Study to Evaluate Efficacy, Safety and Immunogenicity of GSK Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults Aged 50 Years and Older

Study Overview
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Brief Summary
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The purpose of this observer-blind study is to evaluate the efficacy, safety and immunogenicity of GSK Biologicals' candidate Herpes Zoster (HZ) vaccine in adults aged ≥ 50 years. Two studies [ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229)] are being conducted concurrently to evaluate efficacy of GSK1437173A vaccine. A pooled analysis of data from both studies combined will be conducted contingent on each study achieving its objectives. The protocol posting of study ZOSTER-022 also deals with the outcome measures related to the pooled analysis.

Detailed Description
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This protocol summary has been updated following Protocol Amendment 4 changes to study objectives and endpoints and the analyses of the objectives in 2 steps. Step 1 will include analyses of the following objectives of ZOSTER-006 (NCT01165177): all HZ VE objectives and all reactogenicity/safety and immunogenicity objectives. At step 2, all objectives of study ZOSTER-006 (NCT01165177) will be analyzed. Objectives already analyzed at step 1 will be re-analyzed (confirmatory descriptive in case of inferential analysis at step 1 or descriptive analysis otherwise). At step 2, pooled analyses of studies ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) are planned; overall PHN VE in subjects ≥ 70 YOA, and other pre-specified endpoints will be analyzed.

Official Title
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Efficacy, Safety, and Immunogenicity Study 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
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes will comply with the requirements of the protocol; Written informed consent obtained from the subject; A male or female aged 50 years or older at the time of the first vaccination; Female subjects of non-childbearing potential may be enrolled in the study; For this study population, non-childbearing potential is defined as current tubal ligation, hysterectomy, ovariectomy or post-menopause. OR 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 urine 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; 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; Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy; History of HZ; Previous vaccination against varicella or HZ; History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Additionally, consider allergic reactions to other material or equipment related to study participation; Significant underlying illness that in the opinion of the investigator would be expected to prevent completion of the study; Receipt of immunoglobulins and/or any blood products within the 90 days preceding the first dose of study vaccine or planned administration during the study period; Administration or planned administration of any other immunizations within 30 days before the first or second study vaccination or scheduled within 30 days after study vaccination. However, licensed non-replicating vaccines may be administered up to 8 days prior to each dose and/or at least 14 days after any dose of study vaccine; Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study; Acute disease and/or fever at the time of enrollment; Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Pregnant or lactating female; Female planning to become pregnant or planning to discontinue contraceptive precautions.

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: GSK1437173A group<br>Subjects will receive Herpes Zoster Vaccine GSK1437173A according to a 0, 2-month schedule | Biological: Herpes Zoster Vaccine GSK1437173A<br>* Intramuscular injection<br>|
| Placebo Comparator: Placebo group<br>Subjects will receive NaCl solution placebo according to a 0, 2-month schedule | Biological: Placebo<br>* Intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Confirmed Herpes Zoster (HZ) Cases | Confirmed HZ cases during the study were assessed in the Modified Total Vaccinated Cohort (mTVc) | During the entire study period (3 to 5 year period following Day 0) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any Episodes of Post-Herpetic Neuralgia (PHN) | The incidence of PHN was calculated using the modified total vaccinated chort. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With a Reduction of Duration of Severe 'Worst' HZ-associated Pain | Severe 'worst' pain was defined as HZ-associated pain rated as 3 or above on the 'worst pain' Zoster Brief Pain Inventory (ZBPI) questionnaire. The outcome assessed the duration of severe 'worst' HZ-associated pain following the onset of a confirmed HZ rash over the entire pain reporting period as measured by the ZBPI in subjects with confirmed HZ. This analysis involved any subject reporting clinically significant pain (i.e. pain with a score of 3 or more on a 0-10 point scale) at any time during the study. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Confirmed HZ Episode Related Mortality | The analysis focused on the number of subjects who died due to HZ | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With HZ Related Complications | The analysis focused on the incidence of HZ complications in subjects with confirmed HZ | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Confirmed HZ Episode Related Hospitalizations | The analysis focused on confirmed HZ episode related hospitalizations. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With a Confirmed HZ Episode Having a Reduction of Duration of Pain Medication Associated With HZ | The analysis focused on patients who experienced a reduction in duration of pain medication administered for HZ in subjects with confirmed HZ. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With a Confirmed HZ Episode Taking Pain Medication Associated With HZ | The analysis focused on subjects taking pain medication due to HZ | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Days With Severe 'Worst' HZ-associated Pain. | Severe 'worst' pain was defined as HZ-associated pain rated as 3 or above on the 'worst pain' ZBPI questionnaire. This Outcome Measure was only assessed participants with confirmed HZ. This analysis involved any subject reporting ZBPI clinically significant pain (i.e. pain with a score of 3 or more on a 0-10 point scale) at any time during the study. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Confirmed HZ Episode Related Mortality and Hospitalizations | The analysis focused on confirmed HZ episode related hospitalizations and deaths. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With HZ Related Complications, by Complication Type | Complication types included HZ vasculitis, Disseminated Disease, Ophtalmic Disease, Neurologic Disease, Visceral Disease and Stroke. This Outcome Measure was only assessed participants with confirmed HZ. | During the entire study period (3 to 5 year period following Day 0) | 
| Distribution of Pain Medication Associated With HZ | The distribution of pain medication included 1 to 3 or more separate medications. This Outcome Measure was only assessed on participants with confirmed HZ. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Days of Pain Medication Associated With HZ | The analysis was performed on subjects with a confirmed HZ episode | During the entire study period (3 to 5 year period following Day 0) | 
| 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 activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. Relationship analysis was not performed. | During the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, GI (gastrointestinal) symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), fever [defined as oral, axillary, rectal or tympanic temperature equal to or above 37.5 degrees Celsius (°C)], headache, myalgia, shivering and sweating. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = temperature> 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | Within the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Any and Grade 3 Symptoms (Solicited and Unsolicited) | Number of subjects with any and grade 3 solicited and unsolicited symptoms were tabulated | Within the 7-day (Days 0-6) post-vaccination period | 
| Number of Subjects With Any and Related Potential Immune Mediated Diseases (pIMDs) | Occurrence and relationship to vaccination of any potential immune-mediated diseases (pIMDs) in all subjects | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With AEs With Any and Related Medically Attended Visit | Occurrence and relationship to vaccination of medically attended visits (defined as hospitalizations, emergency room visits or visits to or from medical personnel), other than routine health care visits in all subjects. | From Month 0 to Month 8 post-vaccination | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | Occurrence, intensity and relationship to vaccination of unsolicited 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 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. | Within 30 days (Days 0 - 29) after each vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | Occurrence and relationship to vaccination of all SAEs in all subjects. 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. | Within the 30-day (Days 0-29) post-vaccination period, up to Month 14 and up to study end (3 to 5 year period following Day 0) | 
| Number of Subjects With SAEs Related to Study Participation or to a Concurrent GSK Medication/Vaccine | The number of subjects with SAEs related to study participation or to a concurrent GSK medication/vaccine were tabulated | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Fatal SAEs | Number of subjects with fatal SAEs during the entire study period were tabulated | During the entire study period (3 to 5 years following day 0) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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subjects 50 years and older, vaccine, immunogenicity, efficacy, Herpes Zoster, safety