Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Subunit (HZ/su) Vaccine (GSK1437173A) in Adults ≥ 65 Years of Age With and Without Zostavax® Vaccination at Least 5 Years Earlier

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of GSK Biologicals' HZ/su vaccine in adults ≥ 65 years of age with and without Zostavax® vaccination at least 5 years earlier.

Detailed Description
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The study will evaluate two parallel groups of 200 adults ≥ 65 YOA; one group (Prev-Zvax) with a previous Zostavax® vaccination at least 5 years earlier, versus the other group without a previous Zostavax® vaccination (No prev-Zvax). The goal of this study is to generate immunogenicity, safety and reactogenicity data for the respective vaccines.

Official Title
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Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults ≥ 65 Years of Age With and Without Zostavax® Vaccination at Least 5 Years Earlier

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine (GSK 1437173A)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol. A male or female ≥ 65 years of age at the time of the first vaccination. Written informed consent obtained from the subject prior to performing any study specific procedure. For the No prev-Zvax group only: • No previous vaccination with Zostavax. For the Prev-Zvax group only: • Previous vaccination with Zostavax ≥ 5 calendar years earlier. Documentation indicating the date of previous Zostavax vaccination will be required. Exclusion Criteria: Previous vaccination with Zostavax < 5 calendar years earlier and/or anyone that ever received more than a single dose of Zostavax. Previous vaccination against VZV, administration of HZ/su vaccine or any other investigational or non-registered HZ vaccine (except Zostavax for the Prev-Zvax group). 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. Chronic administration (defined as > 14 consecutive days) of immunosuppressants or other immune-modifying drugs in the period starting 6 months prior to the first dose of vaccine. (For corticosteroids, a prednisone dose of < 20 mg/day, or equivalent, is allowed.) Inhaled, topical and intra-articular corticosteroids are allowed. Administration of long-acting immune-modifying drugs (e.g., infliximab) in the period starting 6 months prior to the first vaccine dose or expected administration at any time during the study period. 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 in the period starting 8 days prior to and ending 14 days after either dose of study vaccine. Current participation in or planned concurrent participation 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 product. Planned administration of an HZ vaccine (including an investigational or non-registered vaccine) other than the study vaccine during the entire study. History of HZ or any suspected HZ between the screening visit and Visit 1. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine/product. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., malignancy, human immunodeficiency virus [HIV] infection) or immunosuppressive/cytotoxic therapy (e.g., medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders). Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C (99.5°F) by oral route, axillary or tympanic setting, or ≥ 38.0°C/100.4°F on rectal setting. The recommended route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products in the period starting 3 months preceding the first dose of study vaccine or planned administration during the study period. Significant underlying illness that, in the opinion of the investigator, would be expected to prevent completion of the study. Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study. Any condition which, in the judgment of the investigator, would make intramuscular (IM) injection unsafe.

Ages Eligible for Study
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Minimum Age: 65 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1437173A Group<br>Subjects ≥ 65 years of age who received Zostavax vaccine ≥ 5 years earlier and received 2 doses of the HZ/su vaccine (first dose given at Month 0 and second dose given 2 months later) in this study. | Biological: GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine (GSK 1437173A)<br>* 2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.<br>|
| Active Comparator: Control Group<br>Subjects ≥ 65 years of age who never received Zostavax vaccine and received 2 doses of the HZ/su vaccine (first dose given at Month 0 and second dose given 2 months later) in this study. | Biological: GSK Biologicals Herpes Zoster subunit (HZ/su) vaccine (GSK 1437173A)<br>* 2 doses administered by intramuscular (IM) injection into the deltoid muscle of the non-dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-glycoprotein E (Anti-gE) Antibody (Ab) Concentrations | Varicella Zoster Virus (VZV) gE Ab.Immunoglobulin G (IgG) was determined by Enzyme Linked Immunosorbent Assay (ELISA). Concentrations are presented as geometric mean concentrations (GMCs), expressed in milliinternational units per millilitre (mIU/mL). Geometric mean antibody concentrations were adjusted for group-matching variable. | One month after dose 2, at Month 3 | 
| Number of Subjects With Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = Occurrence of the symptom regardless of its intensity grade. Grade 3 pain = Significant pain at rest that prevented normal everyday activities. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | During the 7-day (Days 0-6) period after each dose. | 
| Number of Days With Solicited Local Symptoms | Solicited local symptoms were assessed during the 7-day (Days 0-6) period after each dose. | During the 7-day (Days 0-6) period after each dose. | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (included nausea, vomiting, diarrhea and/or abdominal pain), headache, myalgia, shivering and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)] . Any = Occurrence of the symptom regardless of its 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. | During the 7-day (Days 0-6) period after each dose. | 
| Number of Days With Solicited General Symptoms | Solicited general symptoms were assessed during the 7-day (Days 0-6) period after each dose. | During the 7-day (Days 0-6) period after each dose. | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Symptoms (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. | During the 30-day (Days 0-29) period after each dose. | 
| Number of Subjects With Any and Related Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Related SAE = SAE assessed by the investigator as related to the vaccination. | From first vaccination (Month 0) up to 30 days post last vaccination (Month 3) | 
| 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. | From first vaccination (Month 0) up to 30 days post last vaccination (Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-gE Ab Concentrations | VZV gE IgG antibody concentrations were determined by ELISA. Concentrations are presented as geometric mean concentrations (GMCs), expressed in milliinternational units per millilitre (mIU/mL). | At Months 0, 1, 3 and 14. | 
| Frequencies of gE-specific Cluster of Differentiation 4 (CD4+) T-cells | gE-specific CD4+ T-cells, expressing at least two activation markers (from among interferon gamma [IFN-γ], interleukin-2 [IL-2], tumour necrosis factor alpha [TNF-α] and cluster of differentiation 40-ligand [CD40L]), as determined by in vitro Intracellular Cytokine Staining (ICS). | At Months 0, 1, 3 and 14. | 
| Number of Subjects With Any and Related SAEs | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Related SAE = SAE assessed by the investigator as related to the vaccination. | From 30 days post last vaccination (Month 3) until study end at Month 14 | 
| 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. | From 30 days post last vaccination (Month 3) until study end at Month 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zostavax®, ≥ 65 years of age, Herpes Zoster, Shingles, Immunogenicity, Safety