Study to Evaluate Efficacy, Safety and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster (HZ) Vaccine GSK1437173A in Adults Aged 70 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 ≥ 70 years. Two studies (Zoster-006 [NCT01165177] and Zoster-022 [NCT01165229]) will be 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. This protocol posting 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. Pooled analyses of ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) will only be conducted if the primary objective herpes zoster vaccine efficacy (HZ VE) is demonstrated in both ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229) separately.

Official Title
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Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A in Adults Aged 70 Years or Older

Conditions
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Herpes Zoster, Herpes Zoster Vaccine

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 70 years or older at the time of the first vaccination. 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 enrolment. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose.

Ages Eligible for Study
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Minimum Age: 70 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: Zoster vaccine 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 Any Episodes of Herpes Zoster (HZ) | Confirmed HZ cases during the study in the modified total vaccinated cohort (mTVc). | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies ZOSTER-006 (NCT01165177) and ZOSTER-022 (NCT01165229): Number of Subjects With Post-herpetic Neuralgia (PHN) | Incidence of PHN calculated using the mTVc during the entire study period in subjects ≥ 70 years of age (YOA). | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Confirmed HZ | Occurrence of confirmed HZ during the entire study period in subjects ≥ 70 YOA. | 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 Post-herpetic Neuralgia (PHN) | PHN cases in the mTVc. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Days With Severe 'Worst' HZ-associated Pain | 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 Zoster Brief Pain Inventory (ZBPI) 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 Mortality and Hospitalizations | The number of subjects with confirmed HZ related mortality and hospitalizations were tabulated. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Overall Mortality and HZ-related Mortality | The number of subjects with overall mortality and HZ related mortality were tabulated. Evaluation of VE in the reduction of overall and HZ related mortality as per study objective was not performed due to low number of events reported. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Confirmed HZ Episode Related Hospitalizations | Incidence of overall and HZ-related hospitalizations during the study. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With HZ Related Complications | Incidence of HZ complications during the study in subjects with confirmed HZ. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects Receiving Pain Medication Associated With HZ | Incidence of use of pain medications throughout the study | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Days With Pain Medication Associated With HZ | Incidence of reduction of duration of pain medication associated with HZ throughout the study. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Occurrence, intensity of each solicited local symptom within 7 days (Days 0-6) after each vaccination, in subjects included in the 7-day diary card subset; 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 everyday normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms (including 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 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. | Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Unsolicited Adverse Events (AEs) | Occurrence, intensity and relationship to vaccination of unsolicited AEs during 30 days (Days 0-29) after each vaccination, 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 the 30 days (Days 0-29) after each vaccination | 
| Number of Subjects With Any and Related 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 Month 0 to Month 14 | 
| Number of Subjects With Fatal 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. | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With SAEs Related to Study Participation or Concomitant GSK Medication | The number of subjects with SAEs related to study participation or concomitant GSK medication were tabulated | During the entire study period (3 to 5 year period following day 0) | 
| Number of Subjects With Any and Related Potential Immune Mediated Diseases (pIMDs) | Occurrence and relationship to vaccination of any potential immune-mediated diseases (pIMDs) during the entire study period in all subjects | During the entire study period (3 to 5 year period following Day 0) | 
| Number of Subjects With Any and Related Medically Attended Visits | Occurrence and relationship to vaccination of medically attended visits other than routine health care visits, from Month 0 to Month 8 in all subjects. Medically attended visits were defined as events for which the subject received medical attention defined as hospitalization, an emergency room visit, or a visit to or from medical personnel (medical doctor) for any reason. Any medically attended visits= Occurrence of any medically attended visits regardless of intensity grade or relation to vaccination. | From Month 0 to Month 8 post-vaccination | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Overall Number of Subjects With PHN in Subjects ≥ 50 YOA | Incidence of PHN calculated using the mTVc during the entire study period in subjects ≥ 50 YOA. | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With a Reduction of PHN Incidence in Subjects ≥ 50 YOA With Confirmed HZ | Occurrence of PHN during the entire study period in all subjects with confirmed HZ. | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With at Least One Day of Severe 'Worst' HZ-associated Pain in Subjects ≥ 70 YOA With Confirmed HZ. | The duration of severe 'worst' HZ-associated pain following the onset of a confirmed HZ rash over the entire pain reporting period was measured by the ZBPI in subjects ≥ 70 YOA with confirmed HZ . | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Duration of Severe 'Worst' HZ-associated Pain in Subjects ≥ 70 YOA With Confirmed HZ. | Duration of severe 'worst' HZ-associated pain following the onset of a confirmed HZ rash over the entire pain reporting period was measured by the ZBPI in subjects ≥ 70 YOA with confirmed HZ. | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Occurrence, intensity of each solicited local symptom within 7 days (Days 0-6) after each vaccination, in subjects ≥ 70 YOA. Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | Within the 7-day (Days 0-6) post-vaccination period following each dose and across doses | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were fatigue, gastrointestinal symptoms, 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 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 following each dose and across doses | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Any,Grade 3 and Related Unsolicited AEs in Subjects ≥ 70 YOA | Occurrence, intensity and relationship to vaccination of unsolicited AEs during 30 days (Days 0-29) after each vaccination, according to the MedDRA classification, in subjects ≥ 70 YOA.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 | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Any and Related SAEs | Occurrence and relationship to vaccination of all SAEs from Month 0 to Month 14 in subjects ≥ 70 YOA. Related SAEs also included any SAEs related to study participation or concurrent GSK medication/vaccine. | From Month 0 to Month 14 | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Fatal SAEs | Fatal SAEs during the entire study period in subjects ≥ 70 YOA. | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Any and Related pIMDs | Occurrence and relationship to vaccination of any pIMDs during the entire study period in subjects ≥ 70 YOA. | During the entire study period (3 to 5 year period following Day 0) | 
| Outcome Measure for the Pooled Analysis of Combined Data From Studies Zoster-006 (NCT01165177) and Zoster-022 (NCT01165229): Number of Subjects With Any and Related Medically Attended Visits | 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, from Month 0 to Month 8 in subjects ≥ 70 YOA. | From Month 0 to Month 8 post-vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Subjects 70 years and older, Efficacy, Herpes Zoster, Safety, Adults, Vaccine