Study to Evaluate Immunogenicity and Safety of GSK Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine at 9 and 10 Years After Vaccine Administration and Assessment of Re-vaccination With 2 Additional Doses at 10 Years After Initial Vaccination, in Healthy Subjects Aged 60 Years of Age(YOA) and Older

GlaxoSmithKline70 enrolled

Overview

The purpose of this study is to evaluate the persistence of immune response to the HZ vaccine as well as safety up to 10 years after the first dose of initial vaccination course. This study will also assess immune responses after re-vaccination with 2 additional doses of the HZ/su administered at ten years after first dose of initial vaccination course from study Zoster-003 (NCT00434577).

In this LTFU study (ZOSTER-060), subjects who received 2 doses of HZ/su in the earlier Zoster-003 (NCT00434577) study will be followed up at Month 108/Year 9 and Month 120/Year 10 post first dose of vaccine for safety and immunogenicity (humoral and cellular). In order to assess the effect of re-vaccination with 2 additional doses of HZ/su vaccine, all the subjects will receive 2 additional doses of the HZ/su vaccine, on a 0, 2-month schedule at ten years after the initial vaccination course in study Zoster-003 (NCT00434577), and will be followed for reactogenicity, safety and humoral and cellular immunogenicity (including persistence). In alignment with the previous persistence timepoints, this study has no control group.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Herpes Zoster

Interventions

Eligibility

Sex: ALLMin age: 68 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits, ability to have scheduled contacts to allow evaluation during the study). Or subjects with a caregiver who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the diary cards, vaccination visits, availability for follow-up contacts). * Written informed consent obtained from the subject prior to performance of any study specific procedure. * Previous participation in study ZOSTER-003 (NCT00434577), in group 50 µg gE / AS01B, and who completed the vaccination course (2 doses of HZ/su) in study ZOSTER-003 (NCT00434577). * Subjects are expected to enter the study (or complete Visit 1) as of the time they turn 108 months after first vaccination of previous vaccination course with HZ/su and not later than 111 months. Exclusion Criteria: * Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine during the period starting 30 days before the first study visit (Day -29 to Day 0), or planned use during the study period. * Use or anticipated use of immunosuppressants or immune-modifying drugs during the period starting six months prior to study start and during the whole study period. This includes chronic administration of corticosteroids (\>14 consecutive days of prednisone at a dose of ≥20 mg/day \[or equivalent\]), long-acting immune-modifying agents (e.g., infliximab) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). * Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus \[HIV\] infection). * Administration or planned administration of a live vaccine in the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine, or, administration or planned administration of a non-replicating vaccine\* within 8 days prior to or within 14 days after either dose of study vaccine. E.g., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines and pneumococcal conjugate vaccines. * Previous vaccination against HZ since initial vaccination in Zoster-003. * Administration of immunoglobulins and/or any blood products during the period starting 3 months before the study start, or planned administration during the study period. * History of previous HZ.

Outcomes

Primary Outcomes

Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations

Anti-glycoprotein E (gE) Ab concentrations were determined by Enzyme-Linked Immunosorbent Assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micro international units per milliliter (mIU/mL).

Time frame: At Month 108 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).

Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations

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

Time frame: At Month 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).

Frequencies of gE (Glycoprotein)-Specific Cluster of Differentiation (CD4) (2+) T-cells.

gE specific CD4 (2+) T-cells expressing at least 2 activation markers among IFN-γ, IL-2, TNF-α and CD40L, were determined by means of Intracellular Cytokine Staining (ICS) and expressed in T-cells/million cells.

Time frame: At Month 108 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).

Frequencies of gE (Glycoprotein)-Specific Cluster of Differentiation (CD4) (2+) T-cells.

gE specific CD4 (2+)T-cells expressing at least 2 activation markers among IFN-γ, IL-2, TNF-α and CD40L were determined by means of ICS and expressed in T-cells/million cells.

Time frame: At Month 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).

Secondary Outcomes

Anti-glycoprotein (gE) Specific Antibody (Ab) Concentrations by Each Age Category

Anti-gE Ab concentrations as determined by ELISA by each age category (60-69 years of age \[YOA\] and ≥70 YOA at the time of initial vaccination).Antibody concentrations were presented as GMCs and expressed in mIU/mL.

Time frame: At Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).

Frequencies of Antigen-specific CD4 (2+) T-cells by Each Age Category

Antigen specific CD4 (2+) T-cells as determined by means of ICS and expressed in T-cells/million cells, by each age category (60-69 YOA and ≥ 70 YOA at the time of initial vaccination).

Time frame: At Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).

Number of Subjects With Any Serious Adverse Events (SAEs) Related to Study Participation or to a Concurrent GSK Medication/Vaccine (Including GSK1437173A Administered During the Zoster-003 [NCT00434577] Study).

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: Between Months 108 and 120 post first dose of initial vaccination course in study Zoster-003 (NCT00434577).

Anti-gE Specific Antibody (Ab) Concentrations

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

Time frame: At 1 month post each re-vaccination dose (i.e. Month 121 and Month 123) and at 1 year post last re-vaccination dose (i.e., Month 134).

Frequencies of Antigen-specific CD4 (2+) T-cells, Post Re-vaccination Course.

Antigen specific CD4 (2+)T cells were determined by means of ICS and expressed in T-cells/million cells.

Time frame: At 1 month post each re-vaccination dose (i.e. Month 121 and Month 123) and at 1 year post last re-vaccination dose (i.e., Month 134).

Number of Subjects With Any and Grade 3 Solicited Local Symptoms.

Assessed solicited local symptoms included: pain, redness and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, prevented normal every day activities. Grade 3 redness/swelling = symptoms spreading beyond a surface of (\>) 100 millimeters (mm).

Time frame: Within 7 days (Days 0-6) after each vaccination and across doses, in the current study.

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms.

Assessed solicited general symptoms included: fatigue, gastrointestinal symptoms \[nausea, vomiting, diarrhoea and/or abdominal pain\], headache, myalgia, shivering and temperature \[higher than or equal to (≥) 37.5 degrees Celsius (°C) for axillary, oral or tympanic route\] and ≥38.0°C for rectal route. Grade 3 fatigue, gastrointestinal symptoms, headache, myalgia, shivering = symptoms that prevented normal activity. Grade 3 temperature = defined as fever higher than (\>) 39.0°C, regardless of the route used.

Time frame: Within 7 days (Days 0-6) after each vaccination and across doses, in the current study.

Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) According to the Medical Dictionary for Regulatory Activities (MedDRA) Classification in All Subjects.

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 is 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: Within 30 days (Days 0-29) after each vaccination in the current study.

Number of Subjects With Any, Related and Fatal SAEs.

SAEs assessed include medical occurrences that resulted in death, were life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity.

Time frame: From Dose 1 of re-vaccination (Month 120) until study end (Month 134).

Number of Subjects With Any and Related Potential Immune-mediated Diseases (pIMDs).

pIMDs assessed includes AEs that were autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology. Related pIMDs= pIMDs assessed by the investigator as related to the vaccination.