Safety & Immunogenicity of GlaxoSmithKline Biologicals' Herpes Zoster Vaccine 1437173A

Study Overview
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Brief Summary
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The purpose of this observer-blind study is to evaluate the safety and immunogenicity of GlaxoSmithKline Biologicals' investigational Herpes Zoster vaccine GSK1437173A when administered as 2 doses or 3 doses to hematopoietic stem cell transplant (HCT) recipients.

Detailed Description
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The Protocol Posting has been updated following Protocol amendment 2, Sep 2009. The sections impacted are: eligibility criteria.

Official Title
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Safety and Immunogenicity of GlaxoSmithKline Biologicals' Herpes Zoster Vaccine 1437173A

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: Herpes Zoster Vaccine 1437173A
* Biological: Placebo vaccine (saline)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that they can and will comply with the requirements of the protocol; Male and female subjects at least 18 years old at the time of vaccination; Serological evidence of prior VZV infection for all subjects born in 1980 or later and for subjects born outside the US before 1980 in a tropical or sub-tropical region. No testing for serological evidence of prior VZV infection is required for US subjects born before 1980; Has undergone autologous HCT within the past 50-70 days for treatment of Hodgkin lymphoma, non-Hodgkin lymphoma (T or B cell), myeloma or acute myeloid leukemia, and there are no plans for additional HCTs Written informed consent obtained from the subject; If the subject is female, she must be of non-childbearing potential or if she is of childbearing potential, she must practice adequate contraception for 30 days prior to vaccination, have a negative pregnancy test and continue such precautions for 2 months after completion of the vaccination series. Exclusion Criteria: Use of any investigational non-registered product other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period; Administration or planned administration of a vaccine that is not part of the study protocol since transplantation. However licensed non-replicating vaccines (i.e. inactivated and subunit vaccines, including inactivated and subunit influenza vaccines, with or without adjuvant) may be administered up to 8 days prior to dose 1; Administration of immunoglobulins since transplantation; Previous vaccination against varicella or HZ; History of HZ within the previous 12 months; Known exposure to VZV since transplantation; Evidence of active infection at the time of enrollment including a temperature of ≥ 37.5° C or any serious HCT-related complication; History of allergic disease or reactions likely to be exacerbated by any component of the vaccine; Hypersensitivity or intolerance to acyclovir or valacyclovir; Pregnant or lactating female.

