Study to Evaluate Safety and Immunogenicity of the GSK Bio CMV Vaccine in CMV-seronegative Healthy Male Adult Subjects

Study Overview
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Brief Summary
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This will be the first time in humans (FTIH) study with the GSK Bio recombinant gB antigen to evaluate safety and immunogenicity of this CMV candidate vaccine with a proprietary GSK adjuvant system. The vaccine will be administered to young male healthy subjects at 0, 1 and 6 months. The trial will assess the safety and immunogenicity of the candidate CMV vaccine. An additional secondary objective of this trial is to identify and validate a test which will be able to differentiate between previous CMV infection and CMV vaccination. Subjects will be followed for a total of 2 years.

Detailed Description
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The protocol posting has been amended to reflect changes as a consequence of an amendment to the protocol. The section impacted by the change is Key inclusion & exclusion criteria. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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A Phase I, Open-label, Vaccination Study to Evaluate the Safety and Immunogenicity of the GSK Biologicals Recombinant CMV gB Sub-unit Vaccine GSK1492903A in CMV-seronegative Healthy Male Adult Subjects

Conditions
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Infections, Cytomegalovirus

Intervention / Treatment
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* Biological: GSK Biologicals' Recombinant CMV gB Vaccine GSK1492903A


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. Male between, and including, 18 and 40 years of age at the time of the first vaccination. Written informed consent obtained from the subject. The subject consents to being informed of his CMV and HSV serostatus. Healthy subjects as established by medical history and clinical examination before entering into the study. Seronegative for CMV. Previously completed routine childhood vaccinations to the best of his knowledge. Exclusion Criteria: The HSV serologic status. 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 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Any chronic drug therapy to be continued during the study period. Receipt of live attenuated vaccines within 30 days of study vaccine administration. Receipt of medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) or allergy treatment with antigen injections within 14 days of study vaccine administration. Prior receipt of the adjuvant or any of its components being used in this study. Previous vaccination against CMV. History of recurrent herpes simplex infection (more than 1 episode per year). Any confirmed or suspected immunosuppressive or immunodeficient condition Hepatitis B infection or hepatitis C infection. A family history of congenital or hereditary immunodeficiency. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Major congenital defects or serious chronic illness including but not limited to diabetes mellitus and thyroid disease History of any neurologic disorders or seizures except people with febrile convulsions before the age of 5. History of malignancy Acute disease at the time of enrollment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests. Hepatomegaly, right upper quadrant abdominal pain or tenderness. Decreased renal function Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period. History of chronic alcohol consumption and/or drug abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Biological: GSK Biologicals' Recombinant CMV gB Vaccine GSK1492903A<br>* Intramuscular injection, 3 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence, intensity and relationship to vaccination of solicited local and general AEs. |  | During a 7 days follow-up after each vaccination | 
| Occurrence, intensity and relationship to vaccination of unsolicited AEs. |  | During a 31 days follow-up period after each vaccination | 
| Occurrence and relationship to vaccination of any SAEs. |  | Throughout the study period | 
| Haematological and biochemical parameters. |  | At months 0, 1, 2, 6, 7 12 and 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-gB antibody avidity in all groups; |  | At months 0, 1, 2, 6, 7 12 and 24 | 
| Neutralizing anti-cytomegalovirus (CMV) antibody response in all groups |  | At months 0, 1, 2, 6, 7, 12 and 24; | 
| Anti-CMV tegument proteins antibody response in all groups; |  | At months 0, 1, 2, 6, 7, 12 and 24; | 
| Frequencies of CD4/CD8 T-cells with antigen-specific IFN-g, IL-2, TNF-a and/or CD40L secretion/expression to gB as determined by ICS in all groups; |  | At months 0, 1, 2, 6, 7, 12 and 24 | 
| Anti-Herpes simplex virus (HSV) gD antibody response in all groups. |  | At months 0, 1, 2, 6, 7, 12 and 24 | 
| Anti-glycoprotein B (gB) antibody concentrations in all groups; |  | At months 0, 1, 2, 6, 7, 12 and 24; | 
| Anti-CMV Western Blot in all groups. |  | At months 0, 1, 2, 6, 7, 12 and 24 |