Safety and Immunogenicity Study of GlaxoSmithKline (GSK) Biologicals' 10-valent Pneumococcal Conjugate Vaccine

Study Overview
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Brief Summary
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This study will evaluate safety, reactogenicity and immunogenicity of GSK Biologicals' pneumococcal conjugate vaccine compared to Prevenar™ when co-administered with DTPw-HBV/Hib and OPV or IPV vaccines, according to 2 different schedules: 6-10-14 weeks or 2-4-6 months of age. The study has 2 groups. One group of subjects will receive a 3-dose primary vaccination with the GSK Biologicals' pneumococcal conjugate vaccine (three different lots will be used and randomly allocated). The 2nd group of subjects will receive a 3-dose primary vaccination with Prevenar™. All children will receive concomitantly DTPw-HBV/Hib and OPV or IPV vaccines. This protocol posting deals with objectives & outcome measures of the primary study. The objectives & outcome measures of the Booster study are presented in a separate protocol posting (NCT number =00547248).

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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To Assess the Safety, Reactogenicity and Immunogenicity of GSK Biologicals' Pneumococcal Conjugate Vaccine Compared to Prevenar™, Co-administered With DTPw-HBV/Hib & OPV or IPV Vaccines as a 3-dose Primary Immunization Course During the First 6 Months of Age

Conditions
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Infections, Streptococcal

