Safety & Immunogenicity Study of 10-Valent Pneumococcal Conjugate Vaccine When Administered as a 2-Dose Schedule

Study Overview
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Brief Summary
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Assess immuno, reacto of the 10-valent pneumococcal vaccine after 2 doses (2, 4 months of age) and after the complete 2, 4, 11 months schedule when co-administered with DTPa-HBV-IPV/Hib or DTPa-IPV/Hib (according to national recommendations)

Detailed Description
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Total anticipated: 300 subjects (150/group). 2-dose group - 10-valent pneumococcal vaccine + DTPa combined vaccine (2, 4, 11 months); Comparator group - 10-valent pneumococcal vaccine (2, 3, 4, 11 months) + DTPa combined vaccine (2, 4, 11 months). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Official Title
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An Open, Randomized, Phase IIIa Study to Evaluate the Safety and Immunogenicity of GSK Biologicals' 10-valent Pneumococcal Conjugate Vaccine, When Administered Intramuscularly According to a 2-4-11 Months Vaccination Schedule

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: GSK Biologicals' 10-valent pneumococcal conjugate vaccine.
* Biological: Infanrix hexa.
* Biological: Infanrix-IPV/Hib.


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. A male or female between, and including, 8 and 16 weeks (56-120 days) of age at the time of the first vaccination. 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. Born after a gestation period of 36 to 42 weeks. Exclusion criteria: Use of any investigational or non-registered 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. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting 30 days before the first dose of vaccine(s) and ending 30 days after the last dose, with exception of BCG vaccination which can be given after the 1 month post-dose 2 or 3 (2-4-11 or 2-3-4-11 months of age schedule) blood sampling and a minimum of 30 days before the pre-booster dose blood sampling. Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, and/or S. pneumoniae. History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, Haemophilus influenzae type b disease, and/or invasive pneumococcal diseases. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of any neurologic disorders or seizures. Acute disease at the time of enrolment. Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs since birth. 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 since birth or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 8 Weeks
Maximum Age: 16 Weeks

