Assess Reacto- and Immunogenicity of Pneumococcal Conjugate Vaccine When Given as Booster or a 2 Dose Catch up Schedule

Study Overview
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Brief Summary
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This is a booster study in 2 groups of healthy children less than 3 years old to measure the reactogenicity, safety and immunogenicity of GSK Biologicals' pneumococcal conjugate vaccine, when given as a booster or as a two-dose catch-up vaccination. This protocol posting deals with objectives and outcome measures of the booster phase. The objectives and outcome measures of the primary phase are presented in a separate protocol posting (NCT number = NCT00338351).

Detailed Description
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The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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Phase II, Observer-blind Follow-up Study to Assess reacto-and Immunogenicity of GSK Biologicals' Pneumococcal Conjugate Vaccine (GSK1024850A), When Given as Booster in Primed Children or as 2-dose Catch-up in Unprimed Children.

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Synflorix
* Biological: Infanrix Hexa
* Biological: Havrix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between, and including, 18-21 months of age at the time of vaccination. Subjects who previously participated in the primary study and received 3 doses of study or control vaccines during the primary study. Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. Written informed consent obtained from the parent or guardian of 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 drug or vaccine other than the study vaccine(s) within 30 days preceding the booster doses of study vaccines, or planned use during the study period (active phase and extended safety follow-up). Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month (30 days) before the booster doses of vaccine(s) and during the active phase of the study (up to the follow-up visit (Visit 3)). History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of seizures (subjects who have had a single, uncomplicated febrile convulsion in the past can be included) or progressive neurological disease. Acute disease at the time of enrolment. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the booster doses of study vaccines. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination. A family history of congenital or hereditary immunodeficiency. Major congenital defects or serious chronic illness. Administration of immunoglobulins and/or any blood products within the last 3 months prior to booster or follow-up vaccination or planned administration during the active phase of the study.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 21 Months

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix Booster Group<br>Subjects previously primed with Synflorix™ and receiving in the current study Havrix™ co-administered with Infanrix™ hexa (Dose 1) and Synflorix™ (Dose 2). | Biological: Synflorix<br>* Intramuscular injection, 1 or 2 doses<br>Biological: Infanrix Hexa<br>* 1 Intramuscular injection<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Havrix<br>* 1 Intramuscular injection<br>|
| Experimental: Synflorix Catch-up Group<br>Subjects previously primed with Havrix™ co-administered with Infanrix™ hexa and receiving in the current study Synflorix™ co-administered with Infanrix™ hexa (Dose 1) and Synflorix™ (Dose 2). | Biological: Synflorix<br>* Intramuscular injection, 1 or 2 doses<br>Biological: Infanrix Hexa<br>* 1 Intramuscular injection<br>* Other names: DTPa-HBV-IPV/Hib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Grade 3 Symptoms (Solicited and Unsolicited) | Grade 3 symptoms are symptoms which prevent normal, everyday activities (e.g. in a young child such symptom would prevent attendance at school/ kindergarten/ a day-care center and would cause the parents/guardians to seek medical advice). | Within 4 days after the administration of any study vaccine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. | Within 4 days after the administration of any study vaccine dose | 
| Number of Subjects Reporting Solicited General Symptoms | Solicited general symptoms assessed include drowsiness, fever, irritability and loss of appetite. Fever was defined as rectal temperature ≥ 38 degrees Celsius. | Within 4 days after the administration of any study vaccine dose | 
| Number of Subjects Reporting Unsolicited Adverse Events | An Adverse Event is 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. | Within 31 days after the administration of any study vaccine dose | 
| Number of Subjects Reporting Serious Adverse Events During the Active Phase of the Study | A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | Throughout the active phase of the study ( from the beginning of the booster phase up to 1 month after the second booster dose) | 
| Number of Subjects Reporting Serious Adverse Events Throughout the Entire Study Period | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | Throughout the entire study period (from the beginning of the booster phase up to the end of the 6-month extended safety follow-up) | 
| Number of Subjects With Vaccine Pneumococcal Serotype Antibody Concentrations Above the Cut-off Value | Anti-pneumococcal antibody cut-off value assessed was 0.20 microgram per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. | Before (pre) and one month after (post) the administration of Dose 2 | 
| Number of Subjects With Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes Above the Cut-off Value | Cut-off value for opsonophagocytic activity against pneumococcal antibody assessed was ≥ 8 The vaccine pneumococcal serotypes assessed include 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F. | Before (pre) and one month after (post) the administration of Dose 2 | 
| Number of Subjects With Anti-protein D Antibody Concentrations Above the Cut-off Value | Anti-protein D antibody cut-off value assessed was ≥ 100 Enzyme-Linked Immuno Sorbent Assay (ELISA) unit per milliliter (EL.U/mL). | Before (pre) and one month after (post) the administration of Dose 2 | 
| Anti-hepatitis A Virus Antibodies Concentration | Concentration of anti-hepatitis A antibodies given as geometric mean concentration (GMC) in milli-international units per milliliter (mIU/mL). | Before (pre) and one month after (post) the administration of Dose 2 | 
| Number of Subjects With Anti-hepatitis A Antibody Concentrations Above the Cut-off Value | Anti-hepatitis A antibodies cut-off value assessed was ≥ 15 mIU/mL. | Before (pre) and one month after (post) the administration of Dose 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Pneumococcal disease, Safety, Booster vaccination, Pneumococcal vaccine