Intervention / Treatment
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* Biological: Pneumococcal conjugate vaccine GSK1024850A
* Biological: Prevenar
* Biological: Tritanrix-HepB
* Biological: Hiberix
* Biological: Polio Sabin.
* Biological: Poliorix.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between, and including, 6-12 weeks (42 to 90 days) of age at the time of the first vaccination. 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. Born after a gestation period between 36 and 42 weeks. Exclusion Criteria: 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. Planned administration/ administration of a vaccine not foreseen by the study protocol during the period starting one month before each dose of vaccine(s) and ending 7 days after dose 1 and dose 2 or 1 month after dose 3. Previous vaccination against diphtheria, tetanus, pertussis, polio, hepatitis B, Haemophilus influenzae type b, and/or S. pneumoniae with the exception of vaccines where the first dose can be given within the first two weeks of life according to the national recommendations History of or intercurrent diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b diseases. History of allergic disease or reactions likely to be exacerbated by any component of the vaccines. History of seizures (this criterion does not apply to subjects who have had a single, uncomplicated febrile convulsion in the past) or neurological disease. Acute disease at the time of enrolment Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical 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 active phase of the study.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synflorix 1 Group<br>Subjects aged 6-12 weeks from the Philippines receiving Synflorix™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ vaccines at 6, 10, 14 weeks of age. | Biological: Pneumococcal conjugate vaccine GSK1024850A<br>* 3 Intramuscular injections.<br>Biological: Tritanrix-HepB<br>* 3 Intramuscular injections<br>* Other names: DTPw-HBV;Biological: Hiberix<br>* Reconstituted with Tritanrix before injection<br>* Other names: Hib;Biological: Polio Sabin.<br>* 3 oral doses.<br>* Other names: OPV;Biological: Poliorix.<br>* 3 intramuscular injections<br>* Other names: IPV;|
| Experimental: Synflorix 2 Group<br>Subjects aged 6-12 weeks from Poland receiving Synflorix™ vaccine co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ vaccines at 2, 4, 6 months of age. | Biological: Pneumococcal conjugate vaccine GSK1024850A<br>* 3 Intramuscular injections.<br>Biological: Tritanrix-HepB<br>* 3 Intramuscular injections<br>* Other names: DTPw-HBV;Biological: Hiberix<br>* Reconstituted with Tritanrix before injection<br>* Other names: Hib;Biological: Polio Sabin.<br>* 3 oral doses.<br>* Other names: OPV;Biological: Poliorix.<br>* 3 intramuscular injections<br>* Other names: IPV;|
| Active Comparator: Prevenar 1 Group<br>Subjects aged 6-12 weeks from the Philippines receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Polio Sabin™ at 6, 10, 14 weeks of age. | Biological: Prevenar<br>* 3 Intramuscular injections<br>Biological: Tritanrix-HepB<br>* 3 Intramuscular injections<br>* Other names: DTPw-HBV;Biological: Hiberix<br>* Reconstituted with Tritanrix before injection<br>* Other names: Hib;Biological: Polio Sabin.<br>* 3 oral doses.<br>* Other names: OPV;Biological: Poliorix.<br>* 3 intramuscular injections<br>* Other names: IPV;|
| Active Comparator: Prevenar 2 Group<br>Subjects aged 6-12 weeks from Poland receiving the Prevenar™ vaccine, co-administered with Tritanrix™-HepB/Hiberix™ and Poliorix™ at 2, 4, 6 months of age. | Biological: Prevenar<br>* 3 Intramuscular injections<br>Biological: Tritanrix-HepB<br>* 3 Intramuscular injections<br>* Other names: DTPw-HBV;Biological: Hiberix<br>* Reconstituted with Tritanrix before injection<br>* Other names: Hib;Biological: Polio Sabin.<br>* 3 oral doses.<br>* Other names: OPV;Biological: Poliorix.<br>* 3 intramuscular injections<br>* Other names: IPV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Rectal Temperature Above (>) 39.0 Degrees Celsius (°C) | Fever was measured as rectal temperature. Assessment of occurrences of fever > 39.0 °C was performed post doses 1, 2 and 3 and across doses of Synflorix™ or Prevenar™ vaccine. | Within 4 day (Days 0-3) after each dose and across doses | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any and Any 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. | Within 4 day (Days 0-3) after each dose and across doses | 
| Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms | Solicited general symptoms assessed include drowsiness, fever (defined as rectal temperature ≥ 38.0°C), irritability, and loss of appetite. Grade 3 (G3) drowsiness was defined as drowsiness which prevented normal everyday activities. Grade 3 (G3) fever was defined as fever (rectal temperature) above (>) 40.0 degree Celsius (°C). Grade 3 (G3) irritability was defined as crying that could not be comforted/preventing normal activity. Grade 3 (G3) loss of appetite was defined as the subject not eating at all. Any is defined as incidence of the specified symptom regardless of intensity or relationship to study vaccination. Related (REL) = Symptom assessed by the investigator as causally related to vaccination. | Within 4-day (Days 0-3) after each dose and across doses | 
| 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. | Within 31 days (Days 0-30) after each vaccination | 
| Number of Subjects With Serious Adverse Events (SAEs) | Serious adverse events (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 Active Phase: From Month 0 to Month 3 for Synflorix 1 Group and Prevenar 1 Group and from Month 0 to Month 5 for the Synflorix 2 Group and Prevenar 2 Group | 
| Number of Subjects With Serious Adverse (SAEs) | Serious adverse events (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 Extended Safety Follow-Up Phase: At Month 8 for Synflorix 1 Group and Prevenar 1 Group and at Month 10 for the Synflorix 2 Group and Prevenar 2 Group | 