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: GSK 1437173A F1 Group<br>Male or female subjects, 18 years of age or older at the time of the first vaccination, received 3 doses of GSK 1437173A formulation 1 (F1) vaccine, administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule. | Biological: Herpes Zoster Vaccine 1437173A<br>* Different formulations of investigational vaccine (GSK 1437173A) administered in 2 or 3 doses intramuscularly.<br>|
| Experimental: GSK 1437173A F2 Group<br>Male or female subjects, 18 years of age or older at the time of the first vaccination, received 3 doses of GSK 1437173A formulation 2 (F2) vaccine, administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule. | Biological: Herpes Zoster Vaccine 1437173A<br>* Different formulations of investigational vaccine (GSK 1437173A) administered in 2 or 3 doses intramuscularly.<br>|
| Experimental: Placebo-GSK 1437173A F1 Group<br>Male or female subjects, 18 years of age or older at the time of the first vaccination, received 1 dose of the placebo followed by 2 doses of GSK 1437173A F1 vaccine. For some safety analyses, this Group was split into Placebo 1D Group (results following placebo administration) and GSK 1437173A 2D Group (results following HZV administration). All vaccines were administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule. | Biological: Herpes Zoster Vaccine 1437173A<br>* Different formulations of investigational vaccine (GSK 1437173A) administered in 2 or 3 doses intramuscularly.<br>Biological: Placebo vaccine (saline)<br>* 1 or 3 doses of Placebo (saline) injected intramuscularly.<br>|
| Placebo Comparator: Placebo Group<br>Male or female subjects, 18 years of age or older at the time of the first vaccination, received 3 doses of placebo, administered intramuscularly in the upper deltoid region of non-dominant arm according to a 0,1,3-months schedule. | Biological: Placebo vaccine (saline)<br>* 1 or 3 doses of Placebo (saline) injected intramuscularly.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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-days (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, diarrhoea and abdominal pain], temperature [defined as oral temperature equal to or above (≥) 37.5 degrees Celsius (°C)], headache and myalgia. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 temperature = temperature higher than (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-days (Days 0-6) post-vaccination period following each dose and across doses | 
| Number of Subjects With Any and Grade 3 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. | During the 30-day (Days 0-29) post-vaccination period | 
| Number of Subjects With 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. | Any time during the study up to Day 29 after the last vaccination | 
| Number of Subjects With 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 (from Day 0 up to Month 15) | 
| Number of Subjects With Any New Onset of Autoimmune Diseases (NOADs) and Other Immune Mediated Inflammatory Disorders | Any new onset of autoimmune diseases and immune mediated inflammatory disorders were to be reported throughout the entire study period, whether or not they were considered to be possibly related to the treatment administration. These included neurological/demyelinating events, rheumatic and connective diseases, autoimmune endocrine diseases, inflammatory bowel diseases, autoimmune blood disorders, inflammatory skin disorders, other autoimmune/inflammatory events, autoimmune bullous skin diseases, vasculitis and liver autoimmune diseases. | Within the 30-day (Days 0-29) post last vaccination period | 
| Number of Subjects With Any New Onset of Autoimmune Diseases (NOADs) and Other Immune Mediated Inflammatory Disorders | Any new onset of autoimmune diseases and immune mediated inflammatory disorders were to be reported throughout the entire study period, whether or not they were considered to be possibly related to the treatment administration. These included neurological/demyelinating events, rheumatic and connective diseases, autoimmune endocrine diseases, inflammatory bowel diseases, autoimmune blood disorders, inflammatory skin disorders, other autoimmune/inflammatory events, autoimmune bullous skin diseases, vasculitis and liver autoimmune diseases. | During the entire study period (from Day 0 to Month 15) | 
| Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 0 | 
| Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 1 | 
| Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 2 | 
| Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 3 | 
| Number of Subjects With Hematological and Biochemical Parameters With Respect to Normal Laboratory Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hemoglobin (HGB), Hematocrit (HCT), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Monocytes (MON), Neutrophils (NEU), Platelets (PLAT), Prothrombin Time (PT), Partial Thromboplastin Time (PTT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 4 | 
| Frequency of gE-specific Cluster of Differentiation 4 (CD4) T-cells Expressing at Least 2 Cytokines | The analysis focused on CD4 T-cells expressing at least 2 cytokines among Interferon gamma [IFN-γ], Interleukin 2 [IL-2], Tumour Necrosis Factor alpha [TNF-α] and/or CD40 Ligand [CD40L] as determined by in vitro intracellular cytokine staining (ICS). | At Month 4 | 
| Anti-glycoprotein E (Anti-gE) Geometric Mean Antibody Concentrations | Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL). | At Month 4 | 
| Anti-gE Mean Antibody Concentrations | Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and are presented as mean concentrations, expressed in milli-international units per milliliter (mIU/mL). | At Month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of CD4 T-cells Specific for Varicella Zoster Virus (VZV) Antigens | The analysis focused on CD4 T-cells expressing at least 2 cytokines among Interferon gamma [IFN-γ], Interleukin 2 [IL-2], Tumour Necrosis Factor alpha [TNF-α] and/or CD40 Ligand [CD40L] as determined by in vitro intracellular cytokine staining (ICS). | At Months 0, 1, 2, 3, 4 and 15 | 
| Frequency of gE-specific Cluster of Differentiation 4 (CD4) T-cells Expressing at Least 2 Cytokines | The analysis focused on CD4 T-cells expressing at least 2 cytokines among Interferon gamma [IFN-γ], Interleukin 2 [IL-2], Tumour Necrosis Factor alpha [TNF-α] and/or CD40 Ligand [CD40L] as determined by in vitro intracellular cytokine staining (ICS). | At Months 0, 1, 2, 3 and 15 | 
| Varicella Zoster Virus (VZV)-Specific Geometric Mean Antibody Concentrations | Concentrations are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL). | At Months 0, 1, 2, 3, 4 and 15 | 
| VZV-specific Mean Antibody Concentrations | Concentrations are presented as mean concentrations, expressed in milli-international units per milliliter (mIU/mL). | At Months 0, 1, 2, 3, 4 and 15 | 
| Anti-gE Geometric Mean Antibody Concentrations | Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and are presented as geometric mean concentrations (GMCs), expressed in milli-international units per milliliter (mIU/mL). | At Months 0, 1, 2, 3 and 15 | 
| Anti-gE Mean Antibody Concentrations | Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and are presented as mean concentrations, expressed in milli-international units per milliliter (mIU/mL). | At Months 0, 1, 2, 3 and 15 | 
| Number of Subjects With Confirmed Herpes Zoster (HZ) Cases | A suspected case of HZ could be confirmed by PCR and/or by clinical review of the GSK physician responsible for the study. Rash lesion samples collected from subjects clinically diagnosed as having a suspected case of HZ were tested by by polymerase chain reaction (PCR) using standardized and validated procedures for the laboratory diagnosis of HZ. If the PCR specimen was inadequate or was missing, suspected HZ cases were to be classified as 'a confirmed case of HZ' or 'not a case of HZ' based on the determination by the GSK responsible physician of the study. | During the entire study period (from Day 0 to Month 15) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Safety, Herpes Zoster, Immunogenicity, Stem cell transplantation