Month 30 & 42 Extension Studies of CRD-004 Primary Study

Study Overview
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Brief Summary
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The safety and immunogenicity of the GSK324332A vaccine has been evaluated up to Month 12 post-vaccination in the primary study. In the extension studies presented here, the persistence of the cellular and humoral immune responses will be evaluated 30 and 42 months after the first vaccination in young and elderly adults who received the GSK324332A vaccine. This protocol posting deals only with objectives & outcome measures of the extension phase at Months 30 and 42. No new recruitment will be done in these extension phases of the primary study. No vaccines are administered in this phase of the study.

Detailed Description
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All subjects in these extension phases of the study were previously vaccinated with the investigational herpes zoster vaccine GSK1437173A. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007. Further details on the primary study can be found on our GSK study register (https://www.gsk-studyregister.com/advanced-search) by searching on the GSK study identifier 101501.

Official Title
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An Extension Study to Evaluate the Persistence of the Immune Responses Induced by GSK Biologicals Zoster Vaccine, GSK324332A, Administered in Healthy Adult Subjects Aged 18-30 Years and 50-70 Years

Conditions
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Herpes Zoster

Intervention / Treatment
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* Procedure: Blood sampling for assay of persistence of immunogenicity


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 should be enrolled in the study; Subjects who successfully completed the primary study and who did not receive Varilrix in the primary study; Written informed consent obtained from the subject; Free of obvious health problems as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) within 1 month preceding the study start, or planned use during the study period; Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within three months prior to the first study procedure, including corticosteroids, except inhaled and topical steroids are allowed; Administration or planned administration of a vaccine not foreseen by the study protocol within 2 weeks before the first study procedure, with the exception of the Influenza vaccine, which can be administered 1 week preceding the first study procedure; Previous vaccination against HZ, except the study vaccine administered in the primary study; History of HZ (shingles); Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination; Administration of immunoglobulins and/or any blood products within the 3 months preceding the first study procedure or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK1437173A 18-30 Years Old Group<br>Subjects aged 18 to 30 years old receiving 2 doses GSK1437173A vaccine in the primary study. | Procedure: Blood sampling for assay of persistence of immunogenicity<br>* Two blood samples: 30 and 42 months after first vaccination<br>|
| Experimental: GSK1437173A 50-70 Years Old Group<br>Subjects aged 50 to 70 years old receiving 2 doses GSK1437173A vaccine in the primary study. | Procedure: Blood sampling for assay of persistence of immunogenicity<br>* Two blood samples: 30 and 42 months after first vaccination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequencies of Glycoprotein E (gE)-Specific Cluster of Differentiation 4 (CD4) / CD8 T Cells With at Least Two Antigen-specific Cytokines: Interferon Gamma (IFN-γ), Interleukin 2 (IL-2), Tumor Necrosis Factor Alpha (TNF-α), CD 40 Ligand (CD40L). | The analysis focused on those gE-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, and CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE was performed, since no long-term vaccine effect on gE-specific CD8 T cell response was detected. | At Month 30 after the first vaccination. | 
| Frequencies of Varicella Zoster Virus (VZV)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L). | The analysis focused on those VZV-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to VZV was performed, since no long-term vaccine effect on VZV-specific CD8 T cell response was detected. | At Month 30 after the first vaccination | 
| Frequencies of Glycoprotein E (gE)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L). | The analysis focused on those gE-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE was performed, since no long-term vaccine effect on gE-specific CD8 T cell response was detected. | At Month 42 after the first vaccination | 
| Frequencies of Varicella Zoster Virus (VZV)-Specific CD4 / CD8 T Cells With at Least Two Antigen-specific Cytokines (IFN-γ, IL-2, TNF-α, CD40L). | The analysis focused on those VZV-specific CD4 T cells secreting at least two different cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to VZV was performed, since no long-term vaccine effect on VZV-specific CD8 T cell response was detected. | At Month 42 after the first vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequencies of gE- and VZV-specific CD4/CD8 T Cells With Antigen-specific IFN-γ and/or IL-2 and/or TNF-α and/or CD40L Secretion/Expression. | The analysis focused on those gE- and VZV-specific CD4 T cells secreting any cytokines among IFN-γ, IL-2, TNF-α, CD40L as determined by intracellular cytokine staining (ICS). No analysis of the immunogenicity data on CD8 T cell response to gE or VZV was performed, since no long-term vaccine effect on gE- and VZV-specific CD8 T cell response was detected. | At Months 30 and 42 after the first vaccination | 
| Anti-gE Antibody (Ab) Concentrations | As determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and expressed as ELISA units per milliliter (EL.U/mL). | At months 30 and 42 after the first vaccination | 
| Anti-VZV Ab Concentrations | As determined by the Enzyme-Linked Immunosorbent Assay (ELISA) and expressed as ELISA units per milliliter (EL.U/mL). | At months 30 and 42 after the first vaccination | 
| Frequencies of gE-specific Memory B Cells | As determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay. | At months 30 and 42 after the first vaccination | 
| Frequencies of VZV-specific Memory B Cells | As determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay. | At months 30 and 42 after the first vaccination | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of existing hospitalization, result in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. | From Month 30 to study end Month 42 after the first vaccination | 
| Number of Subjects With Clinically Diagnosed Herpes Zoster (HZ) Episodes | This assay tabulated the number of subjects with clinically diagnosed HZ episodes, defined as any cutaneous HZ-like rash. | From last primary study visit (Month 12) to study end at Month 42 after the first vaccination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK Biologicals, Varicella Zoster Virus (VZV), Intracellular cytokine staining (ICS), Vaccine, Cell mediated immunity (CMI), Herpes Zoster (HZ), Shingles