Study to Evaluate the Safety and Immunogenicity of an Investigational Pneumococcal Vaccine in the Elderly Population

Study Overview
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Brief Summary
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As the licensed pneumococcal vaccine is not always satisfactory in elderly, new investigational pneumococcal vaccines are evaluated in the healthy elderly population. Note: The study consists of the primary phase (106068): vaccination and follow-up and the extension (106072) of the primary phase: 1 year follow-up. This protocol posting details the procedures of both the primary & extension phase.

Detailed Description
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No new subjects will be enrolled in the Extension Phase of the study. All outcome measures at Month 12 will only be evaluated in the subjects in the Belgian site. Upon request, volunteers will receive flu vaccination free of charge. 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/II, Randomized, Observer Blinded Study to Evaluate and Compare the Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline Biologicals' Investigational Pneumococcal Vaccine Formulations Versus a Licensed Non-GlaxoSmithKline Biologicals' Vaccine and GlaxoSmithKline Biologicals' Aluminum-based 10-valent Pneumococcal Conjugate Vaccine, in Healthy Elderly Subjects

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: 11-valent pneumococcal vaccine GSK513026
* Biological: Pneumo 23™
* Biological: Placebo
* Biological: 10-valent pneumococcal vaccine GSK513026


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. A male or female between 65 and 85 years of age at the time of the first vaccination. Written informed consent obtained from the subject. Exclusion Criteria: Previous vaccination against Streptococcus pneumoniae. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory tests. Acute disease at the time of enrolment. History of documented radiologically confirmed pneumonia within 3 years prior to first vaccination. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s). Current or history of Parkinson disease, Alzheimer disease, stroke, dementia or any serious neurologic or mental disorders. All malignancies (excluding non-melanic skin cancer) and lymphoproliferative disorders diagnosed or treated actively during the past 5 years. Subjects with documented anaemia or iron-deficiency. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 3 months prior to the first vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol within 2 weeks of the first dose of vaccine(s) with the exception of a Flu vaccine which can be administered at least 1 week preceding the first dose of vaccine(s) or 1 month after the first dose of the vaccine(s). 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. Administration of immunoglobulins and/or any blood products within three months preceding the first dose of study vaccine or planned administration during the study period. History of administration of an experimental/licensed vaccine containing MPL or QS21. History of chronic alcohol consumption and/or drug abuse.

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 85 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br> | Biological: 11-valent pneumococcal vaccine GSK513026<br>* Two-dose intramuscular injection. Each group receiving one of the 3 formulations<br>|
| Experimental: Group B<br> | Biological: 11-valent pneumococcal vaccine GSK513026<br>* Two-dose intramuscular injection. Each group receiving one of the 3 formulations<br>|
| Experimental: Group C<br> | Biological: 11-valent pneumococcal vaccine GSK513026<br>* Two-dose intramuscular injection. Each group receiving one of the 3 formulations<br>|
| Active Comparator: Group D<br> | Biological: Pneumo 23™<br>* Single-dose intramuscular injection.<br>Biological: Placebo<br>* 1 intramuscular injection.<br>|
| Active Comparator: Group E<br> | Biological: 10-valent pneumococcal vaccine GSK513026<br>* Two-dose intramuscular injection<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 any solicited local and general signs and symptoms. |  | during a 7-day follow up period after each vaccine dose. | 
| Occurrence, intensity and relationship to vaccination of unsolicited local and general signs and symptoms |  | during a 31-day follow up period after each vaccine dose. | 
| Occurrence and relationship to vaccination of all serious adverse events (SAEs). |  | Throughout the study period. | 
| Post vaccination concentration IgG ≥5 µg/mL and fold increase Post/Pre ≥2 for at least 6 serotypes out of 11 |  | 1 month after Dose 2 in Groups A, B, C and 1 month after Dose 1 for Group D | 
| Post vaccination concentration and fold increase Post/Pre ≥2 for at least 6 serotypes out of 11, in Groups A through D. |  | One month after the first vaccine dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haematological and biochemical levels within or outside the normal ranges in all groups. |  | At Months 0, 1, 3, 4 and 12. | 
| IgG antibody concentrations to vaccine pneumococcal serotypes in all groups. |  | At Months 0, 1, 3, 4 and 12. | 
| Opsonophagocytic activity titres (OPA) against pneumococcal serotypes in all groups. |  | At Months 0, 1, 3, 4 and 12 | 
| Frequencies of IgG PS-specific plasma cells generated by in vitro cultivated memory B-cells for 4 serotypes in all groups, and for 11 serotypes in 10 subjects per group. |  | At Months 0, 1, 4 and 12. | 
| Anti-protein D, anti-tetanus and anti-diphtheria toxoids IgG antibody concentrations in Groups A, B, C and E. |  | At Months 0, 1, 3, 4 and 12. | 
| Frequencies of IgG carrier protein-specific plasma cells generated by in vitro cultivated memory B-cells in a subset of subjects (all subjects minus PS B-cell memory subset) of the Groups A, B, C and E. |  | At Months 0, 1, 4 and 12. | 
| Freq. of CD4+&CD8+ T cells with antigen-specific IL-2 &/or INFy &/or TNFa &/or CD40L secretion/expression to carrier protein as determined by ICS, in a subset of subjects (all subjects minus PS B-cell memory subset) of the Groups A, B, C and E. |  | At Months 0, 1, 4 and 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pneumonia, pneumococcal vaccine, elderly subjects, invasive pneumococcal diseases, Prophylaxis