Evaluation of the Long-term Persistence of GlaxoSmithKline (GSK) Biologicals' Candidate Cytomegalovirus (CMV) Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the persistence of the vaccine induced immune responses at Month 48 (Year 4) and Month 60 (Year 5) in healthy subjects who received 3 doses of GSK Biologicals' candidate CMV vaccine according to a 0-1-6 month schedule during the primary study 108890 (NCT00435396) (vaccine group). The immune response to CMV infection in naturally infected subjects who participated in the screening visit of the primary study 108890 (NCT00435396) and who were tested CMV-seropositive, will be used as a reference value (seropositive reference group). In addition, this study will continue to assess the occurrence of CMV infections as well as the continued development and validation of read-outs in the CMV project. The primary vaccination phase and Year 2 follow-up were posted as a separate protocol posting (NCT00435396).

Detailed Description
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During the long-term follow-up study, all subjects who received 3 doses of GSK Biologicals' candidate CMV vaccine according to a 0-1-6 month schedule during the primary study 108890 (NCT00435396) will be invited to participate at Visit 8 (Year 4) and Visit 9 (Year 5) as the vaccine group. In addition, the healthy subjects who participated in the screening visit of the primary study 108890 (NCT00435396) and who were tested CMV-seropositive will be invited to Visit 9 (Year 5) of this study as the seropositive reference group.This Protocol Posting has been updated following Protocol Amendment 1, March 2012, leading to the update of brief summary, intervention model, enrolment, outcome measures, eligibility and arms.

Official Title
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A Follow-up Study to Evaluate the Long-term Persistence of GSK Biologicals' Candidate CMV Vaccine Administered to Male Adults

Conditions
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Infections, Cytomegalovirus

Intervention / Treatment
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* Procedure: Blood sampling
* Biological: GSK149203A


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 (e.g., return for follow-up visits) should be enrolled in the study. Written informed consent obtained from the subject. Healthy subjects as established by clinical evaluation (medical history and physical examination) before entering in the study. Subjects of the vaccine group should in addition satisfy the following criterion: • Subjects who participated in the primary study 108890 (NCT00435396), having received 3 doses of the GSK's CMV candidate vaccine and having completed the Year 2 follow-up study 109211 (NCT00435396). Subjects of the seropositive reference group should in addition satisfy the following criterion: • Subjects who participated in the screening visit of the primary study 108890 (NCT00435396), and whose blood sample taken at this visit was tested CMV positive. Exclusion Criteria: Use, or planned use, of any investigational or non-registered product (drug or vaccine) during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to study visit(s). For corticosteroids, this will mean prednisone, 20mg/day, or equivalent. Inhaled and topical steroids are allowed. Administration of immunoglobulins and/or any blood products within three months preceding study visit(s). Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). For subjects in the vaccine group, the following exclusion criterion should be checked in addition: • Administration of any additional CMV vaccine since end of primary study 108890 (NCT00435396). For subjects in the seropositive reference group, the following exclusion criterion should be checked in addition: • Administration of any CMV vaccine since the screening visit of primary study 108890 (NCT00435396).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK149203A S- Group<br>Male subjects who received 3 doses of GSK Biologicals' candidate GSK149203A vaccine according to a 0-1-6 month schedule in the primary study 108890 (NCT00435396). | Procedure: Blood sampling<br>* Blood samples will be collected at 2 time points: At the long-term follow-up at approximately Month 48 of study (= ± 42 months post dose 3) from all subjects in the vaccine group. At the long-term follow-up at approximately Month 60 of study (= ± 54 months post dose 3) from all subjects.<br>Biological: GSK149203A<br>* GSK Biologicals' Recombinant CMV glycoprotein B Vaccine, Intramuscular injection, 3 doses<br>|
| Other: GSK149203A S+ Group<br>Male subjects who were assessed as being naturally infected with Cytomegalovirus (CMV) at the screening visit of the primary study 108890 (NCT00435396). | Procedure: Blood sampling<br>* Blood samples will be collected at 2 time points: At the long-term follow-up at approximately Month 48 of study (= ± 42 months post dose 3) from all subjects in the vaccine group. At the long-term follow-up at approximately Month 60 of study (= ± 54 months post dose 3) from all subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of Antibodies Against Anti-Glycoprotein B (gB) Immunoglobulin G (IgG) | Anti-gB IgG antibody concentrations were presented as Geometric Mean Concentrations (GMCs) and expressed in ELISA units per milliliter (EL.U/mL), as assessed by Enzyme-linked Immunosorbent Assay (ELISA). Data were collected at Month 48 (M48) and Month 60 (M60) from all subjects. | At Month 48 and Month 60 | 
| Number of Subjects With Neutralizing Response Against Anti-Cytomegalovirus (CMV) Antibodies | The neutralizing antibodies were to be measured using an in-house micro-neutralization assay. | At Month 48 and Month 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive Statistics on Avidity Index (%) of Anti-gB IgG Antibodies | Avidity for anti-gB IgG antibodies was assessed by the ELISA Avidity index method in all subjects, at Month 48 (M48) and Month 60 (M60). This assay has been developed according to Souza et al (Rev.Inst.med.Trop.S.Paulo 45;323-326; 2003) using an elution step with urea to remove low-avidity antibodies from CMV antigen. The avidity index was calculated as the mean absorbance of reactions in which the immune complexes are exposed to urea divided by the mean absorbance of reactions in which the immune complexes are not exposed to urea, expressed as a percentage. | At Month 48 and Month 60 | 
| Descriptive Statistics on the Frequency of gB-specific Cluster of Differentiation (CD4+/CD8+) T-cells Expressing at Least Two Immune Markers | Among the immune markers determined by the Intracellular cytokine staining (ICS) were Interferon-gamma (INF-γ), Interleukin-2 (IL-2), Tumor necrosis factor-alpha (TNF-α), and CD40-Ligand (CD40-L). Data were collected for all subjects at Month 48 (M48) and Month 60 (M60). | At Month 48 and Month 60 | 
| Desciptive Statistics on the Frequency of gB-specific Memory B-cells (by ELISPOT) | Memory B cells specific to the CMV gB antigen, as assessed by the Enzyme-linked Immunosorbent Spot (ELISPOT) method, were expressed as a frequency of the specific memory B-cells per million memory B-cells. Data were collected for all subjects at Month 48 (M48) and Month 60 (M60). | At Month 48 and Month 60 | 
| Number of Subjects With Response for Anti-CMV Tegument IgG Antibodies | CMV infection was determined by the anti-CMV proteins antibody response, using ELISA. Data were collected for all subjects at Month 48 (M48) and Month 60 (M60) in the Vaccine group (GSK149203A S- Group). All subjects from the Reference group (GSK149203A S+ Group) were positive for the anti-CMV tegument IgG antibodies at the screening visit. | At Month 48 and Month 60 | 
| Assessment of CMV Infection by CMV Specific Desoxyribonucleic Acid (DNA) in Viral Load | CMV DNA viral loads were assessed using quantitative Polymerase Chain Reaction (qPCR). Data were presented for subjects included in the Vaccine group (GSK149203A S- Group). | At Month 48 and Month 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytomegalovirus, Vaccine