Immunogenicity and Safety Study of GSK Biologicals' Herpes Zoster Vaccine With Various Formulations in Adults >= 50 Years

Study Overview
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Brief Summary
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The goal of this randomized observer-blind trial is to further refine the formulation of vaccines containing GSK1437173A in older adults by comparing the cellular and humoral immune responses and the safety profiles of the different formulations.

Official Title
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Immunogenicity and Safety Study of Different Formulations of GSK Biologicals' Herpes Zoster Vaccine 1437173A When Administered Twice in Adults Aged 50 Years and 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: A male or female 50 years of age or above at the time of the first vaccination; Written informed consent obtained from the subject; Subjects who the investigator believes that they can and will comply with the requirements of the protocol should be enrolled in the study; 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 or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period; Chronic administration (defined as more than 14 consecutive days) of immunosuppressants or other immune-modifying drugs within three months prior to the first vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within one month before the first study vaccination or scheduled within 30 days after study vaccination; Previous vaccination against HZ; Previous vaccination against varicella; History of HZ; History of allergic disease or reactions likely to be exacerbated by any component of the vaccine; Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease or immunosuppressive/cytotoxic therapy; Administration of immunoglobulins and/or any blood products within the 3 months preceding the first injection of study vaccine or planned administration during the study period; Acute disease at the time of enrolment. Any other condition that, in the opinion of the investigator, might interfere with the evaluations required by the study; History of or current drug and/or alcohol abuse; Pregnant or lactating female; Female planning to become pregnant or planning to discontinue contraceptive precautions if of childbearing potential.

