Study to Evaluate Efficacy, Safety, and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Vaccine GSK1437173A

A suspected case of HZ was defined as (1) a new rash characteristic of HZ (e.g., unilateral, dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or other sensations), or a vesicular rash suggestive of VZV infection regardless of the distribution, and no alternative diagnosis; or (2) a clinical presentation (symptoms and/or signs) and specific laboratory findings\* suggestive of VZV infection in the absence of characteristic HZ or VZV rash. A suspected case of HZ was confirmed either: by Polymerase Chain Reaction (PCR) or by the HZ Ascertainment Committee (HZAC), consisting of physicians with HZ expertise.

Time frame: From Month 0 until the cut-off date for final analysis (median follow-up was of 21 months)

Population: The analysis was performed on the modified Total Vaccinated Cohort, which excluded subjects from the Total Vaccinated Cohort analysis who were not administered with the second vaccination or who received vaccine doses/or replacement not on the same group or who developed a confirmed case of HZ prior to 1 month after the second vaccination.

Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seropositivity cut-off value was greater than or equal to (≥) 97 mIU/mL.

Time frame: At Months 0, 1, 2, 13 and 25

Population: The analysis was performed on the adapted According-to-Protocol (ATP) cohort for humoral immunogenicity, which included data from the ATP cohorts for humoral immunogenicity at Months 0,1,2,13 and 25. The ATP cohort for humoral immunogenicity included all subjects from humoral immunogenicity sub-cohort in ATP cohort for analysis of immunogenicity.

Duration of HZ-associated pain rated as 3 or greater on the 'worst pain' Zoster Brief Pain Inventory (ZBPI) question, following the onset of a confirmed HZ rash over the entire pain reporting period in subjects with confirmed HZ; presented as T (day) \[=the sum of follow-up period (for subjects without severe worst pain T is 1, for subjects with severe worst pain T is the duration of severe worst pain) expressed in days\].

Time frame: From Month 0 until study end (4 years approximately), from the onset of a confirmed HZ rash over the entire pain reporting period

Population: The analysis was performed on the modified Total Vaccinated Cohort, which excluded subjects from the Total Vaccinated Cohort analysis, who developed a confirmed case of HZ prior to 1 month after the second vaccination.

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

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with respect to the vaccine actually administered, who had filled in their symptom sheets.

Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.

Time frame: From Month 0 up to 365 days post last vaccination

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with respect to the vaccine actually administered.

Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, headache, myalgia, shivering and fever \[defined as axillary/tympanic temperature equal to or above 37.5 degrees Celsius (°C) or rectal temperature equal to or above 38.0 °C\]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.5 °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

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with respect to the vaccine actually administered, who had filled in their symptom sheets.

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

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with respect to the vaccine actually administered.

Relapse was defined as the occurrence of the underlying malignancy or disease for which the HCT was undertaken.

Time frame: From Month 0 until study end (approximate median of 29 months follow-up - minimum 1 year and maximum 4 years)

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with respect to the vaccine actually administered.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. This enpoint also presents SAES related to the GSK study vaccine/placebo.

Time frame: From Month 0 until 365 days post last vaccination (approximate median of 29 months follow-up - minimum 1 year and maximum 4 years)

Population: The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects with respect to the vaccine actually administered.

This analysis excluded complications that were linked to a confirmed HZ case that occurred after the start of the relapse treatment.

Time frame: From Month 0 until the cut-off date for final analysis (median follow-up was of 21 months)

Population: The analysis was performed on the modified Total Vaccinated Cohort, which excluded subjects from the Total Vaccinated Cohort analysis who were not administered with the second vaccination or who received vaccine doses/or replacement not on the same group or who developed a confirmed case of HZ prior to 1 month after the second vaccination.

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. This endpoint presents fatal SAEs and SAEs related to study participation or to a concurrent GSK medication/vaccine.

Time frame: From the Pre-vaccination visit (Up to 110 days prior Month 0) until study end (approximate median of 29 months follow-up minimum 1 year and maximum 4 years)

Population: The analysis was performed on the Total Enrolled Cohort.

This analysis excluded PHN episodes that were linked to a confirmed HZ case that occurred after the start of the relapse treatment.

Time frame: From Month 0 until study end (21 months median follow-up)

Population: The analysis was performed on the modified Total Vaccinated Cohort, which excluded subjects from the Total Vaccinated Cohort analysis who were not administered with the second vaccination or who received vaccine doses/or replacement not on the same group or who developed a confirmed case of HZ prior to 1 month after the second vaccination.