Safety & Immunogenicity of Pneumococcal Vaccine 2189242A in Children Aged 12-23 Months at the Time of First Vaccination

Study Overview
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Brief Summary
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This study will assess the safety, reactogenicity and immunogenicity of different formulations of GSK Biologicals' pneumococcal vaccine 2189242A when administered alone or in combination with the 10-valent pneumococcal conjugate vaccine (GSK1024850A vaccine) as a 2-dose primary vaccination course followed by a booster dose in healthy children aged 12-23 months at the time of first vaccination. Considering that febrile reactions are frequently observed following pneumococcal vaccination, usually co-administered with other routine paediatric vaccines, the primary study objective will focus on evaluating the increase in grade 3 fever (i.e. rectal temperature >40.0°C).

Official Title
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Safety, Reactogenicity and Immunogenicity of GlaxoSmithKline (GSK) Biologicals' Investigational Vaccination Regimen in Children Aged 12-23 Months at the Time of First Vaccination.

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal vaccine GSK2189242A (formulation 1)
* Biological: Pneumococcal vaccine GSK2189242A (formulation 2)
* Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 3)
* Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 4)
* Biological: Pneumococcal vaccine GSK1024850A


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parent(s)/Legally Acceptable Representative(s) (LAR) can and will comply with the requirements of the protocol Male or female between, and including, 12 and 23 months of age at the time of the first vaccination. Written informed consent obtained from the parents/LAR(s) of the subject. Healthy subjects as established by medical history and clinical examination before entering into the study. Exclusion Criteria: Use of any investigational or non-registered product 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 of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Planned administration/administration of a vaccine not foreseen by the study protocol during the study period starting from 30 days before each dose and ending 30 days after each dose of vaccine(s). Previous vaccination against S. pneumoniae since birth. History of any hypersensitivity reaction following any previous vaccination. Eczema and any history of allergy Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required), including human immunodeficiency virus infection. A family history of congenital or hereditary immunodeficiency. Major congenital defects or any chronic illness. History of any neurologic disorders or seizures. Acute disease and/or fever at the time of enrolment. Fever is defined as temperature >= 37.5°C on oral or axillary setting, or >= 38.0°C on rectal setting. Subjects with a minor illness without fever may be enrolled at the discretion of the investigator. Administration of immunoglobulins and/ or any blood products within the 3 months preceding the first dose of study vaccine or planned use during the study period. Child in care.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 23 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br> | Biological: Pneumococcal vaccine GSK2189242A (formulation 1)<br>* Three doses will be administered intramuscularly, at Month 0, 2 and 6.<br>|
| Experimental: Group 2<br> | Biological: Pneumococcal vaccine GSK2189242A (formulation 2)<br>* Three doses will be administered intramuscularly, at Month 0, 2 and 6<br>|
| Experimental: Group 3<br> | Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 3)<br>* Three doses will be administered intramuscularly, at Month 0, 2 and 6<br>|
| Experimental: Group 4<br> | Biological: Pneumococcal vaccine GSK2189242A combined with pneumococcal vaccine GSK1024850A (formulation 4)<br>* Three doses will be administered intramuscularly, at Month 0, 2 and 6<br>|
| Experimental: Control Group<br> | Biological: Pneumococcal vaccine GSK1024850A<br>* Three doses will be administered intramuscularly, at Month 0, 2 and 6<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Fever > 40.0°C (Rectal Temperature) | The number of subjects with rectal temperature higher (>) than 40.0 degrees Celsius (°C) is reported. | Within 7 days (Day 0-Day 6) following at least one dose of the primary vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Any and Grade 3 Solicited Local Symptoms | Solicited local symptoms assessed include pain, redness and swelling. Grade 3 pain was defined as crying when limb was moved/spontaneously painful. Grade 3 swelling/redness was defined as swelling/redness larger than (>) 30 millimeters (mm). Any is defined as incidence of the specified symptom regardless of intensity. | During the 7-day (Days 0-6) post-vaccination period following each dose (Dose 1, Dose 2 and Booster dose) | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed include drowsiness, fever (defined as rectally temperature ≥ 38.0°C), irritability, and loss of appetite. Grade 3 drowsiness = drowsiness which prevented normal everyday activities. Grade 3 fever was defined as fever (rectally temperature) above (>) 40.0 degree Celsius (°C). Grade 3 irritability = crying that could not be comforted/preventing normal activity. Grade 3 loss of appetite = not eating at all. Any is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. | During the 7-day (Days 0-6) post-vaccination period following each dose (Dose 1, Dose 2, Booster dose) | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An AE 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. Any is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. | During the 31-day (Days 0-30) follow-up period after each primary dose | 
| Number of Subjects With Unsolicited Adverse Events (AEs) | An AE 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. Any is defined an incidence of an unsolicited AE regardless of intensity or relationship to study vaccination. | During the 31-day (Days 0-30) follow-up period after the booster dose | 
| Number of Subjects With Serious Adverse Events (SAEs) | SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. | During the entire study period starting at the administration of the first vaccine dose up to study end (from Day 0 up to Month 7) | 
| Anti-pneumococcal dPly and PhtD Proteins Antibody Concentrations | Seropositivity status, defined as anti-pneumococcal dPly antibody concentrations ≥ 599 Luminex Units per milliliter (LU/mL) and anti-pneumococcal PhtD antibody concentrations ≥ 391 LU/mL. | One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7) | 
| Anti-pneumococcal Serotypes and Cross-reactive Serotypes Antibody Concentrations | Seropositivity status, defined as anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and cross-reactive serotype 6A and 19 antibody concentrations ≥ 0.05 microgram per milliliter (µg/mL). | One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7) | 
| Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes and Cross-reactive Serotypes | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F and cross-reactive serotypes 6A and 19A ≥ 8. | One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7) | 
| Antibody Concentrations to Protein D (Anti-PD) | Seropositivity status, defined as anti-PD antibody concentrations ≥ 112 Luminex Units per milliliter (LU/mL). | One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7) | 
| Level of Anti-dPly Antibodies Inhibiting Ply Haemolysis Activity | Inhibition of haemolysis activity of pneumolysin (Ply) by anti-dPly antibodies was measured in vitro by mean of a haemolytic assay. The haemolysis activity could be followed by measuring the level of haemoglobin released. Anti-dPly titers (for inhibition of haemolytic activity) ≥ 140. | One month post-dose 2 (Month 3), prior to the booster dose (Month 6) and one month post-booster (Month 7) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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toddlers, immunogenicity, Pneumococcal vaccine, Haemophilus influenzae, safety, Streptococcus pneumoniae, Streptococcus Pneumoniae Vaccines