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2-dose group<br>Subjects receiving GSK Biologicals' 10-valent pneumococcal conjugate vaccine at 2-4-11 months of age, co-administered with DTPa-combined vaccine (Infanrix hexa or Infanrix IPV/Hib) at 2-4-11 months of age. | Biological: GSK Biologicals' 10-valent pneumococcal conjugate vaccine.<br>* Intramuscular injection, 3 or 4 doses (2-4-11 or 2-3-4-11 months of age schedule).<br>Biological: Infanrix hexa.<br>* Intramuscular injection, 3 doses (2-4-11 months of age schedule).<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Infanrix-IPV/Hib.<br>* Intramuscular injection, 3 doses (2-4-11 months of age schedule).<br>* Other names: DTPa-IPV/Hib;|
| Experimental: Comparator group<br>Subjects receiving GSK Biologicals' 10-valent pneumococcal conjugate vaccine at 2-3-4-11 months of age, co-administered with DTPa-combined vaccine (Infanrix hexa or Infanrix IPV/Hib) at 2-4-11 months of age. | Biological: GSK Biologicals' 10-valent pneumococcal conjugate vaccine.<br>* Intramuscular injection, 3 or 4 doses (2-4-11 or 2-3-4-11 months of age schedule).<br>Biological: Infanrix hexa.<br>* Intramuscular injection, 3 doses (2-4-11 months of age schedule).<br>* Other names: DTPa-HBV-IPV/Hib;Biological: Infanrix-IPV/Hib.<br>* Intramuscular injection, 3 doses (2-4-11 months of age schedule).<br>* Other names: DTPa-IPV/Hib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Pneumococcal Serotypes | A seroprotected subject was defined as a subject who had anti-pneumococcal serotypes antibody concentrations greater than or equal to (≥) the threshold value of 0.20 micrograms per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C,19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs). The results presented for the Group 1 correspond to the primary outcome. | One month post-dose 2 (Month 3) administration of Synflorix™ vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroprotected Subjects Against Pneumococcal Serotypes | A seroprotected subject was defined as a subject who had anti-pneumococcal serotypes antibody concentrations greater than or equal to (≥) the threshold value of 0.20 micrograms per milliliter (μg/mL). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C,19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs). | One month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine | 
| Antibody Concentrations Against Pneumococcal Serotypes | The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C,19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F enzyme-linked immunosorbent assay (ELISA), expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (μg/mL). The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. This outcome concerns results for the Primary and Booster Phases of the study. | One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine | 
| Opsonophagocytic Activity Against Vaccine Pneumococcal Serotypes | Seropositivity status was defined as the opsonophacocytic activity against pneumococcal serotypes greater than or egual to (≥) the value of 8. The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C,19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F).This outcome concerns results for the Primary and Booster Phases of the study. | One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine | 
| Antibody Concentrations Against Protein D (Anti-PD) | Anti-protein D concentrations are expressed as geometric mean concentrations (GMCs), in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL).Seropositivity status was defined as Anti-PD antibody concentrations greater than or equal to (≥) the value of 100 EL.U/mL. This outcome concerns results for the Primary and Booster Phases of the study. | One month post-dose 2 or post-dose 3 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine | 
| Antibody Concentrations Against Diphteria (Anti-D) and Tetanus (Anti-T) Toxoids | Concentrations of antibodies are presented as geometric mean concentrations, expressed as international units per milliliter (IU/mL). Seroprotection status was defined as anti-diphteria and anti-tetanus toxoid antibody concentrations greater than or equal to (≥) the value of 0.1 IU/mL. This outcome concerns results for the Primary and Booster Phases of the study. | One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine | 
| Antibody Concentrations Against Polyribosyl Ribitol Phosphate (Anti-PRP) | Concentrations of antibodies are presented as geometric mean concentrations, expressed as micrograms per milliliter (μg/mL). Seroprotection status was defined as anti-polyribosyl ribitol phosphate (Anti-PRP) antibody concentrations greater than or equal to (≥) the cut-off values of 0.15 μg/mL and ≥ 1.0 μg/mL. This outcome concerns results for the Primary and Booster Phases of the study. | One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) booster dose of Synflorix™ vaccine | 
| Antibody Concentrations Against Pertussis Toxoid (Anti-PT), Filamentous Haemagglutinin (Anti-FHA) and Pertactin (Anti-PRN) | Concentrations of antibodies are presented as geometric mean concentrations, expressed as enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL). Seropositivity status was defined as anti-pertussis toxoid (Anti-PT), anti-filamentous haemagglutinin (Anti-FHA) and anti-pertactin (Anti-PRN) antibody concentrations greater than or equal to (≥) the cut-off value of 5 EL.U/mL. This outcome concerns results for the Primary and Booster Phases of the study. | One month post-dose 2 (Month 3) administration, one month before (Month 9) and after (Month 10) the booster dose of Synflorix™ vaccine | 
| Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) | Concentrations of antibodies are presented as geometric mean concentrations, expressed as milli international units per milliliter (mIU/mL). Seroprotection status was defined as anti-hepatitis B surface antigen (anti-HBs) antibody concentrations greater than or equal to (≥) the cut-off value of 10 mIU/mL. This outcome concerns results for the Primary and Booster Phases of the study and included only the subset of subjects who received Infanrix Hexa™ as the co-administered vaccine. | One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine | 
| Antibody Titers Against Polio Type 1, 2 and 3 (Anti-polio 1, 2 and 3) | Titers of antibodies are presented as geometric mean titers. Seroprotection status was defined as anti-polio types 1, 2 and 3 (Anti-polio 1, 2 and 3) antibody titers greater than or equal to (≥) the value of 8. This outcome concerns results for the Primary and Booster Phases of the study and included only the subset of subjects who received Infanrix Hexa™ as the co-administered vaccine. | One month post-dose 2 (Month 3) administration, one month before (Month 9) and one month after (Month 10) the booster dose of Synflorix™ vaccine | 
| Number of Subjects With Booster Vaccine Response to Anti-PT, Anti-FHA and Anti-PRN Antibodies | Booster vaccine response to pertussis toxoid (PT), filamentous haemagglutinin (FHA) and pertactin (PRN), defined as the appearance of antibodies in subjects who were seronegative (Pre-booster status S-) (i.e., with antibody concentrations < 5 EL.U/mL) just before booster dose, and at least two-fold increase of pre-vaccination antibody concentrations in those who were seropositive (Pre-booster status S+) (i.e., with antibody concentrations ≥ 5 EL.U/mL) just before booster dose. | One month after (Month 9) the administration of the booster dose of Synflorix™ vaccine | 
| Number of Subjects With Any and Grade 3 Solicited Local Symptoms | Assessed local symptoms were pain, redness and swelling. Any = Occurrence of the specified solicited local symptom, regardless of intensity. Grade 3 Pain = Crying when limb was moved/spontaneously painful. Grade 3 Redness/Swelling = Redness/swelling at injection site larger than (>) 30 millimeters (mm). Across doses= across the 2 doses of the Synflorix™ vaccine in the Synflorix I group and across the 3 doses of the Synflorix™ vaccine in the Synflorix II group. | During the 4-day (Days 0-3) period following the primary vaccination (across doses) and during the 4-day (Days 0-3) period following the booster vaccination (post Booster) with the Synflorix™ vaccine | 
| Number of Subjects With Solicited General Symptoms | Assessed solicited general symptoms were drowsiness, irritability/fussiness (Irr./Fuss.), loss of appetite (Loss Appet.) and fever (rectal temperature higher than [≥] 38.0 degrees Celsius [°C]). Any = Occurrence of the specified solicited general symptom, regardless of intensity or relationship to vaccination. Related = Occurrence of the specified symptom assessed by the investigators as causally related to vaccination. Grade 3 Drowsiness = Drowsiness that prevented normal activity. Grade 3 Irr./Fuss. = Crying that could not be comforted/prevented normal activity. Grade 3 Loss of appetite = Subject did not eat at all. Grade 3 Fever = Rectal temperature higher than (>) 40.0°C. Across doses= across the 2 doses of the Synflorix™ vaccine in the Synflorix I group and across the 3 doses of the Synflorix™ vaccine in the Synflorix II group. | During the 4-day (Days 0-3) period following the primary vaccination (across doses) and during the 4-day (Days 0-3) period following the booster vaccination (post Booster) with the Synflorix™ vaccine | 
| Number of Subjects With Unsolicited Adverse Events | An unsolicited AE was defined as 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination. | Within the 31-day (Days 0-30) post-primary vaccination period, across doses | 
| Number of Subjects With Unsolicited Adverse Events | An unsolicited AE was defined as 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. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For the marketed products administered in the study, this also included failure to produce expected benefits (i.e. lack of efficacy), abuse or misuse of the product. Any = Occurrence of an unsolicited AE, regardless of intensity or relationship to vaccination. | Within the 31-day (Days 0-30) post booster vaccination period | 
| Number of Subjects With Serious Adverse Events | A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination. | During the primary vaccination period | 
| Number of Subjects With Serious Adverse Events | A SAE was defined as any medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity in a subject. AE(s) considered as SAE(s) also included invasive or malignant cancers, intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that did not result in hospitalisation, as per the medical or scientific judgement of the physician. Any = Occurrence of a SAE, regardless of relationship to vaccination. | During the booster vaccination period | 

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