Consistency, Immunogenicity and Safety Study of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults ≥ 50 Years of Age

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate lot-to-lot consistency in terms of immunogenicity, and evaluate safety of the Herpes Zoster subunit (HZ/su) vaccine. The study is designed as a randomized, double-blind study with three parallel groups.

Official Title
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Consistency, Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults 50 Years of Age or Older

Conditions
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Herpes Zoster, Herpes Zoster Vaccine

Intervention / Treatment
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* Biological: Herpes Zoster 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 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 2 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. A prednisone dose of < 20 mg/day 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 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 (E.g. inactivated and subunit vaccines) within 8 days prior to or within 14 days after either dose of study vaccine. Administration of long-acting immune-modifying drugs within six months prior to the first vaccine dose or expected administration at any time during the study period. 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 product. Previous vaccination against HZ or varicella. Planned administration during the study of an HZ or varicella vaccine other than the study vaccine. History of HZ. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy. 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 enrollment. Fever is defined as temperature ≥ 37.5°C (99.5°F) on oral, axillary or tympanic route, or ≥ 38.0°C (100.4°F) on rectal route. The preferred route for recording temperature in this study will be oral. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/or any blood products within 3 months preceding the first dose of study vaccine or planned administration during the study period. Pregnant or lactating females. Females planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 4. Any condition which, in the opinion of the investigator, prevents the subject from participating in 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 injection unsafe.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HZ/su Lot A<br>Subjects will receive Lot A of the HZ/su vaccine at 0 and 2 months. The HZ/su vaccine composed of unique randomized combinations of an adjuvant lot and one gE lot. | Biological: Herpes Zoster vaccine (GSK 1437173A)<br>* 2 doses administered intramuscularly in deltoid region of non-dominant arm.<br>* Other names: HZ/su vaccine;|
| Experimental: HZ/su Lot B<br>Subjects will receive Lot B of the HZ/su vaccine at 0 and 2 months. The HZ/su vaccine composed of unique randomized combinations of an adjuvant lot and one gE lot. | Biological: Herpes Zoster vaccine (GSK 1437173A)<br>* 2 doses administered intramuscularly in deltoid region of non-dominant arm.<br>* Other names: HZ/su vaccine;|
| Experimental: HZ/su Lot C<br>Subjects will receive Lot C of the HZ/su vaccine at 0 and 2 months. The HZ/su vaccine composed of unique randomized combinations of an adjuvant lot and one gE lot. | Biological: Herpes Zoster vaccine (GSK 1437173A)<br>* 2 doses administered intramuscularly in deltoid region of non-dominant arm.<br>* Other names: HZ/su vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Anti-gE Antibody Concentrations Equal to or Above the Cut-off Value | Anti-gE antibody concentrations, as determined by Enzyme-linked Immunosorbent Assay (ELISA). The cut-off value was ≥ 97 milli international units per milliliter (mIU/mL). | At Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-gE Humoral Immunogenicity | Anti-gE antibody concentrations, were determined by ELISA, expressed as Geometric Mean Concentrations (GMCs), in milli international units per milliliter (mIU/mL). | At Month 0 and Month 3 | 
| Number of Vaccine Responders for Anti-gE Concentrations as Determined by 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. | At Month 3 | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = significant pain at rest, that prevented normal every day activities. | Within 7 days (Days 0-6) after each vaccine dose and across doses | 
| Number of Days With Any Solicited Local Symptoms | The number of days with any local symptoms reported during the solicited post-vaccination period. | During the 7 days (Days 0-6) after each vaccine dose | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal (nausea, vomiting, diarrhea and/or abdominal pain), headache, myalgia, shivering and temperature [defined as oral temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature= temperature > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within 7 days (Days 0-6) after each vaccine dose and across doses | 
| Number of Days With Any Solicited General Symptoms | The number of days with any general symptoms reported during the solicited post-vaccination period. | During the 7 days (Days 0-6) after each vaccine dose | 
| Number of Subjects With Any Potential Immune-Mediated Diseases (pIMDs) | Potential immune-mediated diseases (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 up to 30 days post last vaccination (Month 0-Month 3) and from Month 4 until study end (Month 14) | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (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 30 days (Days 0-29) after each vaccination | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | From first vaccination up to 30 days post last vaccination (Month 0-Month 3) and from Month 4 to study end (Month 14) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Zoster, Immunogenicity, Adults, Consistency