A Study to Evaluate the Safety and Immunogenicity of GlaxoSmithKline's Herpes Zoster Subunit Vaccine (HZ/su) When Given on a Two-dose Schedule to Adults at Least 50 Years of Age (YOA) Who Had Prior Episode of Shingles

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and immunogenicity of GSK Biologicals' HZ/su vaccine when given on a two-dose schedule to adults aged 50 years and above who have had a previous episode of shingles.

Detailed Description
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The study will be conducted in 2 epochs: Epoch 001- starting from visit day 1, followed by visit month 2 and then Visit 3 at one month post last vaccination (Month 3). Epoch 002- Starting with monthly contact after Visit 3 (Month 3) and ending at 26 months from the enrolment date.

Official Title
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A Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Subunit Vaccine (HZ/su) GSK1437173A on a Two-dose Schedule in Adults ≥ 50 Years of Age With a Prior Episode of Herpes Zoster

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: Herpes Zoster subunit (HZ/su) vaccine (GSK1437173A)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects and/or subject's LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol Written informed consent obtained from the subject/subject's LAR(s) prior to performance of any study specific procedure. A male or female ≥ 50 YOA at the time of the first vaccination. Subjects with a history of HZ. Confirmation of the prior HZ diagnosis can be done by one of the following three methods: Clinically diagnosed HZ: OR Laboratory diagnosed HZ: OR HZ diagnosed by an adjudication committee: Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy, bilateral salpingectomy or post-menopause. • Female subjects of childbearing potential may be enrolled in the study if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception for 2 months after completion of the vaccination series. Exclusion Criteria: Subjects who at time of study entry or during the maximum period of anticipated study participation are/will become part of the population recommended to receive a zoster vaccine per existing local or national immunization practices will be excluded from study participation. Use of any investigational or non-registered product other than the study vaccine during the period starting 30 days before the first dose of study vaccine, or planned use during the study period. Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe. Onset of HZ in the past 6 months or any ongoing symptoms from a prior HZ episode. Chronic antiviral use for HZ prophylaxis. History of >1 prior episode of HZ. A history of disseminated HZ, cutaneous or associated with visceral disease or associated with neurologic disease caused by VZV infection. 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, long-acting immune-modifying agents or immunosuppressive/cytotoxic therapy Administration or planned administration of a vaccine not foreseen by the study protocol within the period starting 30 days before the first dose of study vaccine and ending 30 days after the last dose of study vaccine. However, licensed pneumococcal vaccines and non-replicating vaccines may be administered up until 8 days prior to dose 1 and/or dose 2 and/or at least 14 days after any dose of study vaccine. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product Previous vaccination against VZV or HZ. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine. Acute disease and/or fever at the time of enrolment. Administration of immunoglobulins and/or any blood products during the period starting 3 months before the first dose of study vaccine or planned administration during the study period. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions in the period up to 2 months after completion of the vaccination series.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HZ/su Group<br>Subjects randomized to the HZ/su group will receive 2 doses of HZ/su vaccine at visit day 1 and visit month 2 and will be followed up until the study end. | Biological: Herpes Zoster subunit (HZ/su) vaccine (GSK1437173A)<br>* 2 doses of the HZ/su vaccine in a 0,2 Months schedule, administered intramuscularly<br>|
| Placebo Comparator: Placebo Group<br>Subjects randomized to Placebo group will receive placebo at visit day 1 and visit month 2 and will be followed up until the study end. | Drug: Placebo<br>* 2 doses of the placebo in a 0,2 Months schedule, administered intramuscularly<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of confirmed Herpes Zoster (HZ) cases | A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A suspected case of HZ is confirmed by 2 ways: - By PCR (Polymerase Chain Reaction). - By the HZ Ascertainment Committee (HZAC). The incidence of HZ recurrence in the HZ/su group versus placebo group is compared by performing a non-inferiority analysis. | From one-month post-dose 2 (i.e. Month 3) to study end (i.e. Month 26) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of confirmed HZ cases | A suspected case of HZ is defined as a new unilateral rash accompanied by pain and no alternative diagnosis. A suspected case of HZ is confirmed by 2 ways: - By PCR (Polymerase Chain Reaction). - By the HZ Ascertainment Committee (HZAC). | From Visit Day 1 till study end (Month 26) | 
| Number of subjects with any solicited local adverse events (AEs) | An AE is 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. Assessed solicited local AEs are pain, redness swelling and itching at the injection site. Any = occurrence of the AE regardless of intensity grade. | Within 7 days after each vaccination (Vaccines administered on Day 1 and Month 2) | 
| Number of subjects with any solicited general adverse events (AEs) | An AE is 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. Assessed solicited general AEs are fatigue, fever (defined as axillary temperature ≥ 38.0°C / 100.4°F), gastrointestinal symptoms, headache, myalgia, shivering and malaise. Any = occurrence of the AE regardless of intensity grade. | Within 7 days after each vaccination (Vaccines administered on Day 1 and Month 2) | 
| Number of subjects with any unsolicited 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. Any is defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. | Within 30 days after each vaccination (Vaccines administered on Day 1 and Month 2) | 
| Number of subjects with any serious adverse events (SAEs) | SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any= occurrence of SAE regardless of the relation to vaccination. | From Visit Day 1 up to 30 days post last vaccination (i.e. Month 3) | 
| Number of subjects with any serious adverse events (SAEs) | SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any= occurrence of SAE regardless of the relation to vaccination. | From 30 days post last vaccination (i.e. Month 3) to 1 year post last vaccination (i.e. Month 14) | 
| Number of subjects with any related SAEs | SAEs assessed include any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Related= Any SAE related to investigational vaccine or related to study participation or to a GSK concomitant medication/vaccine as assessed by the investigator. | During the entire study period (Visit day 1 to Month 26) | 
| Number of subjects with any potential immune-mediated diseases (pIMDs). | 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. Any= occurrence of pIMD regardless of intensity grade and relationship to the vaccination. | From Visit Day 1 up to 30 days post last vaccination (i.e. Month 3) | 
| Number of subjects with any pIMDs. | 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. Any= occurrence of pIMD regardless of intensity grade and relationship to the vaccination | From 30 days post last vaccination (i.e. Month 3) to 1 year post last vaccination (i.e. Month 14) | 
| Vaccine response rate (VRR) for anti-glycoprotein E (Anti-gE) antibodies as determined by Enzyme Linked Immunosorbent Assay (ELISA) | VRR is defined as percentage of subjects who have at least: - A 4-fold increase in the post last vaccination anti-gE Ab concentration as compared to the pre-vaccination anti-gE Ab concentration, for subjects who are seropositive at baseline, or, - A 4-fold increase in the post last vaccination anti-gE Ab concentration as compared to the anti-gE Ab cut-off value for seropositivity, for subjects who are seronegative at baseline. | At Month 2 and Month 3 | 
| Anti-gE antibody concentrations in terms of Geometric Mean Concentrations (GMCs) as determined by ELISA | The geometric mean concentration (GMC) calculations are performed by taking the antilog of the mean of the log concentration transformations. | At Day 1, Month 2 and Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Shingles, Shingles recurrence, HZ, Vaccine response rate