Safety and Immunogenicity of Different Dosing Schedules of GlaxoSmithkline (GSK) Biologicals' Herpes Zoster (HZ) Vaccine in Adults 50 Years of Age or Older

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 the GSK Biologicals' HZ vaccine 1437173A administered on either a 0,2-; 0,6- or 0,12-month schedule in adults aged 50 years or above, as the immunogenicity of the HZ vaccine administered at intervals longer than two months is not known.

Detailed Description
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Subjects in each group will be stratified by age with a minimum of 35 subjects in each stratum (50-59 years of age (YOA) stratum, 60-69 YOA stratum and ≥ 70 YOA stratum).

Official Title
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Open-label Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults Aged 50 Years or Older

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: Herpes zoster vaccine GSK1437173A


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 aged 50 years or older at the time of the first vaccination. Written informed consent obtained from the subject. Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy 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 during the entire treatment period and for two months after completion of the vaccination series. Exclusion Criteria: Use of any investigational or non-registered product other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, a prednisone dose of < 20 mg/day, or equivalent, is allowed. Inhaled, topical and intra-articular corticosteroids are allowed. Administration or planned administration of a live vaccine in the period starting 30 days before and ending 30 days after either dose of study vaccine. Administration or planned administration of a non-replicating vaccine within eight days prior to or within 14 days after either dose of study vaccine. Administration of long-acting immune-modifying drugs (e.g. infliximab) within six months prior to the first vaccine dose or expected administration at any time during the study period. Previous vaccination against varicella or HZ (either registered product or participation in a previous vaccine study). Planned administration during the study of an HZ or varicella vaccine (including an investigational or non-registered vaccine) other than the study vaccine. History of HZ. History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s). 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) for oral, axillary or tympanic route, or ≥ 38.0°C (100.4°F) for rectal route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within the three 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. Pregnant or lactating female. Female planning to become pregnant during the entire treatment period and for two months after completion of the vaccination series, or planning to discontinue contraceptive precautions (if of childbearing potential).

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HZ/su-0,2 Group<br>Subjects will receive HZ/su vaccine on a 0,2-month schedule. | Biological: Herpes zoster vaccine GSK1437173A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>|
| Experimental: HZ/su-0,6 Group<br>Subjects will receive HZ/su vaccine on a 0,6-month schedule. | Biological: Herpes zoster vaccine GSK1437173A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>|
| Experimental: HZ/su-0,12 Group<br>Subjects will receive HZ/su vaccine on a 0,12-month schedule. | Biological: Herpes zoster vaccine GSK1437173A<br>* 2 doses administered intramuscularly (IM) in the deltoid region of the non-dominant arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Vaccine Response to Anti-glycoprotein E (Anti-gE) Antibodies as Determined by the Enzyme-linked Immunosorbent Assay (ELISA). | Vaccine response was defined as: for initially seronegative subjects, antibody concentration at post-vaccination ≥ 4 fold the cut-off for Anti-gE (4x97 mIU/mL); for initially seropositive subjects, antibody concentration at post-vaccination ≥ 4 fold the pre-vaccination antibody concentration. The objective required a comparison of VRR between 0,6-months and 0,12-months schedules. | At one month (M1) after Dose 2 | 
| Concentrations of Antibodies Against Anti-gE as Determined by ELISA. |  | At one month (M1) after Dose 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Antibodies Against Anti-gE as Determined by ELISA. |  | Prior (PRE) to vaccination and twelve (M12) post Dose 2 | 
| Number of Subjects With Solicited Local Symptoms. | Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/spontaneously painful. Grade 3 swelling/redness was defined as swelling/redness larger than (>) 100 millimeters (mm). Any is defined as incidence of the specified symptom regardless of intensity. | During the 7 day period (Days 0-6) following each dose (D) | 
| Number of Subjects With Solicited General Symptoms. | Assessed solicited general symptoms were Fatigue, Gastrointestinal (meaning nausea, vomiting, diarrhoea and/or abdominal pain), Headache, Myalgia, Shivering and Temperature (temperature higher than [≥] 37.5 degrees Celsius [°C]). Any = occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Fatigue = fatigue that prevented normal activity. Grade 3 Gastrointestinal = gastrointestinal that prevented normal every day activities. Grade 3 Headache = headache that prevented normal activity. Grade 3 Myalgia = myalgia that prevented normal activity. Grade 3 Shivering = shivering that prevented normal activity. Grade 3 Temperature = temperature higher than (>) 39.0°C. | During the 7 day period (Days 0-6) following each dose (D) | 
| Number of Subjects With Unsolicited Adverse Events (AEs). | An adverse event (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. | During the 30 Days (Day 0-29) following vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs). | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity. | From first vaccination up to one month (30 Days) post last vaccination | 
| Number of Subjects With SAE(s). | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity. | Starting from 30 Days post last vaccine administration up to study end at Month 24 | 
| Number of Days With Solicited Local Symptoms. | Each dose was abbreviated as follows: D1 = Dose 1, D2 = Dose 2. | During the 7 Days (Day 0-6) following vaccination | 
| Number of Days With Solicited General Symptoms. | Each dose was abbreviated as follows: D1 = Dose 1, D2 = Dose 2. | During the 7 Days (Day 0-6) following vaccination | 
| Number of Subjects With 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 Dose 1 up to one month (30 days) following the last vaccine dose administration (Dose 2) | 
| Number of Subjects With 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 one month (30 Days) following the last vaccine administration up to study end at Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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≥ 50 years of age, Herpes zoster, Safety, Immunogenicity, Adults