| Concentrations of Antibodies Against Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F | Seropositivity status, defined as Anti-pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F antibody concentrations ≥ 0.05 microgram per milliliter (µg/mL). | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations Equal to or Above (≥) 0.2 Microgram Per Milliliter (µg/mL) | Cut-off values assessed were greater than or equal to 0.2 microgram per milliliter (µg/mL) in the sera of subjects. | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Number of Subjects With Anti-pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Antibody Concentrations Equal to or Above (≥) 0.05 Microgram Per Liter (µg/mL) | Cut-off values assessed were greater than or equal to 0.05 microgram per liter (µg/mL) in the sera of subjects. | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F ≥ 8 | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Number of Subjects With Opsonophagocytic Activity (OPA) Against Vaccine Pneumococcal Serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F Equal to or Above (≥) 8 | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C , 19F and 23F ≥ 8. | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Seropositivity status, defined as Anti-pneumococcal cross-reactive serotypes 6A and 19A antibody concentrations ≥ 0.05 microgram per milliliter (µg/mL). | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Number of Subjects With Concentrations of Antibodies Against Cross-reactive Pneumococcal Serotypes 6A and 19A Equal to or Above (≥) 0.05 Microgram Per Milliliter (μg/mL) | Cut-off values assessed were greater than or equal to 0.05 microgram per milliliter (μg/mL) in the sera of subjects seronegative before vaccination. | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes 6A and 19A | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8 | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Number of Subjects With Opsonophagocytic Activity (OPA) Against Cross-reactive Pneumococcal Serotypes 6A and 19A Equal to or Above (≥) 8 | Seropositivity status, defined as Opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A ≥ 8 | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Concentrations of Antibodies Against Protein D (Anti-PD) | Seropositivity status, defined as Anti-PD antibody concentrations ≥ 100 ELISA units per milliliter ( EL.U/mL) | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Number of Subjects With Concentrations of Antibodies Against Protein D (Anti-PD) Equal to or Above (≥) 100 ELISA Units Per Milliliter (EL.U/mL) | Cut-off values assessed were greater than or equal to 100 ELISA units per milliliter (EL.U/mL) in the sera of subjects. | One month after the administration of the 3rd vaccine dose of Synflorix™ and Prevenar™ | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 0.15 Microgram Per Milliliter (µg/ mL) | Cut-off values assessed were greater than or equal to 0.15 microgram per milliliter (µg/ mL) in the sera of subjects. | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Number of Subjects With Anti-polyribosyl-ribitol Phosphate (Anti-PRP) Antibody Concentration Equal to or Above 1.0 Microgram Per Milliliter (µg/mL) | Cut-off values assessed were greater than or equal to 1.0 microgram per milliliter (µg/mL) in the sera of subjects. | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Anti-polyribosyl-ribitol-phosphate (Anti-PRP) Antibody Concentrations | Seroprotection status, defined as Anti-PRP antibody concentrations ≥ 0.15 µg/mL and ≥ 1.0 µg/mL | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Number of Subjects With Anti-diphtheria (Anti D) and Anti-tetanus Toxoids (Anti TT) Antibody Concentrations Equal to or Above 0.1 International Units Per Milliliter (IU/mL) | Cut-off values assessed were greater than or equal to 0.1 International Units per milliliter (IU/mL) in the sera of subjects. | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Anti-diphtheria (Anti-D) and Anti-tetanus Toxoids (Anti-TT) Antibody Concentrations | Seroprotection status, defined as Anti-diphtheria toxoid or anti-tetanus toxoid antibody concentrations ≥ 0.1 IU/mL | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Number of Subjects With Anti-Hepatitis B Surface Antigen (HBs) Antibody Concentrations Equal to or Above 10 Milli-International Units Per Milliliter (mIU/mL) | Cut-off values assessed were greater than or equal to 10 milli-International Units per milliliter (mIU/mL) in the sera of subjects. | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Anti-hepatitis B Surface Antigen (HBs) Antibody Concentrations | Seroprotection status, defined as Anti-HBs antibody concentrations ≥ 10 mIU/mL | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Number of Subjects With Anti-polio Type 1, 2 and 3 Antibody Titers Equal to or Above (≥) 8 | Titers were expressed as geometric mean titres (GMTs). | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Anti-polio Type 1, 2 and 3 (Anti-Polio 1, 2 and 3) Antibody Titers | Seroprotection status, defined as Anti-polio type 1, Anti-polio type 2 and Anti-polio type 3 antibody titers ≥ 8 | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Number of Subjects With Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations Equal to or Above 15 ELISA Unit Per Milli-liter (EL.U/mL) (Seropositivity) | Cut-off values assessed were greater than or equal to 15 ELISA unit per milli-liter (EL.U/mL) in the sera of subjects seronegative before vaccination. | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Anti-Bordetella Pertussis (Anti-BPT) Antibody Concentrations | Seropositivity status, defined as Anti-BPT antibody concentrations ≥ 15 EL.U/mL. | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 
| Number of Subjects With Vaccine Response to Bordetella Pertussis | Vaccine response to B. pertussis;defined as appearance of antibodies in subjects initially seronegative (S-) (i.e., concentrations < 15 EL.U/mL) or at least maintenance of pre-vaccination antibody concentrations in subjects who were initially seropositive (S+) (i.e., with concentrations ≥ 15 EL.U/mL). | One month after the administration of the 3rd vaccine dose of Tritanrix™-HepB/Hiberix™ + Polio Sabin™ or Poliorix™ | 

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