A Long-term Follow-up Study (ZOE-LTFU) of Two Studies 110390 (ZOSTER-006) and 113077 (ZOSTER-022) to Assess the Efficacy, Safety, and Immunogenicity Persistence of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine and Assessment of 1 or 2 Additional Doses in Two Subgroups of Older Adults

A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by Polymerase Chain Reaction (PCR) and/or by HZ Ascertainment Committee (HZAC) determination, as per the algorithm pre-specified in the protocol.

As pre-specified in the protocol:

• due to the high VE observed in ZOSTER-006/022 studies, recipients of placebo in both studies were offered cross-vaccination with HZ/su. Since there was no placebo group in this study, historic controls were used for VE assessment. Incidence rates estimations on Historical Control group were done by utilizing Poisson regression model using placebo data from ZOSTER-006/022 studies to obtain the coefficients by age ranges.
• the participants in Control group were a subset of LTFU group that were randomized to serve as control for those who were vaccinated in this study, otherwise they were treated similarly as LTFU group, hence LTFU and Control groups were combined.

A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by PCR and/or by the HZAC determination, as per the algorithm pre-specified in the protocol. The age ranges assessed were: 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by PCR and/or by the HZAC determination, as per the algorithm pre-specified in the protocol. The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

As pre-specified in the protocol:

• participants from the Placebo groups in the ZOSTER-006/022 studies for Year 1 through Year 4 preceding the ZOSTER-049 EXT:006-022 study start and from the hypothetical Historical control group in the ZOSTER-049:EXT 006-022 study for Year 6 and onwards were combined in the Placebo/Historical control group.

A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A confirmed case of HZ was diagnosed by PCR and/or by the HZAC determination, as per the algorithm pre-specified in the protocol. The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

Confirmed HZ cases data was not collected for the participants included in the HZ/su and Placebo/Historical control groups during Year 5, as this was a gap year between end of ZOSTER-006/-022 studies and start of ZOSTER-049:EXT-006-022 study.

Results from the ZOSTER-006/022 studies were pooled for each year after vaccination with methods used in these studies. For overlapping years between ZOSTER-006/022 studies and this study, all the data were pooled. For the non-overlapping years only the data from ZOSTER-049:EXT 006-022 study was used.

PHN is defined by the presence of HZ-associated severe worst pain persisting or appearing more than 90 days after onset of the HZ rash. Severe worst pain is defined as HZ-associated pain rated as 3 or greater on the worst pain question on the Zoster Brief Pain Inventory (ZBPI) questionnaire. The ZBPI questionnaire uses a 0 to 10 point numeric and visual intensity scale, in which 0 represents the minimum value and 10 the maximum value on the scale. The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

PHN is defined by the presence of HZ-associated severe worst pain persisting or appearing more than 90 days after onset of the HZ rash. Severe worst pain is defined as HZ-associated pain rated as 3 or greater on the worst pain question on the Zoster Brief Pain Inventory (ZBPI) questionnaire. The ZBPI questionnaire uses a 0 to 10 point numeric and visual intensity scale, in which 0 represents the minimum value and 10 the maximum value on the scale. The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

HZ complications include HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease, visceral disease or stroke. If a recorded complication was associated with a case of suspected HZ, and that case was finally not considered to be a confirmed case, the associated complication would not be considered as a complication of HZ. The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

HZ complications include HZ vasculitis, disseminated disease, ophthalmic disease, neurologic disease, visceral disease or stroke. If a recorded complication was associated with a case of suspected HZ, and that case was finally not considered to be a confirmed case, the associated complication would not be considered as a complication of HZ. The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs) in milli-international units per milliliter (mIU/mL). The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

Frequency of CD4 (2+) T-cells with antigen-specific Interferon gamma (IFN-γ) and/or Interleukin-2 (IL-2) and/or Tumour Necrosis Factor alpha (TNF-α) and/or CD40 Ligand (CD40L) secretion/expression to gE was determined by Intracellular Cytokine Staining (ICS) and expressed in CD4 (2+) T-cells/million cells. The age ranges assessed were: >=50 YOA (overall), 50-59 YOA, 60-69 YOA, >=60 YOA and >=70 YOA at time of primary vaccination in ZOSTER-006/022 studies.

Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.

Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.

Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.

Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.

Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.

Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.

Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.

Frequency of CD4 (2+) T-cells with antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L secretion/expression to gE was determined by ICS and expressed in CD4 (2+) T-cells/million cells.

The assessed solicited local symptoms included pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site.

Duration is the number of days in which a participant experienced the symptom within the 7-day solicited follow-up period. The assessed solicited local symptoms included pain, redness and swelling.

The assessed solicited general symptoms included fatigue, fever [defined as oral temperature >=37.5 degrees Celsius (°C)], gastrointestinal symptoms, headache, myalgia, and shivering. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. 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.

Duration is the number of days in which a participant experienced the symptom within the 7-day solicited follow-up period. The assessed solicited general symptoms included fatigue, fever [defined as oral temperature >=37.5°C], gastrointestinal symptoms, headache, myalgia, and shivering.

An unsolicited AE is defined as 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 = occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant. Any SAE = occurrence of the SAE regardless of intensity or relation to study vaccination. Related SAE = SAE assessed by the investigator as related to vaccination.

An SAE is defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant.

pIMDs are defined as 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. Any pIMDs = occurrence of a pIMD regardless of relation to vaccination. Related pIMD = a pIMD assessed by the investigator as related to the study vaccination.