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 formulation 1 Group<br>Male or female subjects, 50 years of age or above, who received 2 doses of GSK1437173A (gE/ASO1B and gE/ASO1E) formulation 1 vaccine, administered intramuscularly in the upper deltoid region of the non-dominant arm on a 0, 2 month schedule. | Biological: Herpes zoster vaccine GSK1437173A<br>* 2 vaccinations at Months 0 and 2 with GSK1437173A (different formulations)<br>* Other names: gE/AS01B;|
| Experimental: GSK1437173A formulation 2 Group<br>Male or female subjects, 50 years of age or above, who received 2 doses of GSK1437173A (gE/ASO1B and gE/ASO1E) GSK1437173A formulation 2 vaccine, administered intramuscularly in the upper deltoid region of the non-dominant arm on a 0, 2 month schedule. | Biological: Herpes zoster vaccine GSK1437173A<br>* 2 vaccinations at Months 0 and 2 with GSK1437173A (different formulations)<br>* Other names: gE/AS01B;|
| Experimental: GSK1437173A formulation 3 Group<br>Male or female subjects, 50 years of age or above, who received 2 doses of GSK1437173A (gE/ASO1B and gE/ASO1E) formulation 3 vaccine, administered intramuscularly in the upper deltoid region of the non-dominant arm on a 0, 2 month schedule. | Biological: Herpes zoster vaccine GSK1437173A<br>* 2 vaccinations at Months 0 and 2 with GSK1437173A (different formulations)<br>* Other names: gE/AS01B;|
| Placebo Comparator: Control Group<br>Male or female subjects, 50 years of age or above, who received 2 doses of saline solution (placebo), administered intramuscularly in the upper deltoid region of the non-dominant arm on a 0, 2 month schedule. | Biological: Placebo<br>* 2 vaccinations at Months 0 and 2 with placebo<br>* Other names: Placebo/Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of gE-specific Cluster of Differentiation 4 (CD4+) T-cells Expressing at Least 2 Different Immunological Activation Markers | The analysis focused on CD4+ T-cells expressing at least 2 immunological activation markers among Interferon gamma (IFN-γ), Interleukin 2 (IL-2), Tumour Necrosis Factor alpha (TNF-α) and CD40 Ligand (CD40L). Frequencies were determined by in vitro Intracellular Cytokine Staining (ICS). | One month after the second vaccination (Month 3) | 
| Frequency of Varicella-Zoster Virus (VZV)-Specific CD4+ T-cells Expressing at Least 2 Different Immunological Activation Markers | The analysis focused on CD4+ T-cells expressing at least 2 immunological activation markers among Interferon gamma (IFN-γ), Interleukin 2 (IL-2), Tumour Necrosis Factor alpha (TNF-α) and CD40 Ligand (CD40L). Frequencies were determined by in vitro Intracellular Cytokine Staining (ICS). | One month after the second vaccination (Month 3) | 
| Anti-glycoprotein E (gE) 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). | One month after the second vaccination (Month 3) | 
| Anti-VZV 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). | One month after the second vaccination (Month 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequencies of gE-specific CD4+ T-cells Expressing at Least 2 Different Immunological Activation Markers | The analysis focused on CD4+ T-cells expressing at least 2 immunological activation markers among Interferon gamma (IFN-γ), Interleukin 2 (IL-2), Tumour Necrosis Factor alpha (TNF-α) and CD40 Ligand (CD40L). Frequencies were determined by in vitro Intracellular Cytokine Staining (ICS). | At Month 0 and at Month 2 | 
| Frequency of VZV-specific CD4+ T-cells Expressing at Least 2 Different Immunological Activation Markers | The analysis focused on CD4+ T-cells expressing at least 2 immunological activation markers among Interferon gamma (IFN-γ), Interleukin 2 (IL-2), Tumour Necrosis Factor alpha (TNF-α) and CD40 Ligand (CD40L). Frequencies were determined by in vitro Intracellular Cytokine Staining (ICS). | At Month 0 and at Month 2 | 
| Anti-gE 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 0 and at Month 2 | 
| Anti-VZV 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 0 and at Month 2 | 
| 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 after 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 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 higher than (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination. | During the 7-day (Days 0-6)post-vaccination period after 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. | Within 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. | From Month 0 up to Month 8 | 
| 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 period after Month 8 up to the end of the study at Month 14 | 
| Number of Subjects With Any New Onset of Autoimmune Diseases (NOADs) | Any new onset of autoimmune diseases 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. | From Month 0 until Month 8 | 
| Number of Subjects With Any New Onset of Autoimmune Diseases (NOADs) | Any new onset of autoimmune diseases 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 period after Month 8 up to the end of the study at Month 14 | 
| Number of Subjects With Suspected Cases of Herpes Zoster (HZ) | A suspected case of HZ was defined as a rash consistent with HZ. | From Month 0 until Month 8 | 
| Number of Subjects With Suspected Cases of Herpes Zoster (HZ) | A suspected case of HZ is defined as a rash consistent with HZ. | During the period after Month 8 up to the end of the study at Month 14 | 
| Number of Subjects With Haematological and Biochemical Parameters Unknown, Below, Within or Above the Normal Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hematocrit (HCT), Hemoglobin (HGB), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Mean Corpuscular Volume (MCV), Monocytes (MON), Neutrophils (NEU), Partial Thromboplastin Time (PTT), Platelets (PLAT), Prothrombin Time (PT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 0 | 
| Number of Subjects With Haematological and Biochemical Parameters Unknown, Below, Within or Above the Normal Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hematocrit (HCT), Hemoglobin (HGB), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Mean Corpuscular Volume (MCV), Monocytes (MON), Neutrophils (NEU), Partial Thromboplastin Time (PTT), Platelets (PLAT), Prothrombin Time (PT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 2 | 
| Number of Subjects With Haematological and Biochemical Parameters Unknown, Below, Within or Above the Normal Ranges | Hematological and biochemical parameters assessed were Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Basophils (BAS), Calcium (CAL), Creatinine (CREA), Eosinophils (EOS), Fibrinogen (FIBR), Hematocrit (HCT), Hemoglobin (HGB), Lactate Dehydrogenase (LDH), Lymphocytes (LYM), Mean Corpuscular Volume (MCV), Monocytes (MON), Neutrophils (NEU), Partial Thromboplastin Time (PTT), Platelets (PLAT), Prothrombin Time (PT), Red Blood Cells (RBC), Total Protein (TP) and White Blood Cells (WBC). | At Month 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytokine, Vaccine, Herpes Zoster (HZ), Cell mediated immunity (CMI), Antibody response, Varicella Zoster Virus (VZV), Shingles