and/or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects aged 70 or higher (≥).
Time frame: One month after the second vaccination (Month 3)
Frequency Odds Ratio of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 \[IL-2\] and/or interferon-gamma \[IFN-γ\] and/or tumour necrosis factor-alpha \[TNF-α\] and/or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects ≥ 70 years old. The odds-ratios are calculated using the the frequency of CD4 secreting cytokines, upon in vitro stimulation with the specific antigen, at the numerator and the frequency of the CD4 secreting cytokines with the medium only (background level) at the denominator. The odds-ratios represent the fold-change in the specific response compared to the background level.
Time frame: One month after the second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 \[IL-2\] and/or interferon-gamma \[IFN-γ\] and/or tumour necrosis factor-alpha \[TNF-α\] and/or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects ≥ 70 years old.
Time frame: One month after the second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 \[IL-2\] and/or interferon-gamma \[IFN-γ\] and/or tumour necrosis factor-alpha \[TNF-α\] and/or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS) in subjects 60 to 69 years (60-69y) and ≥ 70 years (+70y) old.
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing IFN-γ and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or tumour necrosis factor-alpha \[TNF-α\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing IL-2 and at Least Another Activation Marker
Among other activation markers expressed were interferon-gamma \[IFN-γ\] or tumour necrosis factor-alpha \[TNF-α\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing TNF-α and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or interferon-gamma \[IFN-γ\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4 T-cells Expressing CD40L and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or interferon-gamma \[IFN-γ\] or tumour necrosis factor-alpha \[TNF-α\] . Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 \[IL-2\] and/or interferon-gamma \[IFN-γ\] and/or tumour necrosis factor-alpha \[TNF-α\] and/or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or tumour necrosis factor-alpha \[TNF-α\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
Among other activation markers expressed were interferon-gamma \[IFN-γ\] or tumour necrosis factor-alpha \[TNF-α\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing TNF-α and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or interferon-gamma \[IFN-γ\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD8 T-cells Expressing CD40L and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or interferon-gamma \[IFN-γ\] or tumour necrosis factor-alpha \[TNF-α\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Anti-gE Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL), as assessed by ELISA.
Time frame: At pre-vaccination (Day 0), one month after the first vaccination (Month 2) and second vaccination (Month 3)
Frequency of gE-specific CD4/CD8 T-cells Expressing at Least Two Different Activation Markers
Among the activation markers expressed were interleukin-2 \[IL-2\] and/or interferon-gamma \[IFN-γ\] and/or tumour necrosis factor-alpha \[TNF-α\] and/or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Time frame: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing IFN-γ and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or tumour necrosis factor-alpha \[TNF-α\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Time frame: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing IL-2 and at Least Another Activation Marker
Among other activation markers expressed were interferon-gamma \[IFN-γ\] or tumour necrosis factor-alpha \[TNF-α\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Time frame: At Months 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing TNFα and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or interferon-gamma \[IFN-γ\] or cluster of differentiation 40-ligand \[CD40-L\]. Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Time frame: At Month 12, 24 and 36
Frequency of gE-specific CD4/CD8 T-cells Expressing CD40L and at Least Another Activation Marker
Among other activation markers expressed were interleukin-2 \[IL-2\] or interferon-gamma \[IFN-γ\] or tumour necrosis factor-alpha \[TNF-α\] . Analysis of cytokines expression was done by means of in vitro flow cytometry using intracellular cytokine staining (ICS). Month 12, 24 and 36 CMI analyses on CD8+ T cells were not performed as no detectable CD8 T+ cell response was measured to any of the vaccine formulations in the primary (108494) study.
Time frame: At Month 12, 24 and 36
Anti-gE Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).
Time frame: At Months 12, 24 and 36
Anti-varicella Zoster Virus (VZV) Specific Antibody Concentrations
Concentrations were presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL).
Time frame: At Months 12, 24 and 36
Frequency of VZV-specific Memory B-cells in a Subset of Subjects
Memory B cells specific to the gE antigen, as assessed by the enzyme-linked immunosorbent spot (ELISPOT) method, were expressed as a frequency of the specific memory B-cells per million memory B-cells. Results were tabulated for subjects aged 70 years and older.
Time frame: At pre-vaccination (Day 0) and at Month 3
Number of Subjects With Different Biochemical and Haematological Levels
Among biochemical and haematological parameters assessed were albumin \[ALB\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], basophils \[BAS\], calcium \[CAL\], eosinophils \[EOS\], fibrinogen \[FIB\], haematocrit \[HEM\], hemoglobin \[Hgb\], leucocytes \[LEU\], lymphocytes \[LYM\], lactate dehydrogenate \[LDH\], monocytes \[MON\], neutrophils \[NEU\], partial thromboplastin time \[PTPT\], platelets \[PLA\], pro thrombin time \[PTT\], red blood cells \[RBC\], serum creatinine \[SCREA\], total protein \[TP\]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - unknown, below, within and above.
Time frame: At Day 0, Month 2 and Month 3
Number of German Subjects With Different Biochemical and Haematological Levels
Among biochemical and haematological parameters assessed were albumin \[ALB\], calcium \[CAL\], fibrinogen \[FIB\], lactate dehydrogenase \[LDH\], partial thrombo-plastin time \[PTPT\], pro thrombin time \[PTT\], total protein \[TP\]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - below, within, above and missing, as compared to the pre-vaccination status (below, within, above or missing). Values for electrophoresis (globulins and albumin/globulin ratio) were not displayed.
Time frame: At one week post-vaccination 1 (Month 0)
Number of German Subjects With Different Biochemical and Haematological Levels
Among biochemical and haematological parameters assessed were albumin \[ALB\], calcium \[CAL\], fibrinogen \[FIB\], lactate dehydrogenase \[LDH\], partial thrombo-plastin time \[PTPT\], pro thrombin time \[PTT\], total protein \[TP\]. Levels of haematological/biochemical parameters assessed in terms of normal laboratory values were - below, within, above and missing, as compared to the pre-vaccination status (below, within, above or missing). Values for electrophoresis (globulins and albumin/globulin ratio) were not displayed.
Time frame: At one week post-vaccination 2 (Month 2)
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Assessed solicited general symptoms were arthralgia, fatigue, fever \[defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], headache and myalgia. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time frame: During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
Number of Subjects With Occurrence of Clinically Diagnosed Herpes Zoster (HZ) Episodes
Clinically diagnosed episodes included rash that was assessed by hives, idiopathic thrombocytopenic purpura, petechiae.
Time frame: From Month 0 to Month 3
Number of Subjects With Occurrence of Clinically Diagnosed HZ Episodes
Clinically diagnosed episodes included rash that was assessed by hives, idiopathic thrombocytopenic purpura, petechiae.
Time frame: From Month 3 up to Month 36
Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs)
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and 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 was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
Time frame: During the 30-day (Days 0-29) post-vaccination period
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time frame: From Month 0 to Month 3
Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Time frame: From Month 3 to Month 12
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