Study to Evaluate Efficacy, Safety, and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Herpes Zoster Vaccine GSK1437173A

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of GSK Biologicals' vaccine GSK1437173A in the prevention of Herpes zoster (HZ) in autologous haematopoietic cell transplant recipients 18 years of age and older. To this end, the study will evaluate vaccine efficacy (VE) of the GSK1437173A vaccine, administered on a 2-dose schedule, compared to placebo in reducing the risk of developing HZ in this population.

Official Title
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Observer-blind Study to Evaluate Efficacy, Safety, and Immunogenicity of GSK Biologicals' Herpes Zoster Vaccine GSK1437173A

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: Study entry (enrollment) occurs at the Pre-vaccination visit. Subjects who the investigator believes can and will comply with the requirements of the protocol. Written informed consent obtained from the subject. A male or female aged 18 years or older at the time of study entry. Has undergone or will undergo autologous HCT within 50-70 days prior to the first vaccination with the study vaccine/placebo, and there are no plans for additional HCTs. 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 with the study vaccine/placebo, 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 12 months after completion of the vaccination series (i.e., until Month 13). 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/placebo, or planned use during the study period. However, the investigational use of a registered or non-registered product to treat the subject's underlying disease for which the HCT was undertaken, or a complication of the underlying disease, is allowed. Previous vaccination against HZ or varicella within the 12 months preceding the first dose of study vaccine/placebo. Planned administration during the study of a HZ vaccine other than the study vaccine. Occurrence of a varicella or HZ episode by clinical history within the 12 months preceding the first dose of study vaccine/placebo. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine or study material and equipment. Prophylactic antiviral therapy with activity against Varicella Zoster Virus (VZV) expected to last more than 6 months after transplantation. Administration and/or planned administration of a vaccine not foreseen by the study protocol between HCT and 30 days after the last dose of study vaccine/placebo. However, licensed non-replicating vaccines may be administered up to 8 days prior to dose 1and/or 2, and/or at least 14 days after any dose of study vaccine/placebo. HIV infection by clinical history. Pregnant or lactating female. Female planning to become pregnant or planning to discontinue contraceptive precautions (if of childbearing potential) before Month 13 (i.e., one year after the last dose of study vaccine/placebo).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 received 2 doses of the candidate HZ vaccine GSK 1437173A, administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 1 Month schedule. | Biological: Herpes Zoster vaccine GSK1437173A<br>* 2 doses administered intramuscularly (IM) in deltoid region of non-dominant arm<br>|
| Placebo Comparator: Placebo Group<br>Subjects received 2 doses of placebo (saline solution), administered intramuscularly (IM) in deltoid region of non-dominant arm, according to a 0, 1 Month schedule. | Biological: Placebo<br>* 2 doses administered IM in deltoid region of 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 Confirmed Herpes Zoster (HZ) Episode | A suspected case of HZ was defined as (1) a new rash characteristic of HZ (e.g., unilateral, dermatomal and accompanied by pain broadly defined to include allodynia, pruritus or other sensations), or a vesicular rash suggestive of VZV infection regardless of the distribution, and no alternative diagnosis; or (2) a clinical presentation (symptoms and/or signs) and specific laboratory findings* suggestive of VZV infection in the absence of characteristic HZ or VZV rash. A suspected case of HZ was confirmed either: by Polymerase Chain Reaction (PCR) or by the HZ Ascertainment Committee (HZAC), consisting of physicians with HZ expertise. | From Month 0 until the cut-off date for final analysis (median follow-up was of 21 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of 'Worst' HZ-associated Pain | Duration of HZ-associated pain rated as 3 or greater on the 'worst pain' Zoster Brief Pain Inventory (ZBPI) question, following the onset of a confirmed HZ rash over the entire pain reporting period in subjects with confirmed HZ; presented as T (day) [=the sum of follow-up period (for subjects without severe worst pain T is 1, for subjects with severe worst pain T is the duration of severe worst pain) expressed in days]. | From Month 0 until study end (4 years approximately), from the onset of a confirmed HZ rash over the entire pain reporting period | 
| Number of Subjects With Confirmed HZ-associated Complications | This analysis excluded complications that were linked to a confirmed HZ case that occurred after the start of the relapse treatment. | From Month 0 until the cut-off date for final analysis (median follow-up was of 21 months) | 
| Number of Subjects With Postherpetic Neuralgia (PHN) | This analysis excluded PHN episodes that were linked to a confirmed HZ case that occurred after the start of the relapse treatment. | From Month 0 until study end (21 months median follow-up) | 
| Antigen-glycoprotein E (gE) Antibody Concentrations in a Sub-cohort of Subjects | Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in milli-international units per milliliter (mIU/mL). The seropositivity cut-off value was greater than or equal to (≥) 97 mIU/mL. | At Months 0, 1, 2, 13 and 25 | 
| 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 = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 100 millimeters (mm) of injection site. | During 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, headache, myalgia, shivering and fever [defined as axillary/tympanic temperature equal to or above 37.5 degrees Celsius (°C) or rectal temperature equal to or above 38.0 °C]. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. | During 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) | 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) post-vaccination period | 
| Number of Subjects With Any and Related 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 Month 0 up to 365 days post last vaccination | 
| Number of Subjects With Any Relapse | Relapse was defined as the occurrence of the underlying malignancy or disease for which the HCT was undertaken. | From Month 0 until study end (approximate median of 29 months follow-up - minimum 1 year and maximum 4 years) | 
| Number of Subjects With Any Serious Adverse Events (SAEs) and Related SAEs to GSK Study Vaccine/Placebo | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. This enpoint also presents SAES related to the GSK study vaccine/placebo. | From Month 0 until 365 days post last vaccination (approximate median of 29 months follow-up - minimum 1 year and maximum 4 years) | 
| Number of Subjects With Fatal SAEs and SAEs Related to Study Participation or to a GSK Concomitant Medication or Vaccination | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject. This endpoint presents fatal SAEs and SAEs related to study participation or to a concurrent GSK medication/vaccine. | From the Pre-vaccination visit (Up to 110 days prior Month 0) until study end (approximate median of 29 months follow-up minimum 1 year and maximum 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Observer-blind, Efficacy, Immunogenicity, Vaccination, Adult autologous haematopoietic cell transplant recipients, Herpes Zoster